General Neurology

(Contributed by Dr. Jonathan Trobe.)

(Source: Courtesy of ZEISS Microscopy, Jena, Germany. Creative Commons Attribution-Share Alike 2.0 Generic [CC BY] license, creativecommons.org/licenses/by-sa/2.0/deed.en.)

(Source: Wikimedia Commons. Public domain.)

In the mammalian nose, odorants are detected by odorant receptors (ORs) in a combinatorial fashion: one odorant can activate multiple odorant receptors, and each odorant receptor can detect more than one odorant. (a) When the combinatorial code was first established, each odorant receptor was tested against a given concentration of a single odorant, and only agonist interactions were analyzed. (b) Recent studies that analyzed the responses of odorant receptors to specific odorants presented as part of odor mixtures found that odorants, in addition to their agonist role, can also serve as modulators (antagonists, inverse agonists, partial agonists, and synergistic ligands) to odorant receptor activity. A “No odorant” condition depicts the activation profile of odorant receptors 1 to 6 in the absence of any odorant. Note: An inverse agonist binds to the same receptor as an agonist but brings about the opposite response to that of an agonist, whereas an antagonist binding to such a receptor will disrupt the interaction and the function of both the agonist and the inverse agonist at the receptor. (Source: Kurian SM, Naressi RG, Manoel D, Barwich AS, Malnic B, Saraiva LR. Odor coding in the mammalian olfactory epithelium. Cell Tissue Res 2021;383[1]:445-56. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

Recent single-cell RNA-sequencing experiments showed that most intact odorant receptors (ORs) are expressed in the olfactory epithelium across a large dynamic range, with only a minority being expressed at very high levels. As measured by single-cell RNA-sequencing, the abundance level of a given odorant receptor in the olfactory epithelium correlates perfectly with the number of olfactory sensory neurons expressing it. The arrow depicts the position of the last odorant receptors plotted. (Source: Kurian SM, Naressi RG, Manoel D, Barwich AS, Malnic B, Saraiva LR. Odor coding in the mammalian olfactory epithelium. Cell Tissue Res 2021;383[1]:445-56. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

In the nose, each mature olfactory sensory neuron (mOSN) expresses one allele of a single odorant receptor (OR) gene. This type of expression became known in the field as the "one neuron - one receptor" rule. (Source: Kurian SM, Naressi RG, Manoel D, Barwich AS, Malnic B, Saraiva LR. Odor coding in the mammalian olfactory epithelium. Cell Tissue Res 2021;383[1]:445-56. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

Expression patterns of odorant receptors in the olfactory epithelium. In the nose, mature olfactory sensory neurons expressing the same odorant receptors gene are stochastically distributed within a spatially restricted area of the olfactory epithelium, also known as a “zone.” Early studies identified four nonoverlapping odorant receptor expression zones, but later studies identified as many as nine to 12 partially overlapping zones. In the schematic, the four nonoverlapping odorant receptor expression zones (blue, red, yellow, and green colors) are shown: left panel, lateral view of the olfactory mucosa; right panel, a coronal section of the olfactory mucosa (including the respiratory epithelium, in grey). (Source: Kurian SM, Naressi RG, Manoel D, Barwich AS, Malnic B, Saraiva LR. Odor coding in the mammalian olfactory epithelium. Cell Tissue Res 2021;383[1]:445-56. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

The major cell types of the mammalian olfactory mucosa. In mammals, the olfactory mucosa is composed of the olfactory epithelium and a submucosa. The olfactory epithelium is a pseudostratified epithelium composed mainly of sustentacular cells (SUCs), globose basal cells (GBCs), horizontal globose cells (HBCs), immature olfactory sensory neurons (iOSNs), and mature olfactory sensory neurons (mOSNs). The olfactory ensheathing cells (OECs) are an important cell type populating the submucosa. (Source: Kurian SM, Naressi RG, Manoel D, Barwich AS, Malnic B, Saraiva LR. Odor coding in the mammalian olfactory epithelium. Cell Tissue Res 2021;383[1]:445-56. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

Each olfactory receptor neuron expresses one olfactory receptor, which responds to different odorants. Odorant molecules bind to olfactory receptors on cilia. Olfactory receptors activate olfactory receptor neurons, which transduce the input signal into action potentials. Glomeruli generally receive input from olfactory receptors of one specific type and connect to the principal neurons of the olfactory bulb and mitral and tufted cells. Legend: (MT) mitral/tufted. (OB) Olfactory bulb. (OR) Olfactory receptors. (ORN) Olfactory receptor neuron (also called OSN, olfactory sensory neuron). (Source: Wikimedia Commons, derived from: Auffarth B, Kaplan B, Lansner A. Map formation in the olfactory bulb by axon guidance of olfactory neurons. Front Syst Neurosci 2011;5:84. Creative Commons Attribution 3.0 Unported [CC BY 3.0] license, creativecommons.org/licenses/by/3.0/deed.en.)

Cajal drawing showing the olfactory cortex layers. Legend: (A) Olfactory fibers layer. (B) Plexiform layer. (C) Layer of polymorphic superficial cells. (D) Layer of the pyramids. (E) Deep polymorphous cells. (b) Bifurcation of axons. (Source: Ramón y Cajal S. Estudios sobre la corteza cerebral humana. IV. Estructura de la corteza cerebral olfativa del hombre y mamíferos. Trab Lab Invest Biol 1901;1:1-140. Instituto Cajal, Madrid, Spain. See: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Olig2 (oligodendrocyte progenitors, red), S100β (astrocytes, green), and myelin binding protein (MBP, gray). Nuclei labeled with Hoechst (blue). (Source: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Cajal drawing of an olfactory bulb section of a month-old rat. Weigert-Pal method. Legend: (A) Layer of the glomeruli. (B) Lower molecular layer. (C) Mitral layer. (D) Higher molecular layer. (E) Coating the grains. (a) Myelin fiber corresponding to the cylinder-axis of mitral cells. (b) Cylinder-axis of mitral cells. (c) Core fiber from within the glomeruli. (d) Bundles of fibers in the layer of grains. (e) Thin horizontal strands from the higher molecular area. (f) Mitral cells. (g) Glomerulus. (Source: Ramón y Cajal, 1890. Instituto Cajal, Madrid, Spain. See: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Fernando de Castro (1896-1918) drawing illustrating the glomerular layer of the adult dog stained by the Cajal’s gold chloride sublimate method. Legend: (g) Intraglomerular fibrous elements. (a) Radioglomerular corpuscles. (f) Fibrous cells are located superficial to the molecular zone, displaying most of their extensions oriented toward the deepest layers. Note numerous nuclei located in this region, corresponding to Cajal’s adendritic glia. (Source: De Castro, 1920. Instituto Cajal, Madrid, Spain. See: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Fernando de Castro (1896-1918) drawing of human olfactory bulb stained with Cajal’s gold chloride sublimate method. Legend: (A) Superficial substratum of the molecular layer with numerous cephalopodic cells. (B) Deep substratum. (C) Mitral cell layer. (D) Grains layer. (Source: De Castro, 1920. Instituto Cajal, Madrid, Spain. See: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Cajal drawing of an olfactory bulb section from a several-day-old cat. Legend: (A) Glomerular layer. (B) Outer plexiform layer. (C) Mitral cell layer. (D) Inner plexiform layer. (D) Grains layer. (E) White matter. (a) Terminal arborization of an olfactory fiber. (b) Glomerulus with several endings. (c) Mitral plume. (d) Tufted cells. (Source: Ramón y Cajal S. Estudios sobre la corteza cerebral humana. IV. Estructura de la corteza cerebral olfativa del hombre y mamíferos. Trab Lab Invest Biol 1901;1:1-140. Instituto Cajal, Madrid, Spain. See: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Drawing by Cajal’s disciple Tomás Blanes Viale (1878-1900), showing periglomerular cells of a cat glomerular layer. Legend: (A) Cell branching into three glomeruli. (B-D) Biglomerular cells. (C-E) Monoglomerular cells. (a) Axon. (Source: Blanes T. Sobre algunos puntos dudosos de la estructura del bulbo olfatorio. Rev Trimest Microgr 1898;3:99-127. Instituto Cajal, Madrid, Spain. See: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Coronal section of a mouse olfactory bulb stained with hematoxylin and eosin and showing the different layers described by Cajal in previous figure (“Rabbit olfactory bulb, frontal section”). Legend: EPL: External plexiform layer; GcL: Granular and white matter layer; GL: Glomerular layer; IPL: Inner plexiform layer; MCL: Mitral cells layer; ONL: Olfactory nerve layer. (Source: Ramón y Cajal S. Estudios sobre la corteza cerebral humana. IV. Estructura de la corteza cerebral olfativa del hombre y mamíferos. Trab Lab Invest Biol 1901;1:1-140. Instituto Cajal, Madrid, Spain. Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Cajal's drawing of the frontal section of the rabbit olfactory bulb, showing the layered distribution of cells. Legend: (1) Olfactory nerve layer. (2) Glomerular layer. (3) External plexiform layer. (4) Mitral cells layer. (5) Inner plexiform layer. (6) Granular and white matter layer. (a) Peripheral tufted cells, (b) middle; (c) internal (d) short axon cells. (Source: Ramón y Cajal S. Estudios sobre la corteza cerebral humana. IV. Estructura de la corteza cerebral olfativa del hombre y mamíferos. Trab Lab Invest Biol 1901;1:1-140. Instituto Cajal, Madrid, Spain. Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Axonal arborizations of olfactory sensory neuron axons in several glomeruli stained with the Golgi method. (Source: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Cajal's schematic drawing of the mammal’s olfactory system. Legend: (A) Olfactory lobe. (B) Olfactory bulb’s glomerular layer. (C) Cribriform plate. (D) Olfactory epithelium or nasal mucosa. (a) Supporting cells. (b) Olfactory sensory neurons. (Source: Ramón y Cajal S. Nuevo concepto de la Histología de los centros nerviosos. Conferencia III. Rev Cienc Méd Barc 1892;18:457-76. Instituto Cajal, Madrid, Spain. See also: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemistry for the Tuj1 marker in mouse olfactory epithelium shows both mature and immature olfactory sensory neurons. (Source: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Photomicrograph by Albert Blanchart. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Olfactory epithelium labeled E18 cells after in-utero electroporation of an EGP-expressing plasmid injected into the olfactory placode at E14 (green). Hoechst (blue). Sagittal mouse section. a-e, n correspond to the counterpart structures labeled by Cajal in previous figure (“Cell types and their morphologies in the olfactory epithelium”). Legend: Olfactory sensory neurons components: (n) nucleus, (b) dendrite, (c) apical cilia, (a) axon, (d) olfactory sensory neuron axons bundle, (e) supporting or sustentacular cell. (Source: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Cajal drawing illustrating the cell types and their morphologies in the olfactory epithelium. Legend: Olfactory sensory neuron components: (n) nucleus, (b) dendrite, (c) apical cilia, (a) axon, (d) olfactory sensory neuron axons bundle, (e) supporting or sustentacular cell. The drawing shows the handwriting of Cajal with specific instructions for the required reduction publication factor in the margins. (Source: Instituto Cajal, Madrid, Spain. Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Olfactory sensory neurons (green) at E17, labeled after in-utero electroporation of an EGP-expressing plasmid into the olfactory placode at E11. Nuclei counterstained with Hoechst (blue). Sagittal mouse brain section. (Source: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Immunohistochemical staining for Dab1 protein (reelin signaling mediator, green) and Map2a,b protein (microtubule-associated protein, red) on mouse olfactory bulb sections at P3. Nuclei counterstained with Hoechst (blue). Legend: (D) Olfactory nerve layer. (E) Olfactory glomerular layer. (F) External plexiform layer. (G) Mitral cell body layer. (H) Internal plexiform layer. (I) Granule layer. (Source: Martín-López E, Blanchart A, De Carlos JA, López-Mascaraque L. Dab1 (Disable homolog-1) reelin adaptor protein is overexpressed in the olfactory bulb at early postnatal stages. PLoS One 2011;6[10]:e26673. See also: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Cajal’s diagram outlining the circuitry and the trajectory of the nerve impulse (1894). The trajectory of the nerve impulse is shown by arrows. (A) Bipolar cells of the olfactory mucosa. (B) Olfactory glomeruli. (C) Mitral cells. (D) Grains. (E) External root (lateral olfactory tract). (F) Olfactory cortex. (a) Small tufted cell. (b) Main dendrite of a mitral cell. (c) Terminal branch of a grain. (e) Recurrent collaterals of a mitral cell. (g) Surface triangular cells of the olfactory cortex. (h) Epithelial cells of the nasal mucosa. (Source: Ramón y Cajal S. Croonian Lecture: la fine structure des centres nerveux. Proc R Soc Lond 1894;55:444-68. Instituto Cajal, Madrid, Spain. See: Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Cartoon of the olfactory system by Santiago Ramón y Cajal (1894). (Source: Instituto Cajal, Madrid, Spain. Figueres-Oñate M, Gutiérrez Y, López-Mascaraque L. Unraveling Cajal's view of the olfactory system. Front Neuroanat 2014;8:55. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Santiago Ramón y Cajal's drawing of an anteroposterior section of the olfactory bulb of the duck. Legend: (A) arborization of olfactory fibrils within the glomeruli. (B) Descending trunks of the large tufted cells, terminating in a granulous meshwork in the glomeruli. (C) Large superior tufted cells. (Source: Ramón y Cajal S. Origen y terminación de las fibras nerviosas olfatorias [Origin and termination of the olfactory nerve fibers]. Gaceta Sanitaria de Barcelona 1890-1891:3; 133-139, 174-181, 206-212. See: Shepherd GM, Greer CA, Mazzarello P, Sassoè-Pognetto M. The first images of nerve cells: Golgi on the olfactory bulb 1875. Brain Res Rev. 2011;66[1-2]:92-105. Public domain.)

Santiago Ramón y Cajal's drawing of an anteroposterior section of the olfactory bulb and nasal mucosa of a newborn rat. Legend: (A) Olfactory epithelium situated below the cribriform plate; (a) bipolar cell, (b) epithelial or supporting cell. (B) Dermis of the mucosa and bundles of olfactory fibers. (C) Cribriform plate. (D) Olfactory nerve layer. (E) Olfactory glomerular layer. (F) External plexiform layer. (G) Mitral cell body layer. (H) Internal plexiform layer. (I) Granule layer. (c) Cartilage. (e) Olfactory nerves. (f) Arborization of olfactory axons in the glomeruli. (g) Central axon of an inferior tufted cell. (h) Mitral cell. (i) Granules. (j) Epithelial cells. (n) More inferior granule. (m) Terminal filament of epithelial cells. (o) Large stellate cell. (Source: Ramón y Cajal S. Origen y terminación de las fibras nerviosas olfatorias [Origin and termination of the olfactory nerve fibers]. Gaceta Sanitaria de Barcelona 1890-1891:3; 133-139, 174-181, 206-212. See: Shepherd GM, Greer CA, Mazzarello P, Sassoè-Pognetto M. The first images of nerve cells: Golgi on the olfactory bulb 1875. Brain Res Rev. 2011;66[1-2]:92-105. Public domain.)

Semi-schematic drawing of a fragment of a vertical section of the olfactory bulb of a dog: Camillo Golgi's image of a dog’s olfactory bulb, impregnated by the Golgi method. (Source: Golgi C. Sulla Fina Struttura del Bulbi Olfattorii. Reggio-Emilia: Stefano Calderini, 1875. See: Shepherd GM, Greer CA, Mazzarello P, Sassoè-Pognetto M. The first images of nerve cells: Golgi on the olfactory bulb 1875. Brain Res Rev. 2011;66[1-2]:92-105. DeFelipe J. Cajal’s Butterflies of the Soul: Science and Art. New York: Oxford University Press, 2010. DeFelipe J. The dendritic spine story: an intriguing process of discovery. Front Neuroanat. 2015;9:14. Public domain.)

This is a unique representation of the medieval cell doctrine and the special senses because it not only shows the connections of some of the special sense organs to the brain (nose, eyes, and ears but not tongue) but also the sensory stimuli that undergo transduction in the special sensory organs. Also depicted are the olfactory bulbs at the bridge of the nose. (Source: Eck J. Aristotele Stagyritae Philosophi [Libri III: De anima]. Augsburg: Sigismund Grimm & Marcus Wirsung, 1520. Bayerische Staatsbibliothek [Bavarian State Library], Munich. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99.)

Copperplate engraving by Peter Weinher the Elder (1572). (Source: Staatliche Graphische Sammlung, München, via Wikimedia Commons. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

Woodcut of the medieval cell doctrine (1518) by Johann Peyligk (1474-1512) in Leipzig. These are unique among woodcuts of this period in showing both lateral ventricles. This woodcut labels the functions of the special sensory organs but does not show connections between the special sensory organs and the brain. This edition does show a projected representation of the olfactory bulbs at the bridge of the nose. (Source: Herzog August Bibliothek, Wolfenbüttel, Lower Saxony, Germany. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Creative Commons Namensnennung-Weitergabe unter gleichen Bedingungen 3.0 Deutschland [CC BY-SA 3.0 DE] license.)

From the Kingdom of Majorca on the east coast of Spain. Copperplate engraving, sixteenth or seventeenth century. (Source: Dibner Library of the History of Science and Technology, Smithsonian Institution, Washington, D.C. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

Woodcut of the medieval cell doctrine from French author Guillaume Le Lièvre (Gulielmus Leporeus; fl. c. 1520). The olfactory bulbs are depicted as a pair of round structures at the bridge of the nose, and both show projections from these structures to the sensus communis in the anterior portion of the anterior ventricle. The same woodcut was printed in editions in 1520 and 1523. (Source: Österreichische Nationalbibliothek [Austrian National Library], Vienna. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

Lithograph after a painting by British portrait painter James Ramsay (1786-1854), completed between 1830 and 1840 at the Royal College of Physicians (Burgess 1973, 109). (Source: Courtesy of the Wellcome Collection. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Creative Commons 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Dolce L. Le prime imprese del conte Orlando/di M. Lodovico Dolce; da lvi composte in ottava rima et nvovamente stampate; con argomenti et allegorie per ogni canto, et una tauola de’ nomi & delle cose più notabili. [The first exploits of Count Orlando . . .]. Vinegia [Venice]: Gabriel Giolito de Ferrari, 1572. Courtesy of the Getty Research Institute, Los Angeles, California. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

Representation of the medieval cell doctrine (1562) from Venetian humanist writer Lodovico (or Luigi) Dolce (1508/10-1568). This is a close copy of the representation of the medieval cell doctrine by Romberch (1520). Note the engraved connections from the special sense organs to the brain, particularly from the olfactory bulbs to the sensus communis in the anterior portion of the anterior ventricle. (Source: Bayerische Staatsbibliothek [Bavarian State Library], Munich. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

Representation of the medieval cell doctrine (1520) from German Dominican Johannes Romberch (Johann Horst von Romberch; c. 1480-1532/1533). Note the engraved connections from the special sense organs to the brain, particularly from the olfactory bulbs to the sensus communis in the anterior portion of the anterior ventricle. (Source: Biblioteca Nazionale Centrale di Roma [Central National Library of Rome]. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

Representations of the medieval cell doctrine from Polish philosopher and polymath Jan Głogowczyk (c. 1445?-1507), published posthumously in 1514. The 1514 image is derived from Reisch’s (1503) image and shows the Reisch scheme of connections from the special sense organs to the anterior ventricle, including a representation of the olfactory bulbs. (Source: Biblioteka Narodowa [National Library], Warsaw. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

Drawing after an earlier woodcut. From Demby and Piątkowski, 1898. (Source: Biblioteka Narodowa [National Library], Warsaw. See: Lanska DJ. Representations of the olfactory bulb and tracts in images of the medieval cell doctrine. J Hist Neurosci 2022b;31[2-3]:176-99. Public domain.)

CT of the cribriform plate (asterisk). (Source: Romano N, Federici M, Castaldi A. Imaging of cranial nerves: a pictorial overview: insights Imaging. 2019;10[1]:33. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

MRI of the normal olfactory nerves (circles). Steady-state free procession, axial plane. (Source: Romano N, Federici M, Castaldi A. Imaging of cranial nerves: a pictorial overview: insights Imaging. 2019;10[1]:33. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Romano N, Federici M, Castaldi A. Imaging of cranial nerves: a pictorial overview: insights Imaging. 2019;10[1]:33. Creative Commons Attribution 4.0 International [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Ciurleo R, De Salvo S, Bonanno L, Marino S, Bramanti P, Caminiti F. Parosmia and neurological disorders: a neglected association. Front Neurol 2020;11:543275. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging. (Source: Ciurleo R, De Salvo S, Bonanno L, Marino S, Bramanti P, Caminiti F. Parosmia and neurological disorders: a neglected association. Front Neurol 2020;11:543275. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Immunofluorescence of human olfactory epithelium suitable for morphological analysis in biopsy from the superior nasal septum with neuronal marking. (A) Anti-olfactory marker protein antibody (OMP 1:100, for mature olfactory neurons) marking; (B and C) Anti-beta tubulin III label (β3 1:100, total, for mature and immature neurons). The red arrows indicate the presence of nerve bundles. Scale bar 25 μm. (Source: Garcia EC, Luz LA, Anzolin LK, et al. Biopsy of the olfactory epithelium from the superior nasal septum: is it possible to obtain neurons without damaging olfaction? Braz J Otorhinolaryngol 2022;88[5]:787-93. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(A) Detachment of the olfactory mucosa from the right nasal septum (NS) medial to the superior turbinate (ST) and medium turbinate (MT). (B) Cutting instrument removing the epithelium without damaging the tissue. (C) Olfactory epithelium harvested. (Source: Garcia EC, Luz LA, Anzolin LK, et al. Biopsy of the olfactory epithelium from the superior nasal septum: is it possible to obtain neurons without damaging olfaction? Braz J Otorhinolaryngol 2022;88[5]:787-93. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Dr. Mary Broadfoot Walker first demonstrated the effectiveness of physostigmine in the treatment of myasthenia gravis. (Source: Wellcome Institution, London, UK. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

(Source: Wellcome Institution, London, UK. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Oil on canvas by George Reid (1841-1913). He introduced physostigmine into ophthalmic practice, and the Argyll Robertson pupil is named after him. (Source: Wikimedia Commons. Public domain.)

(Source: Wellcome Institution, London, UK. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

At the time of this photograph, Dr. Ogle was Assistant Physician and Lecturer on Pathology at St. George's Hospital. (Source: U.S. National Library of Medicine. Public domain.)

Sir Robert Christison became an authority on poisons, and his treatise on them was published in 1829. In the course of his research he undertook experiments on himself, such as taking large doses of Calabar bean (physostigmine). (Source: Wellcome Institution, London, UK. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

(Photograph by the United Kingdom Government. Public domain.)

Together with Gerhard Peters and Walter Heerdt, Tesch developed a process for manufacturing hydrogen cyanide so it could be used in a solid form as an insecticide: Zyklon B. Tesch was the owner of Tesch & Stabenow (called Testa), a pest control company he co-founded in 1924 with Paul Stabenow in Hamburg, Germany. Tesch became a supporting member of the Nazi party in 1933. During World War II, Tesch & Stabenow sold massive quantities of Zyklon B to the SS. The gas was sold to concentration camps in Auschwitz, Sachsenhausen, Neuengamme, Gross-Rosen, Majdanek, and Ravensbrück. In these camps, the SS used Zyklon B to murder approximately 1.1 million people. Following the end of World War II, Tesch was arrested by the British as a war criminal, tried, and executed. Tesch and his co-executive, Karl Weinbacher, were the only businessmen to be executed for their role in Nazi atrocities in Western Europe. (Photograph by the United Kingdom Government. Public domain.)

Source: Photo by CEphoto, Uwe Aranas, 2017. Used with permission. Photograph edited by Dr. Douglas J Lanska. Cropped and straightened.)

(Source: Organisation for the Prohibition of Chemical Weapons, the implementing body for the Chemical Weapons Convention. Public domain.)

The Battle of Shanghai was the first of the 22 major engagements fought between the National Revolutionary Army of the Republic of China and the Imperial Japanese Army of the Empire of Japan at the beginning of the Second Sino-Japanese War. It was one of the largest and bloodiest battles of the entire war and is often regarded as the battle where World War II started. (Source: Wikimedia Commons. Public domain.)

(Source: U.S. Army Soldier and Biological Chemical Command [SBCCOM]. Public domain.)

The rapid absorption of antidote following automatic injection is enhanced by the degree of tissue dispersion achieved by the autoinjector. The x-ray shows autoinjector doses (on left) compared to standard syringe intramuscular doses (on right). The autoinjector medication is obviously more efficiently diffused into surrounding muscle due to the force with which it is expelled from the injector (as seen in inset photo.) (Source: U.S. Army Soldier and Biological Chemical Command [SBCCOM]. Public domain.)

(Source: U.S. Agency for Toxic Substances and Disease Registry. Case Studies in Environmental Medicine: Cholinesterase Inhibitors: Including Pesticides & Chemical Warfare Nerve Agents, 2007. Public domain. Data source: Sofer S, Tal A, Shahak E. Carbamate and organophosphate poisoning in early childhood. Pediatric Emergency Care 1989;5:222-5.)

(Source: U.S. Agency for Toxic Substances and Disease Registry. Case Studies in Environmental Medicine: Cholinesterase Inhibitors: Including Pesticides & Chemical Warfare Nerve Agents, 2007. Public domain.)

Painting by British portrait painter Héléna Arsène Darmesteter (1854-1923). (Source: Wikimedia Commons. Girton College, University of Cambridge; supplied by The Public Catalogue Foundation. Public domain.)

(Source: U.S. Library of Congress. Public domain. Photograph edited by Dr. Douglas J Lanska.)

(Source: ArbotNet, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

(Source: ArbotNet, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

Technical Emergency Response Training students perform a final exercise in Northville, a fictional town at the Chemical, Ordnance, Biological, and Radiological facility. During the exercise, students work with and identify biological materials Ricin and Anthrax and also nerve agents GB and VX. The exercise was conducted in Anniston, Alabama on March 1, 2014. (Source: Photograph by Benjamin Crossley [2014]. Department of Homeland Security. Federal Emergency Management Agency. Public Affairs Division. Unrestricted. National Archives and Records Administration, College Park, Maryland. Public domain.)

Technical Emergency Response Training students perform a final exercise in Northville, a fictional town at the Chemical, Ordnance, Biological, and Radiological facility. During the exercise, students work with and identify biological materials Ricin and Anthrax and also nerve agents GB and VX. The exercise was conducted in Anniston, Alabama on March 1, 2014. (Source: Photograph by Benjamin Crossley [2014]. Department of Homeland Security. Federal Emergency Management Agency. Public Affairs Division. Unrestricted. National Archives and Records Administration, College Park, Maryland. Public domain.)

Technical Emergency Response Training students perform a final exercise in Northville, a fictional town at the Chemical, Ordnance, Biological, and Radiological facility. During the exercise, students work with and identify biological materials ricin and anthrax and also nerve agents GB and VX. The exercise was conducted in Anniston, Alabama on March 1, 2014. (Source: Photograph by Benjamin Crossley [2014]. Department of Homeland Security. Federal Emergency Management Agency. Public Affairs Division. Unrestricted. National Archives and Records Administration, College Park, Maryland. Public domain.)

A United States Army Survey Team member with the 21st Weapons of Mass Destruction-Civil Support Team (WMD-CST), New Jersey National Guard, is placed on a decontamination line during a training exercise at Fort Hancock and Sandy Hook Proving Ground National Historic Landmark, Sandy Hook, New Jersey, on September 25, 2018. The 21st WMD-CST supports civil authorities at man-made or natural disasters by identifying chemical, biological, radiological, and nuclear substances, as well as assessing the consequences, advising on response measures, and assisting in requesting follow-on forces. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A United States Army Survey Team member with the 21st Weapons of Mass Destruction-Civil Support Team (WMD-CST), New Jersey National Guard, is decontaminated during a training exercise at Fort Hancock and Sandy Hook Proving Ground National Historic Landmark, Sandy Hook, New Jersey, on September 25, 2018. The 21st WMD-CST supports civil authorities at man-made or natural disasters by identifying chemical, biological, radiological, and nuclear substances, as well as assessing the consequences, advising on response measures, and assisting in requesting follow-on forces. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A United States Army Survey Team member with the 21st Weapons of Mass Destruction-Civil Support Team (WMD-CST), New Jersey National Guard, is decontaminated during a training exercise at Fort Hancock and Sandy Hook Proving Ground National Historic Landmark, Sandy Hook, New Jersey, on September 25, 2018. The 21st WMD-CST supports civil authorities at man-made or natural disasters by identifying chemical, biological, radiological, and nuclear substances, as well as assessing the consequences, advising on response measures, and assisting in requesting follow-on forces. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A United States Army Survey Team member with the 21st Weapons of Mass Destruction-Civil Support Team (WMD-CST), New Jersey National Guard, is moved down the decontamination line during a training exercise at Fort Hancock and Sandy Hook Proving Ground National Historic Landmark, Sandy Hook, New Jersey, on September 25, 2018. The 21st WMD-CST supports civil authorities at man-made or natural disasters by identifying chemical, biological, radiological, and nuclear substances, as well as assessing the consequences, advising on response measures, and assisting in requesting follow-on forces. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A Strike Team member with the New Jersey National Guard's 21st Weapons of Mass Destruction-Civil Support Team (WMD-CST), prepares to get scrubbed at a decontamination station by Picatinny Arsenal during a training exercise with the Picatinny Arsenal Fire Department at the New Jersey Homeland Defense Homeland Security Center at Picatinny Arsenal, New Jersey, on March 23, 2017. The 21st WMD-CST is a joint unit comprised of New Jersey National Guard Soldiers and Airmen whose mission is to support civil authorities by identifying chemical, biological, radiological, and nuclear substances in either man-made or natural disasters. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A Strike Team member with the New Jersey National Guard's 21st Weapons of Mass Destruction-Civil Support Team (WMD-CST), is scrubbed at a decontamination station by Picatinny Arsenal during a training exercise with the Picatinny Arsenal Fire Department at the New Jersey Homeland Defense Homeland Security Center at Picatinny Arsenal, New Jersey, on March 23, 2017. The 21st WMD-CST is a joint unit comprised of New Jersey National Guard Soldiers and Airmen whose mission is to support civil authorities by identifying chemical, biological, radiological, and nuclear substances in either man-made or natural disasters. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A Survey Team member, 21st Civil Support Team (Weapons of Mass Destruction), New Jersey National Guard, prepares his sample kit at a county facility in Dias Creek, New Jersey, on November 5, 2008. Soldiers and Airmen of the 21st Civil Support Team were evaluated by the 5th Army (ARNORTH) Civil Support Readiness Group-East. (Source: U.S. Air National Guard photo by Tech. Sgt. Mark Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A Chemical, Biological, Radiological, and Nuclear (CBRN) Marine with CBRN platoon, Headquarters Battalion, 3rd Marine Division lies on a table as fellow Marines remove his gear after passing out in the field within a contaminated environment as a simulated casualty during a CBRN training exercise at landing zone Westfield on May 13, 2014. Marines conducted assessment and consequence management training through several scenarios to sustain familiarity with safely conducting research and gathering samples in a contaminated environment. One scenario contained an aircraft leaking chemical agents while the other scenario included locating a chemical agent spill and rescuing multiple casualties in the field. Both scenarios utilized the Rapid Area Sensitive Sight and Reconnaissance robot to investigate the hazardous areas to search for and mitigate potentially harmful substances CBRN personnel may not be aware of. (Source: U.S. Marine Corps photo by Lance Cpl. Matthew Bragg/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

Chemical, Biological, Radiological, and Nuclear (CBRN) Marines with CBRN platoon, Headquarters Battalion, 3rd Marine Division, clear the area after gathering samples during an aircraft chemical leak training scenario at Westfield on May 13, 2014. Marines conducted assessment and consequence management training through several scenarios to sustain familiarity with safely conducting research and gathering samples in a contaminated environment. One scenario contained an aircraft leaking chemical agents, and the other scenario included locating a chemical agent spill and rescuing multiple casualties in the field. Both scenarios utilized the Rapid Area Sensitive Sight and Reconnaissance robot to investigate the hazardous areas to search for and mitigate potentially harmful substances CBRN personnel may not be aware of. (Source: U.S. Marine Corps photo by Lance Cpl. Matthew Bragg/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

Chemical, Biological, Radiological, and Nuclear Marines with the 24th Marine Expeditionary Unit search for casualties in a metro line during a course at the Guardian Centers of Georgia in Perry, Ga. October 30, 2020. The course allows Marines to expand their knowledge of procedures and equipment through training in realistic environments. (Source: U.S. Marines Corps photo by Lance Cpl. Nicholas Guevara/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

Chemical, Biological, Radiological, and Nuclear Marines with the 24th Marine Expeditionary Unit evacuate a casualty in a realistic metro line during a course at the Guardian Centers of Georgia in Perry, Georgia, on October 30, 2020. The course allows Marines to expand their knowledge of procedures and equipment through training in realistic environments. (Source: U.S. Marines Corps photo by Lance Cpl. Nicholas Guevara/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

Chemical, Biological, Radiological, and Nuclear Marines with the 24th Marine Expeditionary Unit scan a wash rag for contamination during a course at the Guardian Centers of Georgia in Perry, Georgia, on October 22, 2020. The course allows Marines to expand their knowledge of procedures and equipment through training in realistic environments. (Source: U.S. Marines Corps photo by Lance Cpl. Nicholas Guevara/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

Chemical, Biological, Radiological, and Nuclear Marines with the 24th Marine Expeditionary Unit evacuate a casualty in a realistic metro line during a course at the Guardian Centers of Georgia in Perry, Georgia, on October 30, 2020. The course allows Marines to expand their knowledge of procedures and equipment through training in realistic environments. (Source: U.S. Marines Corps photo by Lance Cpl. Nicholas Guevara/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

Chemical, Biological, Radiological, and Nuclear Marines with the 24th Marine Expeditionary Unit conduct decontamination procedures on an anatomical donation during a course at the Guardian Centers of Georgia in Perry, Georgia, on October 25, 2020. The course allows Marines to expand their knowledge of procedures and equipment through training in realistic environments. (Source: U.S. Marines Corps photo by Lance Cpl. Nicholas Guevara/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A Picatinny Arsenal firefighter, left, checks a New Jersey National Guard 21st Weapons of Mass Destruction-Civil Support Team Strike Team member for contamination during a training exercise with the Picatinny Arsenal Fire Department at the New Jersey Homeland Defense Homeland Security Center at Picatinny Arsenal, New Jersey, on March 23, 2017. The 21st WMD-CST is a joint unit comprised of New Jersey National Guard Soldiers and Airmen whose mission is to support civil authorities by identifying chemical, biological, radiological, and nuclear substances in either man-made or natural disasters. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

A Picatinny Arsenal firefighter, left, checks a New Jersey National Guard 21st Weapons of Mass Destruction-Civil Support Team Strike Team member for contamination during a training exercise with the Picatinny Arsenal Fire Department at the New Jersey Homeland Defense Homeland Security Center at Picatinny Arsenal, New Jersey, on March 23, 2017. The 21st WMD-CST is a joint unit comprised of New Jersey National Guard Soldiers and Airmen whose mission is to support civil authorities by identifying chemical, biological, radiological, and nuclear substances in either man-made or natural disasters. (Source: New Jersey National Guard photo by Mark C. Olsen/Released. National Archives and Records Administration and the Defense Visual Information Distribution Service. Public Domain Dedication.)

(Source: ArbotNet, Centers for Disease Control and Prevention, Atlanta, Georgia. Public domain.)

(Source: U.S. National Archives [1984]. Combined Military Service Digital Photographic Files. Released to the public. Public domain.)

The salsa bar of The Dalles' Taco Time that had been intentionally contaminated as part of the Rajneeshee cult bioterrorism attack in 1983 in The Dalles, Oregon. (Source: Wikimedia Commons. User: Cacophony [2008]. Creative Commons Attribution 3.0 Unported [CC BY 3.0] license, creativecommons.org/licenses/by/3.0/deed.en.)

Four of the restaurants in The Dalles, Oregon, affected by the Rajneeshee cult bioterrorism incident in 1984. (Source: Wikimedia Commons. User: Cacophony [2008]. Creative Commons Attribution 3.0 Unported [CC BY 3.0] license, creativecommons.org/licenses/by/3.0/deed.en.)

(Source: Wikimedia Commons. Image by Sjakkelien Vollebregt [1984]. Nationaal Archief, the Dutch National Archives. Creative Commons CC0 1.0 Universal Public Domain Dedication.)

(Source: Wikimedia Commons. Image by Sjakkelien Vollebregt [1984]. Nationaal Archief, the Dutch National Archives. Creative Commons CC0 1.0 Universal Public Domain Dedication.)

(Source: Wikimedia Commons. Image by Redheylin [1977]. Creative Commons CC0 1.0 Universal Public Domain Dedication.)

Rajneeshee cult members in the summer of 1982, 2 years before cult members perpetrated the largest bioterrorism event in United States history. (Source: © 2003 Samvado Gunnar Kossatz. Available at: web.archive.org/web/20071026130939/http://m31.de/ranch/index.html. Used with permission.)

Rajneeshee cult members in the summer of 1982, 2 years before cult members perpetrated the largest bioterrorism event in United States history. (Source: © 2003 Samvado Gunnar Kossatz. Available at: web.archive.org/web/20071026130939/http://m31.de/ranch/index.html. Used with permission.)

Rajneeshee cult members in the summer of 1982, 2 years before cult members perpetrated the largest bioterrorism event in United States history. (Source: © 2003 Samvado Gunnar Kossatz. Available at: web.archive.org/web/20071026130939/http://m31.de/ranch/index.html. Used with permission.)

The compound of the Rajneeshee cult in The Dalles, Oregon, 1982. (Source: © 2003 Samvado Gunnar Kossatz. Available at: web.archive.org/web/20071026130939/http://m31.de/ranch/index.html. Used with permission.)

Members of the Rajneeshee cult watch their leader, Osho Rajneesh drive by in a car in the summer of 1982, 2 years before cult members perpetrated the largest bioterrorism event in United States history. (Source: © 2003 Samvado Gunnar Kossatz. Available at: web.archive.org/web/20071026130939/http://m31.de/ranch/index.html. Used with permission.)

Histopathologic features from a 5-year-old girl with eastern equine encephalitis in 2005, as part of a study of eastern equine encephalitis in Massachusetts and New Hampshire from 1970 to 2010. The postmortem samples of central nervous system tissue were obtained 10 days after the onset of symptoms. Eastern equine encephalitis virus colocalizes with areas of tissue injury in the brain. Immunohistochemistry with eastern equine encephalitis immune ascites demonstrates eastern equine encephalitis viral antigens in the thalamus. Specificity for Eastern equine encephalitis virus immunoreactivity of this ascites fluid was confirmed by the lack of staining on control brain specimens. (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Histopathologic features from a 5-year-old girl with eastern equine encephalitis in 2005, as part of a study of eastern equine encephalitis in Massachusetts and New Hampshire from 1970 to 2010. The postmortem samples of central nervous system tissue were obtained 10 days after the onset of symptoms. Eastern equine encephalitis virus colocalizes with areas of tissue injury in the brain. H&E stained section of thalamus (magnification ×100). (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Histopathologic features from a 5-year-old girl with eastern equine encephalitis in 2005, as part of a study of eastern equine encephalitis in Massachusetts and New Hampshire from 1970 to 2010. The postmortem samples of central nervous system tissue were obtained 10 days after the onset of symptoms. Eastern equine encephalitis virus colocalizes with areas of tissue injury in the brain. Immunohistochemistry of section adjacent to that shown in the previous figure; staining of the basal ganglia with eastern equine encephalitis immune ascites demonstrates foci of eastern equine encephalitis virus (arrow) that correspond with areas of tissue rarefaction in the previous figure (magnification ×12.5). (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Histopathologic features from a 5-year-old girl with eastern equine encephalitis in 2005, as part of a study of eastern equine encephalitis in Massachusetts and New Hampshire from 1970 to 2010. The postmortem samples of central nervous system tissue were obtained 10 days after the onset of symptoms. Eastern equine encephalitis virus colocalizes with areas of tissue injury in the brain. H&E-stained section of the basal ganglia, demonstrating foci of marked tissue rarefaction (arrow) (magnification ×12.5). (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Histopathologic features from a 5-year-old girl with eastern equine encephalitis in 2005, as part of a study of eastern equine encephalitis in Massachusetts and New Hampshire from 1970 to 2010. The postmortem samples of central nervous system tissue were obtained 10 days after the onset of symptoms. H&E-stained section of midbrain, showing perivascular inflammation (arrow) (magnification ×400). (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Histopathologic features from a 5-year-old girl with eastern equine encephalitis in 2005, as part of a study of eastern equine encephalitis in Massachusetts and New Hampshire from 1970 to 2010. The postmortem samples of central nervous system tissue were obtained 10 days after the onset of symptoms. H&E-stained section of temporal lobe, showing meningeal inflammation (arrow) (magnification ×200). (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Axial FLAIR from a brain MRI scan of a 3.5-year-old girl with eastern equine encephalitis on hospital day 3. The abnormal T2 hyperintense regions are most prominent in the right parietotemporal gray matter (arrow) and subcortical white matter but are also seen scattered throughout. (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Axial FLAIR from a brain MRI scan of a 3.5-year-old girl with eastern equine encephalitis on hospital day 3 showing abnormal T2 hyperintense caudate and thalamic nuclei, most prominent on the right (arrow). (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Axial FLAIR image from a brain MRI scan of a 13-year-old boy with eastern equine encephalitis on hospital day 2 showing abnormal T2 hyperintense regions of the bimesial temporal regions (thick arrows) with accompanying abnormal T2 hyperintense regions of the dorsal pontomesencephalic regions (thin arrows). (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

Noncontrast CT scan of the brain of a 5-year-old girl with eastern equine encephalitis on hospital day 2 showing subtle hypoattenuation of the left caudate head (arrow) and diencephalic region. (Source: Silverman MA, Misasi J, Smole S, et al. Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970-2010. Emerg Infect Dis 2013;19[2]:194-201. Public domain.)

The patient also had abnormally low scores in speech audiometry (not shown). (Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Wide-field fluorescein angiogram demonstrating right eye peripheral (superior, temporal, and inferior) branch artery occlusions and focal arterial leakage in an inferior branch artery. (Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wilf-Yarkoni A, Elkayam O, Aizenstein O, et al. Increased incidence of Susac syndrome: a case series study. BMC Neurol 2020;20[1]:332. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Fundoscopic examination revealed fluffy white patches along the inferotemporal arcade in a 22-year-old man diagnosed with Susac syndrome. Fluorescein angiography confirmed 14 branch artery occlusions and arterial wall hyperfluorescence with leakage of dye (not shown). (Source: Gertner E, Rosenbloom MH. Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report. J Med Case Rep 2016;10[1]:137. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial brain DWI in a 22-year-old man diagnosed with Susac syndrome, showing multifocal subacute punctate supratentorial white matter lesions (black arrows) with the most prominent lesion affecting the posterior corpus callosum (red arrowhead). The study also showed T2/FLAIR hyperintensities involving the deep gray nuclei as well as leptomeningeal enhancement (not shown). (Source: Gertner E, Rosenbloom MH. Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report. J Med Case Rep 2016;10[1]:137. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Livedo reticularis-like skin manifestation occurring on both arms, but nowhere else, one week before presentation and resolving with treatment, in a 22-year-old man diagnosed with Susac syndrome. (Source: Gertner E, Rosenbloom MH. Susac syndrome with prominent dermatological findings and a prompt response to intravenous immunoglobulin, steroids, and rituximab: a case report. J Med Case Rep 2016;10[1]:137. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Large ischemic area in the lower half of the left retina (arrow) and smaller infarct in the top left quadrant (tailed arrow), representing branch retinal artery occlusions in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Axial contrast-enhanced T1-weighted MRI showing multiple small contrast-enhancing lesions (arrows) in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Near-median sagittal T2 MRI demonstrating atrophy of the corpus callosum in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Sagittal T2 MRI showing centrally located corpus callosum lesions (arrow) and one lesion with spoke-like morphology (tailed arrow) in a 32-year-old woman with Susac syndrome. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Diffusion-weighted image from a 32-year-old woman with Susac syndrome; the image shows multiple small lesions exhibiting diffusion restriction (arrows) and correspondingly decreased ADC values (not shown). (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Axial FLAIR image from a 32-year-old woman with Susac syndrome, showing multiple small white matter lesions. (Source: Engeholm M, Leo-Kottler B, Rempp H, et al. Encephalopathic Susac's syndrome associated with livedo racemosa in a young woman before the completion of family planning. BMC Neurol 2013;13:185. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the deep layer, left eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the superficial layer, left eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the deep layer, right eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Foveal avascular zone enlargement in optical coherence tomography angiography images of the superficial layer, right eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Color fundus photography revealing a glass plaque (white arrow) as yellowish lipid sediments at the mid-segment of the retinal arterioles in the left eye. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

(Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Sagittal MRI of a 33-year-old man with Susac syndrome. The red arrow shows an ellipsoid focal lesion involving the corpus callosum. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Transverse MRI of a 33-year-old man with Susac syndrome. The red arrows show various round and ellipsoid focal lesions involving the cerebellum. (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

Transverse MRI of a 33-year-old man with Susac syndrome. The red arrows show various round and ellipsoid focal lesions involving the corpus callosum, periventricular and subcortical white matter, and deep grey matter (basal ganglia and thalami). (Source: Bagaglia SA, Passani F, Oliverio GW, et al. Multimodal imaging in Susac syndrome: a case report and literature review. Int J Environ Res Public Health 2021;18[7]:3435. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/ 4.0.)

On follow-up 18 months after the initial FLAIR sequence, there was generalized brain atrophy with stable white matter lesions. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

On follow-up 2 weeks after the initial brain MRI, FLAIR sequence showed an area of increased T2 signal without diffusion restriction over the left side of the pontine tegmentum. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

On follow-up 2 weeks after the initial brain MRI, diffusion-weighted images showed a new area of diffusion restriction in the left corona radiata, corpus callosum, and right middle cerebral peduncle. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Initial brain MRI in a 56-year-old man with Susac syndrome. Transverse FLAIR images showed increased T2 signal in the areas corresponding to areas of restricted diffusion on diffusion-weighted images. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Initial brain MRI in a 56-year-old man with Susac syndrome. Diffusion-weighted images showed areas of restricted diffusion over the central/left aspect of the splenium of the corpus callosum, left parietal white matter, left basal ganglia, and anterior right cingulate gyrus. (Source: Alshaqi O, Moodie T, Alchaki A. Involuntary crying episodes with Susac's syndrome-a rare presentation of a rare disease: a case report. BMC Neurol 2022;22[1]:155. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal FLAIR sequence on brain MRI from the patient’s last follow-up, showing improvement of the radiological findings. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Transverse FLAIR sequence on brain MRI from the patient’s last follow-up, showing improvement of the radiological findings. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal FLAIR sequence on brain MRI showing hyperintense white matter lesions with "snowball"-like lesions in the corpus callosum. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Transverse FLAIR sequence on brain MRI showing hyperintense white matter lesions with "snowball"-like lesions in the corpus callosum. (Source: Barbero P, Vecchio D, Virgilio E, Naldi P, Comi C, Cantello R. Susac syndrome: an uncommon cause of impaired vision. Neurol Sci 2022;43[6]:3919-22. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T1 MRI showing the pathognomonic central callosal "holes" (microinfarcts) of Susac syndrome. These residual "holes" (and sometimes, "spokes") develop as the acute callosal changes resolve. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Legend: C, cyclophosphamide; IVIg, intravenous immunoglobulin; MM, mycophenolate mofetil. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Audiogram showing bilateral low-frequency sensorineural hearing loss, rising to normal at higher frequencies. This is the typical cochlear hearing loss pattern seen in Susac syndrome, likely reflecting microinfarction of the striae vascularis at the apex of the cochlea. Legend: X = left ear; O = right ear. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Axial T2 image showing multiple white matter lesions, especially in the corpus callosum. The arrows point to 2 of several callosal lesions. (Source: Rennebohm RM, Lubow M, Rusin J, Martin L, Grzybowski DM, Susac JO. Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model. Pediatr Rheumatol Online J 2008;6:3. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

These scores are derived by adding disease activity (0-100) for each domain (brain, ears, eyes). (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Admission MRI revealed multifocal T1 hypointensity and T2 hyperintensity lesions in the periventricular and supraventricular cerebral and cerebellar white matter, including extensive involvement of the corpus callosum. (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

These scores are derived by adding disease activity (0-100) for each domain (brain, ears, eyes). (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI on admission showing several “snowball” lesions in the corpus callosum. (Source: Bullock DR, Spencer RT, Vehe RK, Srivastava S, Rennebohm RM. Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports. J Med Case Rep 2023;17[1]:158. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

This midsagittal view of the brain MRI of a patient with spinocerebellar ataxia type 1 reveals atrophy of the cerebellum and pons, referred to as olivopontocerebellar atrophy. (Contributed by Dr. Pichet Termsarasab.)

Emanuel Favre, a 13-year-old boy had been accidentally struck in the head with an axe while "helping his master to chop wood ... by laying the branches on the block, he had bent too far forwards and the axe of the master struck him on the head" (Mosso 1898). (Source: Patrizi ML. L'Oratori: Saggio sperimentale. Milani [Milan]: Fratelli Treves, 1912:50. Public domain.)

Pulmonary edema aggravates hypoxia due to enlarged alveolar-capillary diffusion distance. Legend: down arrow, leads to; circled minus sign, reduces; circled plus sign, increases. (Source: Tannheimer M, Lechner R. Initial treatment of high-altitude pulmonary edema: comparison of oxygen and auto-PEEP. Int J Environ Res Public Health 2022;19[23]:16185. West JB, Mathieu-Costello O. High altitude pulmonary edema is caused by stress failure of pulmonary capillaries. Int J Sports Med 1992;13 Suppl 1:S54-8. Considering: Luks A, Ainslie PN, Lawley JS, Roach RC, Simonson TS, editors. Ward, Milledge & West’s High Altitude Medicine and Physiology. 6th ed. Boca Raton, Florida: CRC Press, 2021. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The black lines indicate the beginning and end of Auto-PEEP breathing. (Source: Tannheimer M, Lechner R. Initial treatment of high-altitude pulmonary edema: comparison of oxygen and auto-PEEP. Int J Environ Res Public Health 2022;19[23]:16185. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The black line indicates the start of supplemental oxygen at an initial flow rate of 3.0 L/min which was reduced to 0.5-1.0 L/min after several minutes. The grey dotted lines show the attempt of pursed lips breathing that had to be stopped after 12 minutes because of exhaustion. Drugs: administration of dexamethasone 8 mg, nifedipine 20 mg, and ibuprofen 800 mg. After 40 minutes, the patient walked to the helicopter (increasing pulse) using supplemental oxygen. (Source: Tannheimer M, Lechner R. Initial treatment of high-altitude pulmonary edema: comparison of oxygen and auto-PEEP. Int J Environ Res Public Health 2022;19[23]:16185. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Nocturnal SpO₂ levels are calculated from nocturnal pulse oximetry recordings and represent percentage of recording time spent at a given SpO₂ value. Distribution of SpO₂ during the night differed significantly among the three groups. Abbreviations: le, level; Perc.: percentage; SpO₂: oxygen saturation. (Source: Perger E, Baillieul S, Esteve F, et al. Nocturnal hypoxemia, blood pressure, vascular status and chronic mountain sickness in the highest city in the world. Ann Med 2022;54[1]:1884-93. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Nocturnal SpO₂ levels are calculated from nocturnal pulse oximetry recordings and represent the percentage of recording time spent at a specific SpO₂ value. The percentage of total recording time with a SpO2 <65% was significantly different between the no CMS and moderate-severe CMS groups. Abbreviations: le, level; Perc., percentage; SpO₂, oxygen saturation; CMS, chronic mountain sickness. (Source: Perger E, Baillieul S, Esteve F, et al. Nocturnal hypoxemia, blood pressure, vascular status, and chronic mountain sickness in the highest city in the world. Ann Med 2022;54[1]:1884-93. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Carpenter TM. A Comparison of methods for determining the respiratory exchange of man. Washington, DC: The Carnegie Institution of Washington, 1915:56. Public domain.)

(Source: Pagel J. Biographisches Lexikon hervorragender Ärzte des neunzehnten Jahrhunderts: Mit einer historischen einleitung. Berlin: Urban & Schwarzenberg, 1901. Public domain.)

Back row from left to right: British respiratory physiologist Claude Gordon Douglas FRS (1882-1963), German biochemist Carl Neuberg (1877-1956), French astronomer and mathematician Jean Mascart (1872-1935; at Tenerife to observe Halley's Comet), German physician and pulmonologist Gotthold Pannwitz (1861-1926), Austrian physiologist Arnold Durig (1872-1961), "Piasse," and Austrian physiologist and physician Hermann von Schrötter (1870-1928). Middle row from left to right: German pathologist Johannes Orth (1847-1923), Mrs. Neuberg, Commadant (Commander) Bachmann, British physiologist Sir Joseph Barcroft FRS (1872–1947), German physiologist Nathan Zuntz (1847-1920). Front row from left to right: German physician Gotthold Pannwitz (1861-1926), "Carrière." (Source: Mascart J. Impressions et observations dans un voyage à Tenerife, Paris: Flammarion, 1912. Public domain.)

(Source: Hildebrandt A. Die Luftschiffahrt nach ihrer geschichtlichen und gegenwärtigen Entwicklung. München and Berlin: R. Oldenbourg, 1907. Public domain.)

(Source: Emden R. Illustrierte aeronautische Mitteilungen. Deutsche Zeitschrift für Luftschiffahrt. Fachzeitschrift für alle Interessen der Flugtechnik mit ihren Hülfswissenschaften, für aeronautische Industrie und Unternehmungen. Strassburg: Karl J. Trübner, 1901. Public domain.)

(Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

(Source: Mosso A. Life of man on the high Alps. Kiesow EL, trans. London: T Fisher Unwin, 1898:191. Public domain.)

(Source: Mosso A. Life of man on the high Alps. Kiesow EL, trans. London: T Fisher Unwin, 1898:53. Public domain.)

The circle beneath the lever represents theoretically the section of the thorax. (Source: Mosso A. Life of man on the high Alps. Kiesow EL, trans. London: T Fisher Unwin, 1898:32. Public domain.)

(Source: Mosso A. Life of man on the high Alps. Kiesow EL, trans. London: T Fisher Unwin, 1898:248. Public domain.)

C (Top): Cerebral pulse immediately after the subject stopped breathing the artificial air. D (Bottom): Curve registered 2 minutes later. (Source: Mosso A. Life of man on the high Alps. Kiesow EL, trans. London: T Fisher Unwin, 1898:250. Public domain.)

Emanuel Favre, a 13-year-old boy had been accidentally struck in the head with an axe while "helping his master to chop wood ... by laying the branches on the block, he had bent too far forwards and the axe of the master struck him on the head." A (Top): Normal curve. B (Bottom): Curve registered during the respiration of artificial air when the subject was seized with dizziness. (Source: Mosso A. Life of man on the high Alps. Kiesow EL, trans. London: T Fisher Unwin, 1898:249. Public domain.)

Cesare Lasagno, a 14-year-old blacksmith's apprentice, had sustained a wound to the middle of his forehead and a skull fracture after falling from the second story while leaning on his stomach over the bannisters, and "sliding down as boys do." A (Top): Normal curve. B (Middle): Curve of cerebral pulse taken when the rarefaction of the air corresponded to an altitude of 5,111 meters. C (Bottom): Subsequent normal curve. (Source: Mosso A. Life of man on the high Alps. Kiesow EL, trans. London: T Fisher Unwin, 1898:243. Public domain.)

(Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

(Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

(Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

German physiologist Adolf Loewy (1862-1936) shown combining measurement of respiration with the Zuntz portable gas meter with simultaneous registration of pulse and respiratory movements using a kymograph. (Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

Loewy, ready to begin marching with the Zuntz portable gas exchange measuring device. (Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen: Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

A gas exchange measuring device. (Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

The recording and sampling apparatus is shown on the left and the air analysis apparatus at the right. (Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

(Source: Zuntz N, Loewy A, Müller F, Caspari W. Höhenklima und Bergwanderungen in ihrer Wirkung auf den Menschen : Ergebnisse experimenteller Forschungen im Hochgebirge und Laboratorium. Berlin: Bong & Co., 1906. Public domain.)

(Krankenhaus der jüdischen Gemeinde zu Berlin.)

(Source: Mascart J. Impressions et observations dans un voyage à Tenerife. Paris: Ernest Flammarion, 1912. Public domain.)

(Source: Mascart J. Impressions et observations dans un voyage à Tenerife, Paris: Flammarion, 1912. Wellcome Collection. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image edited by Dr. Douglas J Lanska.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

Note that each individual has their own portion of the y-axis (on either the right or left side). The increase was about 1.5 liters and the peak corresponded to passing through tropical climes, when their vascular beds expanded (ie, from cutaneous vasodilation). The individual graphs have simply been staggered vertically. (Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(1000s per ml. of blood) (Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

Increase in red blood corpuscles (millions per ml. of blood) while several expedition members were at high altitude (center peaks). The vertical lines represent the dates on which the party left and returned to Lima, Peru (505 feet or 154 meters above sea level). (Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

(Source: Barcroft J, Binger CA, Bock AV, et al. Observations upon the effect of high altitude on the physiological processes of the human body, carried out in the Peruvian Andes, chiefly at Cerro de Pasco. Philos Trans R Soc Lond B 1923;211:351-480. Public domain.)

¶ Nonfatal emergency department-treated injuries in this height category did not meet criteria for publication without compromise of confidentiality.
§ 95% confidence interval.
Abbreviations: CFOI = Census of Fatal Occupational Injuries; NEISS-Work = National Electronic Injury Surveillance System–occupational supplement; BLS = Bureau of Labor Statistics. Notes: (1) Percentage of ladder fall fatalities was generated with restricted access to BLS CFOI microdata and might differ from results released by BLS.

Fatality counts on which the percentages are calculated are based are 82 cases where ladder height was indicated and include deaths of workers of all ages, volunteer workers, and resident military personnel. (2) Excludes 31 fatalities and 22,600 nonfatal injuries with unknown fall height. (Source: Socias CM, Chaumont Menéndez CK, Collins JW, Simeonov P; Centers for Disease Control and Prevention [CDC]. Occupational ladder fall injuries, United States, 2011. MMWR Morb Mortal Wkly Rep 2014;63(16):341-6. Erratum in: MMWR Morb Mortal Wkly Rep 2014;63(18):416. Public domain.)

(1) Age-adjusted to the 2000 U.S. standard population. (2) Forty-nine states; Alaska and the District of Columbia not shown because total case count was fewer than 20. (Source: Peterson AB, Kegler SR. Deaths from fall-related traumatic brain injury, United States, 2008-2017. MMWR Morb Mortal Wkly Rep 2020;69[9]:225-30. Public domain.)

(Source: Mielenz TJ, Kannoth S, Jia H, et al. Evaluating a two-level vs. three-level fall risk screening algorithm for predicting falls among older adults. Front Public Health 2020;8:373. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Legend: Black, experienced at least a single fall; White, experienced a fall-related injury; W/C, wheelchair; ADLs, activities of daily living. (Source: Chihuri S, Wong CK. Factors associated with the likelihood of fall-related injury among people with lower limb loss. Inj Epidemiol 2018;5[1]:42. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Notes: (1) Rates shown are the number of deaths per 100,000 population. Age-adjusted death rates were calculated by applying age-specific death rates to the 2000 United States standard population age distribution. (2) Deaths from falls were identified using the International Classification of Diseases, Tenth Revision (ICD–10) underlying cause-of-death codes W00–W19. (3) Joinpoint regression examining changes in trends indicated that, from 2007 to 2016, the District of Columbia and 30 states had significant increases in the rate of deaths from falling (Arkansas, California, Connecticut, Florida, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Montana, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, Rhode Island, South Carolina, South Dakota, Virginia, Washington, West Virginia, and Wyoming). Colorado, Oregon, and Tennessee had initial increases, followed by stable rates during this period. Arizona, Nevada, and Wisconsin had an initial period of stability followed by a significant increase. In Missouri, there was a decrease from 2007 to 2012, followed by an increase from 2012 to 2016. In Utah, there was an increase from 2007 to 2012 followed by a decrease to 2016. Eleven states had nonsignificant trends during this period (Alabama, Delaware, Georgia, Hawaii, Mississippi, Nebraska, New Hampshire, New Mexico, North Dakota, Texas, and Vermont). Alaska did not have enough data to examine trends. (Source: Burns E, Kakara R. Deaths from Falls Among Persons Aged ≥65 Years - United States, 2007-2016. MMWR Morb Mortal Wkly Rep. 2018;67[18]:509-514. Public domain. Public domain. Data from National Vital Statistics System, Mortality. CDC WONDER. Available at: wonder.cdc.gov.)

Age-adjusted death rates were calculated by applying age-specific death rates to the 2000 United States standard population age distribution. (Source: Burns E, Kakara R. Deaths from Falls Among Persons Aged ≥65 Years - United States, 2007-2016. MMWR Morb Mortal Wkly Rep. 2018;67[18]:509-514. Public domain.)

Estimates are based on household interviews of a sample of the civilian noninstitutionalized population. (Source: Schiller JS, Kramarow EA, Dey AN. Fall injury episodes among noninstitutionalized older adults: United States, 2001-2003. Advance Data from Vital and Health Statistics 2007;392:1-16. Data from the National Health Interview Surveys, 2001-2003. Public domain.)

(1) Significantly different from those in the normal strength category, p < 0.05. (2) Significantly different from those in the intermediate strength category, p < 0.05. (3) p < 0.05 for linear trend. (Source: Looker AC, Wang CY. Prevalence of reduced muscle strength in older U.S. adults: United States, 2011-2012. NCHS Data Brief. 2015;[179]:1-8. Data from the U.S. National Health and Nutrition Examination Survey, 2011-2012. National Center for Health Statistics. Public domain.)

(1) Significantly different from non-Hispanic Asian persons in the same muscle strength category, p < 0.05. (2) Significantly different from Hispanic persons in the same muscle strength category, p < 0.05. (Source: Looker AC, Wang CY. Prevalence of reduced muscle strength in older U.S. adults: United States, 2011-2012. NCHS Data Brief. 2015;[179]:1-8. Data from the U.S. National Health and Nutrition Examination Survey, 2011-2012. National Center for Health Statistics. Public domain.)

(1) Age-adjusted. (2) Significantly different from men in the same muscle strength category, p < 0.05. (Source: Looker AC, Wang CY. Prevalence of reduced muscle strength in older U.S. adults: United States, 2011-2012. NCHS Data Brief. 2015;[179]:1-8. Data from the U.S. National Health and Nutrition Examination Survey, 2011-2012. National Center for Health Statistics. Public domain.)

(1) Significantly different from those aged 60 to 79 years in the same muscle strength category, p < 0.05. (Source: Looker AC, Wang CY. Prevalence of reduced muscle strength in older U.S. adults: United States, 2011-2012. NCHS Data Brief. 2015;[179]:1-8. Data from the U.S. National Health and Nutrition Examination Survey, 2011-2012. National Center for Health Statistics. Public domain.)

(1) Significantly different from the group below the poverty level. (Source: Dillon CF, Gu Q, Hoffman HJ, Ko CW. Vision, hearing, balance, and sensory impairment in Americans aged 70 years and over: United States, 1999-2006. NCHS Data Brief 2010;31:1-8. Data from the US National Health and Nutrition Examination Survey, National Center for Health Statistics. Public domain.)

(1) Significantly different from non-Hispanic black and Mexican-American persons. (2) Significantly different from non-Hispanic white and Mexican-American persons. (3) Significantly different from non-Hispanic black and non-Hispanic white persons. (4) Significantly different from non-Hispanic white. (Source: Dillon CF, Gu Q, Hoffman HJ, Ko CW. Vision, hearing, balance, and sensory impairment in Americans aged 70 years and over: United States, 1999-2006. NCHS Data Brief 2010;31:1-8. Data from the US National Health and Nutrition Examination Survey, National Center for Health Statistics. Public domain.)

(1) Significantly different from the 70- to 79-year age group. (Source: Dillon CF, Gu Q, Hoffman HJ, Ko CW. Vision, hearing, balance, and sensory impairment in Americans aged 70 years and over: United States, 1999-2006. NCHS Data Brief 2010;31:1-8. Data from the US National Health and Nutrition Examination Survey, National Center for Health Statistics. Public domain.)

(1) Significantly different from men. (Source: Dillon CF, Gu Q, Hoffman HJ, Ko CW. Vision, hearing, balance, and sensory impairment in Americans aged 70 years and over: United States, 1999-2006. NCHS Data Brief 2010;31:1-8. Data from the US National Health and Nutrition Examination Survey, National Center for Health Statistics. Public domain.)

(Source: Dillon CF, Gu Q, Hoffman HJ, Ko CW. Vision, hearing, balance, and sensory impairment in Americans aged 70 years and over: United States, 1999-2006. NCHS Data Brief 2010;31:1-8. Data from the US National Health and Nutrition Examination Survey, National Center for Health Statistics. Public domain.)

(Source: Centers for Disease Control and Prevention. Cost of older adult falls. Available at www.cdc.gov/falls/data/fall-cost.html. Public domain.)

(Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

(Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

(Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

(Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

Legend: Am Indian/AK Native, American Indian/Alaska native; Asian/PI, Asian/Pacific Islander. (Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

Legend: Green, non-Hispanic white; light blue, Hispanic white; purple, non-Hispanic black; olive, Hispanic black. (Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

Legend: Purple, 85+; light blue, 80 to 85; teal, 75 to 79; pink, 70-74; grey, 65 to 69. Other age groups are not distinguishable in this graph. (Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

Legend: Blue, all; Green, suicide; Purple, unintentional. (Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

Legend: Blue, all; Green, suicide; Purple, unintentional. (Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

Legend: Blue, all; Green, suicide; Purple, unintentional. (Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

(Legend: Blue, all; Green, suicide; Purple, unintentional. (Source: Web-based Injury Statistics Query and Reporting System [WISQARS]. Centers for Disease Control and Prevention. Public domain.)

(Source: Centers for Disease Control and Prevention. Public domain.)

(Source: Centers for Disease Control and Prevention. Public domain.)

* Percent of older adults who reported a fall. (Source: Centers for Disease Control and Prevention. Older adult falls:--a growing problem that can be prevented. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2018. Public domain.)

* Percent of older adults who reported a fall. (Source: Centers for Disease Control and Prevention. Older adult falls:--a growing problem that can be prevented. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2018. Public domain.)

* Percent of older adults who reported a fall. (Source: Centers for Disease Control and Prevention. Older adult falls:--a growing problem that can be prevented. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2018. Public domain.)

(Source: Centers for Disease Control and Prevention. Older adult falls:--a growing problem that can be prevented. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2018. Public domain.)

Behavioral Risk Factor Surveillance System, United States, 2012. (Source: Barbour KE, Stevens JA, Helmick CG, et al. Falls and fall injuries among adults with arthritis--United States, 2012. MMWR Morb Mortal Wkly Rep 2014;63[17]:379-83. Public domain.)

(Source: Centers for Disease Control and Prevention/STEADI [Stopping Elderly Accidents, Deaths, and Injuries]. Public domain. Modified slightly by Dr. Douglas J Lanska.)

Note: Data from Michigan, Oregon, and Wisconsin were omitted because of the difference in the way these states collected information about falls during 2012, compared with the rest of the states. Behavioral Risk Factor Surveillance System, United States, 2012–2018. (Source: Moreland B, Kakara R, Henry A. Trends in nonfatal falls and fall-related injuries among adults aged ≥65 years--United States, 2012-2018. MMWR Morb Mortal Wkly Rep. 2020 Jul 10;69[27]:875-81. Public domain.)

Note: Data from Michigan, Oregon, and Wisconsin were omitted because of the difference in the way these states collected information about falls during 2012, compared with the rest of the states. Behavioral Risk Factor Surveillance System, United States, 2012–2018. (Source: Moreland B, Kakara R, Henry A. Trends in nonfatal falls and fall-related injuries among adults aged ≥65 years--United States, 2012-2018. MMWR Morb Mortal Wkly Rep. 2020 Jul 10;69[27]:875-81. Public domain.)

Note: Data from Michigan, Oregon, and Wisconsin were omitted because of the difference in the way these states collected information about falls during 2012, compared with the rest of the states. Behavioral Risk Factor Surveillance System, United States, 2012–2018. (Source: Moreland B, Kakara R, Henry A. Trends in nonfatal falls and fall-related injuries among adults aged ≥65 years--United States, 2012-2018. MMWR Morb Mortal Wkly Rep. 2020 Jul 10;69[27]:875-81. Public domain.)

Note: Data from Michigan, Oregon, and Wisconsin were omitted because of the difference in the way these states collected information about falls during 2012, compared with the rest of the states. Behavioral Risk Factor Surveillance System, United States, 2012-2018. (Source: Moreland B, Kakara R, Henry A. Trends in nonfatal falls and fall-related injuries among adults aged ≥65 years--United States, 2012-2018. MMWR Morb Mortal Wkly Rep. 2020 Jul 10;69[27]:875-81. Public domain.)

(N = 147,319). Injuries resulting from falls are defined as those that caused respondents to limit their regular activities for 1 or more days or to go see a doctor. Behavioral Risk Factor Surveillance System, United States, 2014. (Source: Bergen Bergen G, Stevens MR, Burns ER. Falls and Fall Injuries Among Adults Aged ≥65 Years--United States, 2014. MMWR Morb Mortal Wkly Rep 2016;65:993-8. Public domain.)

(N = 147,319). Behavioral Risk Factor Surveillance System, United States, 2014. (Source: Bergen Bergen G, Stevens MR, Burns ER. Falls and Fall Injuries Among Adults Aged ≥65 Years--United States, 2014. MMWR Morb Mortal Wkly Rep 2016;65:993-8. Public domain.)

The first (shown in green) and last (shown in brown) pure-tone audiograms. Legend: left ear (x) and right ear (o). (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Postoperative resolution of the large ventral epidural fluid collection. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Subsequent tracking of contrast to the right posterior thoracic cord delineating the site of the dural defect, T9-10. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Reverse dynamic CT myelogram demonstrating contrast injection into the ventral epidural collection. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal spine T2-weighted SPC MRI revealed a large ventral epidural fluid collection extending from C3 to L3. (Source: Lobo R, Batbayar B, Kharytaniuk N, et al. Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Neurol Sci 2022;43[9]:5643-6. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the frontal horns (black arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the third ventricle (yellow arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the mesencephalon, suprasellar pons cistern (white arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted gradient echo (GRE) image shows hemosiderin deposits along the peripontine cistern, pons, aqueduct of Sylvius, tentorium, temporal horn of the left lateral ventricle (red arrows). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted axial image shows hemosiderin deposits around the mesencephalon) (blue arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Typical MRI findings in superficial intraventricular surface siderosis. T2-weighted axial image shows hemosiderin deposits along the cerebellar peduncles, around the fourth ventricle (green arrow). (Source: Harizi E, Shemsi K, Ahmetgjekaj I, et al. Superficial intraventricular surface siderosis brain. Radiol Case Rep 2022;17[11]:4152-5. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Dorsolateral view of spinal cord after laminectomy and opening of dura--rotated up to show the ventral dural defect. Legend: A. branch of anterior spinal artery; B. rostral and caudal margins of ventral dural defect with anterior pseudomeningocoele (*) in the depths; C. xanthochromia on spinal cord; D. dentate ligament divided; E. Adhesions to the dural defect, the probable source of chronic subarachnoid hemorrhage. (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

T2-weighted spine MRI in axial (a) and sagittal (b) section shows a longitudinally extensive epidural CSF collection from T2 to T8 (E) with a large spike-like osteophyte at T5/T6 impinging on the dura (G). The CT myelogram (c) shows contrast in the epidural collection from a CSF leak adjacent to the osteophyte (G). Legend: (A) spinal cord coated with hemosiderin; (B) epidural fat, bright on T2; (C) dura posterior to cord; (D) intradural CSF surrounding cord; (E) epidural CSF collection; (F) dura anterior to cord; (G) osteophyte; (H) CSF pulsation artifact. (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Susceptibility-weighted brain MRI (SWI) shows extensive leptomeningeal low signal intensity around the cerebellar folia (a), the basis pontis and vestibulocochlear nerves (b) and Sylvian fissures (c) due to hemosiderin deposition. (Source: Halmagyi GM, Parker GD, Chen L, et al. Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects. Eur Arch Otorhinolaryngol 2023;280[2]:633-41. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (CD68 immunohistochemistry). Superficially located within the cortex, CD68-positive macrophages can be observed (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (GFAP immunohistochemistry). Within the superficial cortex area, iron deposits are accompanied by reactive astrocytes (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (Perls Prussian blue stain). Covering the superficial layers of the cortex, ribbon-like iron deposits are appreciable (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Superficial cortical tissue from the right frontal lobe (H&E). Apart from recent bleeding constituents within the leptomeningeal compartment (arrow), hemosiderin deposits can be seen within the molecular layer of the cortex (arrowheads). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T2-weighted images show intramedullary hyperintense edema and hypointense hemosiderin deposition along the spinal cord surface. The thecal sac shows hypointense blood-fluid levels (left image). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Image shows abnormal linear enhancement along the cord surface and diffuse enhancement of the nerve roots of the cauda equina (-->). (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sequential transverse susceptibility-weighted imaging (SWI) of the brain at the level of the medulla and cerebellum that were acquired over a 64-day period. The progression of the superficial sideroses is visible as a black coating of the brain surface most pronounced on the top of the cerebellum and around the brainstem. (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sequential transverse susceptibility-weighted imaging (SWI) of the brain at the level of the pons, 4th ventricle, and cerebellum that was acquired over a 64-day period. The progression of the superficial sideroses is visible as a black coating of the brain surface most pronounced on the top of the cerebellum and around the brainstem. (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sequential transverse susceptibility-weighted imaging (SWI) of the cerebrum acquired over a 64-day period. The progression of the superficial sideroses is visible as a black coating of the brain surface most pronounced on the top of the cerebellum and around the brainstem. (Source: Friedauer L, Foerch C, Steinbach J, et al. The acute superficial siderosis syndrome: clinical entity, imaging findings, and histopathology. Cerebellum 2023;22[2]:296-304. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up T2-weighted gradient echo (GRE) sagittal image of cervical spinal cord shows severe spinal superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up susceptibility-weighted (SW) transverse image of mesencephalic structures shows severe spinal superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up susceptibility-weighted (SW) transverse image shows severe cortical and periventricular superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

T2-weighted images of cerebellum and brainstem show superficial siderosis. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Sagittal T2-weighted imaging using spectral attenuated inversion recovery (SPAIR) of a myxopapillary ependymoma near the conus terminalis (L3/4). (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Coronal T2-weighted MRI shows left parietal meningioma. (Source: Castro-Gomez S, Binder J, Schievelkamp AH, Heneka MT. CNS superficial siderosis mimicking a motor neuron disease. Brain Sci 2022;12[11]:1558. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Supratentorial superficial siderosis (yellow arrowhead) along the interhemispheric and Sylvian fissures and within temporal and occipital sulci is well demonstrated by the axial susceptibility-weighted (SW) sequence. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Superficial siderosis along the eighth cranial nerves on both sides is clearly seen on an axial gradient echo (GRE) image magnification. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Superficial siderosis along the eighth cranial nerves on both sides is clearly seen on a sagittal TSE T2 image magnification. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Apparent diffusion coefficient (ADC) image shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast susceptibility-weighted image (SWI) shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast gradient echo (GRE) image shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast axial TSE T2 image shows superior cerebellar atrophy (yellow crooked arrow) associated with infratentorial diffuse superficial siderosis (yellow arrowhead), mostly of the pons, cerebellar folia, dentate hila, and superior vermis. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast coronal T2 Fluid-attenuated inversion recovery (FLAIR) image shows superior cerebellar atrophy (yellow crooked arrow). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast sagittal 3D T1 MRI shows superior cerebellar atrophy (yellow crooked arrow). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Sagittal gradient echo (GRE) T2 MRI of the thoracic spine shows extensive superficial siderosis around the spinal cord, from below a dural defect up to the medullary cone. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Axial CT image through the T6-T7 disc shows a dural defect just to the right of midline at the level of the spur and further delineates the associated ventral epidural fluid collection. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Axial T1-weighted MRI through the T6-T7 disc shows a dural defect just to the right of midline at the level of the spur and further delineates the associated ventral epidural fluid collection. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Axial turbo-spin echo (TSE) T2 MRI through the T6-T7 disc shows a dural defect just to the right of midline at the level of the spur and further delineates the associated ventral epidural fluid collection. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

CT in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. The noncontrast sagittal spinal CT image shows a partially calcified disc extrusion also recognizable by noncontrast sagittal spinal CT images. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Sagittal T1-weighted MRI of the cervical and upper thoracic spine shows an anterior wedge degenerative deformation of the T6 vertebral body with a superimposed prominent central disc extrusion characterized by osteo-calcific signal (yellow arrow) causing a dural tear at the T6-T7 level. Above the disc extrusion, note the “sentinel” epidural fluid collection (red asterisk) stretching along the ventral aspect of the spinal canal and displacing the dura posteriorly. (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Sagittal turbo-spin echo (TSE) T2 MRI of the cervical and upper thoracic spine shows an anterior wedge degenerative deformation of the T6 vertebral body with a superimposed prominent central disc extrusion characterized by osteo-calcific signal (yellow arrow) causing a dural tear at the T6-T7 level. Above the disc extrusion, note the “sentinel” epidural fluid collection (red asterisk) stretching along the ventral aspect of the spinal canal and displacing the dura posteriorly. TSE T2 MRI shows low signal intensity along the surface of the spinal cord consistent with superficial siderosis (yellow arrowhead). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI in a 69-year-old woman with slowly progressive gait disturbances and hearing impairment. Noncontrast sagittal constructive interference in steady state (CISS) MRI of the cervical and upper thoracic spine shows an anterior wedge degenerative deformation of the T6 vertebral body with a superimposed prominent central disc extrusion characterized by osteo-calcific signal (yellow arrow) causing a dural tear at the T6-T7 level. Above the disc extrusion, note the “sentinel” epidural fluid collection (red asterisk) stretching along the ventral aspect of the spinal canal and displacing the dura posteriorly. CISS MRI shows low signal intensity along the surface of the spinal cord consistent with superficial siderosis (yellow arrowhead). (Source: Bonomo G, Cusin A, Rubiu E, et al. Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis. Neurol Sci 2022;43[7]:4167-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

C and D are the left and right sides, respectively, of the same patient. (Source: Artukarslan E, Matin F, Donnerstag F, Gärtner L, Lenarz T, Lesinski-Schiedat A. Cochlea implantation in patients with superficial hemosiderosis. Eur Arch Otorhinolaryngol 2022;279[9]:4363-70. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial T2-weighted MRI indicates siderosis of the quadrigeminal plate (double white arrows) and the upper cerebral vermis (white arrowheads) with sparing of the cortex of both temporal lobes (curved white). (Source: Artukarslan E, Matin F, Donnerstag F, Gärtner L, Lenarz T, Lesinski-Schiedat A. Cochlea implantation in patients with superficial hemosiderosis. Eur Arch Otorhinolaryngol 2022;279[9]:4363-70. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Axial T2-weighted MRI indicates siderosis of the cranial nerves VII, VIII, and IX from their pontine emergence up to the entry in the inner auditory canal (white arrows) and the cerebellar cortex (white arrowheads). (Source: Artukarslan E, Matin F, Donnerstag F, Gärtner L, Lenarz T, Lesinski-Schiedat A. Cochlea implantation in patients with superficial hemosiderosis. Eur Arch Otorhinolaryngol 2022;279[9]:4363-70. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Li M, Shan B, Peng X, Chang H, Cui L. An urgent health problem of indoor air pollution: results from a 15-years carbon monoxide poisoning observed study in Jinan City. Sci Rep 2023;13[1]:1619. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Li M, Shan B, Peng X, Chang H, Cui L. An urgent health problem of indoor air pollution: results from a 15-years carbon monoxide poisoning observed study in Jinan City. Sci Rep 2023;13[1]:1619. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Li M, Shan B, Peng X, Chang H, Cui L. An urgent health problem of indoor air pollution: results from a 15-years carbon monoxide poisoning observed study in Jinan City. Sci Rep 2023;13[1]:1619. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Li M, Shan B, Peng X, Chang H, Cui L. An urgent health problem of indoor air pollution: results from a 15-years carbon monoxide poisoning observed study in Jinan City. Sci Rep 2023;13[1]:1619. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Li M, Shan B, Peng X, Chang H, Cui L. An urgent health problem of indoor air pollution: results from a 15-years carbon monoxide poisoning observed study in Jinan City. Sci Rep 2023;13[1]:1619. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Li M, Shan B, Peng X, Chang H, Cui L. An urgent health problem of indoor air pollution: results from a 15-years carbon monoxide poisoning observed study in Jinan City. Sci Rep 2023;13[1]:1619. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Rates per 100,000 inhabitants and age-standardized to the 2013 European Standard Population. Error bars show the 95% confidence intervals. The Carstairs Index is a composite measure of unemployment, household overcrowding, car ownership, and social class. Carstairs scores (a score of 1 corresponding to the least deprived area) were standardized at local geographic levels and categorized into quintiles for the analysis. The local geographic levels were based on British census groupings and comprised between 2000 and 6000 households, with a resident population between 5000 and 15,000 persons. (Sources: Carstairs V, Morris R. Deprivation and mortality: an alternative to social class? Community Med 1989;11[3]:210-19. Roca-Barcelo A, Crabbe H, Close R, Fahie H, Leonardi GS, Piel FB. Spatial and temporal trends and risk factors for intentional carbon monoxide poisoning hospitalizations in England between 2002 and 2016. J Affect Disord 2023;329:168-75. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Bars show the age-standardized rates (left y-axis). Dashed lines reflect number of cases (right y-axis). Counts under 10 have been suppressed, hence, the interrupted lines. Population standardized to the 2013 European Standard Population. (Source: Roca-Barcelo A, Crabbe H, Close R, Fahie H, Leonardi GS, Piel FB. Spatial and temporal trends and risk factors for intentional carbon monoxide poisoning hospitalizations in England between 2002 and 2016. J Affect Disord 2023;329:168-75. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The scale is presented on the left y-axis. Shaded areas indicate 95% confidence intervals. Dashed lines present the age-standardized suicide rate, regardless of method, by gender in England with the corresponding scale on the right y-axis. Population standardized to the 2013 European Standard Population. (Source: Roca-Barcelo A, Crabbe H, Close R, Fahie H, Leonardi GS, Piel FB. Spatial and temporal trends and risk factors for intentional carbon monoxide poisoning hospitalizations in England between 2002 and 2016. J Affect Disord 2023;329:168-75. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

The line shows the 3-month moving average. Data include records of visits to any nonfederal hospital facility in Maine, including records of all outpatient and emergency department visits billed through a nonfederal hospital in Maine. (Source: CDC/Graber JM, Smith AE. Results from a state-based surveillance system for carbon monoxide poisoning. Public Health Rep 2007;122[2]:145-54. Public domain.)

Leyden jars and other apparatus used by Aldini in experiments, which were intended to support his uncle, Galvani, against the attacks of Volta. (Source: Plate 4. Aldini J. An account of the late improvements in galvanism, with a series of curious and interesting experiments performed before the commissioners of the French National Institute, and repeated lately in the anatomical theatres of London: To which is added, an appendix, containing the author’s experiments on the body of a malefactor executed at Newgate. &c. &c. illustrated with engravings. London: Wilks and Taylor, 1803.)

"On the power of galvanism as applied to medicine." Selected experiments as reported by Aldini in 1803, when he summarized experiments and demonstrations over the prior decade.

(Fig. 1) “I have had few opportunities of applying Galvanism in diseases of the organs of hearing. ... One extremity of the lever which forms the communication, is fixed to the base or negative end of the pile, and the other terminates in a small hammer, so placed as to strike a bell, which by means of a bason of water is in communication with certain parts of the patient, while an arc extends from the patient to the summit or positive end of the pile. In consequence of this arrangement, every time that the small hammer strikes the bell the Galvanic action of the pile is repeated. In cases of deafness, I cause the patient to hold in one hand an insulated metallic arc, one end of which is brought into contact with the affected ear, and the other with the positive end of the pile; and to immerse the other hand in a bason [sic, basin] of salt water placed above the bell. When this disposition has been made, the wheel-work is turned round, which gives motion to the lever; and every time that the hammer strikes the bell, a communication is formed between the positive and negative ends of the pile: consequently there will then be a circulation of the fluid, and the Galvanism will exercise a direct action on the organ of hearing."

(Fig. 3) "But as I observed that the action of Galvanism on the ears was sometimes too violent, we thought proper to apply it in a more moderate and less dangerous manner. Several persons having been induced through curiosity to try this action, the result, besides a violent commotion of the whole substance of the brain against the skull, was a state of watchfulness which continued several days running, and which I experienced myself as well as others. We then conceived the idea of shaving the head above the suture of the parietal bone; and having moistened the shaven part with salt water, a piece of gold or silver coin was placed over it. The patient then touched with one of his hands the bottom of the pile, and at the same time an arc was established from the summit of the pile to the metallic armature placed on the head. By this arrangement the action of the Galvanism was rendered more moderate; the patient endured it for a long time, and seemed to be greatly relieved by it."

(Source: Plate 3. Aldini J. An account of the late improvements in galvanism, with a series of curious and interesting experiments performed before the commissioners of the French National Institute, and repeated lately in the anatomical theatres of London: To which is added, an appendix, containing the author’s experiments on the body of a malefactor executed at Newgate. &c. &c. illustrated with engravings. London: Wilks and Taylor, 1803.)

Selected experiments as reported by Aldini in 1803, when he summarized experiments and demonstrations over the prior decade.

(Fig. 1) "The head of an ox, recently killed, was subjected to the action of a [voltaic] pile [ie, a batterhy] composed of fifty plates of copper and zinc, separated, as usual, by small pieces of pasteboard moistened with a solution of muriate of soda [ie, common salt, sodium chloride, to facilitate conduction]. Having moistened one of the ears with the same solution, by means of a syringe, I introduced into it one extremity of a metallic wire. I then formed an arc with this wire to the summit of the pile, and by means of another wire made a communication between the bottom of the pile and the nostrils. When this apparatus was applied, the eyes were seen to open, the ears to shake, the tongue to be agitated, and the nostrils to swell, in the same manner as those of the living animal, when irritated and desirous of combating another of the same species. I then moistened both the ears with salt water, by the same method as before, and inserted into each an extremity of one of the arcs. When the Galvanism was communicated, the movements already described were reproduced; but they appeared to be much more violent."

(Fig. 2) "A pile composed of a hundred pieces of silver and zinc being employed, the tongue issued from the mouth four inches, and re-entered it an inch, on each application of the arc; notwithstanding the resistance opposed by the teeth which pressed against it: so that after four or five applications of the arc it was entirely restored to its usual situation."

(Fig. 4) "The head and trunk of a dog, separated from each other, and placed in such a manner as to leave an interval of about a foot between them, were made to move simultaneously by applying the Galvanic action to one of the ears, and to a small incision made in one of the extremities of the trunk."

(Source: Plate 2. Aldini J. An account of the late improvements in galvanism, with a series of curious and interesting experiments performed before the commissioners of the French National Institute, and repeated lately in the anatomical theatres of London: To which is added, an appendix, containing the author’s experiments on the body of a malefactor executed at Newgate. &c. &c. illustrated with engravings. London: Wilks and Taylor, 1803.)

Selected experiments as reported by Aldini in 1803, when he summarized experiments and demonstrations over the prior decade.

(Fig. 1, bottom left): "Having provided the head of an ox, recently killed, I thrust a finger of one of my hands, moistened with salt water, into one of the ears, at the same time that I held a prepared frog in the other hand, in such a manner that its spinal marrow touched the upper part of the tongue. When this arrangement was made, strong convulsions were observed in the frog; but on separating the arc all the contractions ceased."

(Fig. 3, bottom right): "Having placed the trunk of a calf on an insulated table, I made a longitudinal incision in the breast, in order to obtain a long series of muscles uncovered. I then arranged two insulated persons in such a manner that the one with a finger, moistened by salt water, touched the spinal marrow of the calf, while the other applied the spinal marrow of a frog to the muscles of the trunk. Every time this arc was formed, muscular contractions were produced in the frog. When the two persons let go each other’s hands, the contractions ceased. I repeated this experiment, with the same success, on the insulated head of an ox, conveying the arc from the spinal marrow of the frog to the tongue. Frogs were as violently affected when the experiment was made with the insulated trunks of different kinds of birds. This experiment, in my opinion, affords a decisive proof that the Galvanic fluid is peculiar to the animal machine, independently of the influence of metals, or of any other foreign cause."

(Source: Plate 1. Aldini J. An account of the late improvements in galvanism, with a series of curious and interesting experiments performed before the commissioners of the French National Institute, and repeated lately in the anatomical theatres of London: To which is added, an appendix, containing the author’s experiments on the body of a malefactor executed at Newgate. &c. &c. illustrated with engravings. London: Wilks and Taylor, 1803.)

"Electrocution" (1917). Lithograph. (Source: Library of Congress Prints and Photographs Division Washington, DC. Public domain.)

The man at the table (back right) is pushing a button to signal that all is prepared for the execution. (Source: Scientific American 1888;58-59:407. Public domain.)

(Source: NYPL Digital Gallery. Public domain.)

(Source: George Eastman House Collection. Public domain.)

(Public domain.)

(Courtesy of the Wellcome Trust. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Some of Galvani's experiments (Plate III) from his De Viribus Electricitatis in Motu Musculari Commentarius (Commentary on the Effects of Electricity on Muscular Motion, 1792). (Courtesy of the Wellcome Trust. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Some of Galvani's experiments (Plate II) from his De Viribus Electricitatis in Motu Musculari Commentarius (Commentary on the Effects of Electricity on Muscular Motion, 1792). (Courtesy of the Wellcome Trust. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Some of Galvani's experiments (Plate I) from his De Viribus Electricitatis in Motu Musculari Commentarius (Commentary on the Effects of Electricity on Muscular Motion, 1792). Various frog preparations are shown as well as special devices designed by Galvani for his experiments, notice the presence of an electrostatic machine (left) and a Leyden jar (right). (Courtesy of the Wellcome Trust. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

Pulitzer Prize-winning photograph by Rocco Morabito. Photograph on July 17, 1967, of utility lineman Jimmy Thompson giving mouth-to-mouth resuscitation to fellow worker RG Champion after Champion was knocked unconscious by an electric shock. Originally published in the Jacksonville Journal on July 18, 1967. Winner of the 1968 Pulitzer Prize for Spot News Photography. (This work is in the public domain in the United States because it was published in the United States between 1928 and 1977, inclusive, without a copyright notice. See also: Soergel M. 50 years later, “Kiss of Life” photo still stops people in their tracks. The Florida Times-Union. July 16, 2017.)

German polymath Friedrich Heinrich Alexander von Humboldt. Lithograph by C. Wildt after C Begas, 1840. (Courtesy of the Wellcome Trust. Creative Commons Attribution 2.0 Generic [CC BY] license, creativecommons.org/licenses/by/2.0/deed.en.)

(Public domain.)

Probably made and used by Volta himself. This pile was shown at the exhibition at Como, Italy in 1899, commemorating the work of Galvani and Volta. (Courtesy of the Wellcome Trust. Creative Commons Attribution 2.0 Generic [CC BY] license, creativecommons.org/licenses/by/2.0/deed.en.)

Stipple engraving by A Tardieu after N Bettoni. (Courtesy of the Wellcome Trust. Public domain.)

(Source: De viribus electricitatis in motu musculari [Galvani 1791, Plate 4].)

(Source: De viribus electricitatis in motu musculari [Galvani 1791, Plate 3].)

Galvani's experiments with atmospheric electricity of a stormy day with antenna-like wires connected with the spinal cords of decapitated frogs. (Source: De viribus electricitatis in motu musculari [Galvani 1791, Plate 2].)

Galvani's experiments with static electricity transmitted to the spinal cords of decapitated frogs. Some of the frog legs are open to the air, and others are sealed in jars but still connected to wires passing through a cork at the top. Note the electrostatic machine (left table top) charging a disembodied hand. Note also the Leyden jar on the table (right). (Source: De viribus electricitatis in motu musculari [Galvani 1791, Plate 1].)

Lithograph depicts Italian physician, anatomist, and physiologist Luigi Galvani (1737-1798). (Courtesy of the Wellcome Trust. Creative Commons Attribution 2.0 Generic [CC BY] license, crea tivecommons.org/licenses/by/2.0/deed.en.)

Dutch scientist Pieter van Musschenbroek of Leiden (Leyden), Netherlands c1745-1746 (Allerhand 2018) and his student Andreas Cunaeus performing electrical experiments. (Source: Print from a steel engraving by Christiaan Lodewijk van Kesteren [1832-1897] done c1865-1870 after a painting by Dutch painter David Adolph Constant Artz [1837-1890]. Historische Galerij der Maatschappij Arti et Amicitiae [Historical Gallery of the Art and Friendship Society]. Courtesy of the Rijkmuseum, Amsterdam. Public domain. Image cropped from the original.)

Artist's conception of the discovery of the Leyden jar by Cunaeus and Muschenbroek, apparently in late 1845. Andreas Cunaeus, a pupil of Pieter von Muschenbroek in Leyden, attempted to "condense" electricity in a glass of water. The rotating glass sphere (right) is an electrostatic machine. The static electricity generated by the hands rubbing on it is transferred through the chain to the suspended metal bar, and from it via the hanging wire into the glass of water. The glass acted as a capacitor; a large charge built up in the water, and an equal charge of the opposite polarity built up in Cunaeus' hand holding the glass. When Cunaeus reached up to pull the wire out of the water, he got a severe shock, much worse than an electrostatic machine could give, because the amount of charge stored was much larger than the terminal of an electrostatic machine could store. Cunaeus took 2 days to recover. Musschenbroek was similarly impressed by the powerful shock he received from the device. Reports of the experiment were widely circulated, and scientists began to investigate the charge storage ability of these "Leyden flasks." Eventually the water was replaced by foil coatings on the inside and outside of the jar to store the charge. (Source: Deschanel AP. Elementary Treatise on Natural Philosophy. Part 3: Electricity and Magnetism. Translated and edited by JD Everett. New York: D. Appleton and Co., 1876:570. Figure 382. Public domain.)

Capacitance discharge of a Leyden jar onto a man, possibly Dutch scientist Pieter van Musschenbroek or his student Andreas Cunaeus. (Source: Winkler JH. Der Stärke der Elektrischen Kraft des Wassers in Gläsernen Gefässen. Leipzig: Berhard Christoph Breittopf, 1746.)

(Source: Stefan Reitzner [2006]. Creative Commons Attribution-Share Alike 2.0 Germany [CC BY-SA 2.0 DE] license, creativeco mmons.org/licenses/by-sa/2.0/de/deed.en. Cropped from original.)

Current flows through the body from the entrance point, until finally exiting where the body is closest to the ground. This foot suffered massive internal injuries, which weren't readily visible, and the foot had to be amputated a few days later. (Source: Occupational Safety and Health Administration via Wikimedia Commons. Public domain.)

Electrical burns may show erythema and bullae from the heat of arcing current or may be nondescript with severe internal damage between the points of contact and exit of the current. (Source: National Institute for Occupational Safety and Health [NIOSH] via Wikimedia Commons. Public domain.)

Spark-gap radio transmitter for a long-distance wireless telegraphy radio station built by Gesellshaft fur Drahtlose Telegraphie (Telefunken) at Nauen, Germany in 1907. Designed by German radio pioneer Georg von Arco (1869-1940), this was Germany's first high-power radio station and (using a more powerful transmitter) served as Germany's main communication channel with other nations during World War I. The bank of 360 narrow Leyden jar capacitors is visible in the background. The jars have a total capacitance of 400 microfarads. The station was powered by an oil engine turning a 35 horsepower (26 kilowatts) alternator. The transmitter's radiated power was about 10 kW in the very low frequency band using a 300-foot high-wire umbrella antenna; it could be received at a range of about 3,500 kilometers (2,200 miles). (Source: Monckton CC. Radio-Telegraphy. D Van Nostrand Co.: New York, 1908:228. Figure 155. Also published in Ramakers L. The new wireless station at Nauen Germany. Scientific American supplement 1907;63[1621]:25972. Figure 1. Public domain.)

(Source: Bertholon P. De l'électricité du corps humain dans l'état de santé et de maladie. Ouvrage couronné par l'Académie de Lyon, dans lequel on traite de l'electricité de l'atmosphere ... / par m. l'abbé Bertholon. A Paris: Chez Croulbois ...; Et à Lyon: Chez Bernuset ..., 1786. Courtesy of the Wellcome Trust. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

A Leyden jar, with electrical charge signs added to the original drawing. (Source: Marchant WH. Wireless Telegraphy: A Handbook for the Use of Operators and Students. Whittaker and Co.: New York, 1914:7. Figure 6. Public domain.)

Portrait of Benjamin Franklin with his kite in the background. After a painting by Benjamin West (1738-1820) done c1816 after Franklin had died. This dramatic painting commemorates the 1752 experiment in Philadelphia in which Franklin demonstrated that lightning is a form of electricity. While in London, West had befriended Franklin but did not paint this image until after Franklin had died. The painting was a study for a larger, unrealized portrait that West planned to give to the Pennsylvania Hospital, an institution Franklin had cofounded in 1751 with physician and surgeon Dr. Thomas Bond (1713-1784). (Source: Wellcome Trust. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0/deed.en.)

A 29-year-old no with no previous neurologic disease and a history of schizophrenia and refractory psychosis on clozapine developed nonconvulsive status epilepticus after electroconvulsive therapy. Last EEG (sensitivity is 7 μV/mm) before the discharge. (Source: Saltoğlu T, Şenol B, Koc G. Non-convulsive status epilepticus as a complication of electroconvulsive therapy: a case report and review of the literature. Cureus 2023;15[3]:e35639. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 29-year-old no with no previous neurologic disease and a history of schizophrenia and refractory psychosis on clozapine developed nonconvulsive status epilepticus after electroconvulsive therapy. In the second EEG (sensitivity is 7 μV/mm) under the treatment with midazolam, no abnormal activity was seen. (Source: Saltoğlu T, Şenol B, Koc G. Non-convulsive status epilepticus as a complication of electroconvulsive therapy: a case report and review of the literature. Cureus 2023;15[3]:e35639. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

A 29-year-old with no previous neurologic disease and a history of schizophrenia and refractory psychosis on clozapine developed nonconvulsive status epilepticus after electroconvulsive therapy. First EEG (sensitivity is 7 μV/mm) showed right temporal rhythmic delta activity spreading to the left homolog area three seconds later with an increase in amplitude. This activity lasted 15 seconds. (Source: Saltoğlu T, Şenol B, Koc G. Non-convulsive status epilepticus as a complication of electroconvulsive therapy: a case report and review of the literature. Cureus 2023;15[3]:e35639. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Courtesy of Wikimedia Commons User: Junglecat [2008]. Creative Commons Attribution-Share Alike 3.0 Unported license, creativecommons.org/licenses/by-sa/3.0/deed.en.)

(Photograph by Marek Peters [www.marek-peters.com]. GNU Free Documentation License, Version 1.2.)

MRI FLAIR sequence showing extensive white matter signal abnormality (red arrows) in a 53-year-old woman who had touched a live antenna at age 8 with electrical injury and loss of consciousness. (Source: Jacobs J, Price K, Lagman M, Shreya J, Liu AK. Bilateral diffuse leukoencephalopathy in an electrocuted patient where the brain was not in the pathway of conduction. Cureus 2023;15[1]:e33771. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI FLAIR sequence showing extensive signal abnormality in the white matter (red arrows) in a 53-year-old woman who had touched a live antenna at age 8 with electrical injury and loss of consciousness. (Source: Jacobs J, Price K, Lagman M, Shreya J, Liu AK. Bilateral diffuse leukoencephalopathy in an electrocuted patient where the brain was not in the pathway of conduction. Cureus 2023;15[1]:e33771. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

MRI FLAIR sequence showing white matter signal abnormality (red arrows) sparing midbrain (blue circle) in a 53-year-old woman who had touched a live antenna at age 8 with electrical injury and loss of consciousness. (Source: Jacobs J, Price K, Lagman M, Shreya J, Liu AK. Bilateral diffuse leukoencephalopathy in an electrocuted patient where the brain was not in the pathway of conduction. Cureus 2023;15[1]:e33771. Creative Commons Attribution [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Czechoslovakian electrical accident poster (1926). The Czechoslovak Electrotechnical Union (ESČ) published a series of around 30 "Accident Posters" by Ing. Š. Andrýska dated 1926. (Source: Edice umělecké reklamy Jana Zieglrose [Jan Zieglros edition of artistic advertising]. Public domain.)

Czechoslovakian electrical accident poster (1926). Top left: "correct." Top right: "wrong." The Czechoslovak Electrotechnical Union (ESČ) published a series of around 30 "Accident Posters" by Ing. Š. Andrýska dated 1926. (Source: Edice umělecké reklamy Jana Zieglrose [Jan Zieglros edition of artistic advertising]. Public domain.)

Czechoslovakian electrical accident poster (1926). The Czechoslovak Electrotechnical Union (ESČ) published a series of around 30 "Accident Posters" by Ing. Š. Andrýska dated 1926. (Source: Edice umělecké reklamy Jana Zieglrose [Jan Zieglros edition of artistic advertising]. Public domain.)

Czechoslovakian electrical accident poster (1926). The Czechoslovak Electrotechnical Union (ESČ) published a series of around 30 "Accident Posters" by Ing. Š. Andrýska dated 1926. (Source: Edice umělecké reklamy Jana Zieglrose [Jan Zieglros edition of artistic advertising]. Public domain.)

Czechoslovakian electrical accident poster (1926) showing the risk of electrical injury from attempted repair of electrical outlets or electrically powered devices without first interrupting the electrical source. The Czechoslovak Electrotechnical Union (ESČ) published a series of around 30 "Accident Posters" by Ing. Š. Andrýska dated 1926. (Source: Edice umělecké reklamy Jana Zieglrose [Jan Zieglros edition of artistic advertising]. Public domain.)

Czechoslovakian electrical accident poster (1926) showing the risk of electrical injury from contact with electrical sources while bathing. The Czechoslovak Electrotechnical Union (ESČ) published a series of around 30 "Accident Posters" by Ing. Š. Andrýska dated 1926. (Source: Edice umělecké reklamy Jana Zieglrose [Jan Zieglros edition of artistic advertising]. Public domain.)

Benjamin Franklin holds a book titled Electric Exp[erimen]ts, with scientific instruments to his left and with lightning striking a village in the background. Engraving by James McArdell (approximately 1729-1765 from a painting by Benjamin Wilson (1721-1788). Franklin sat for Wilson, who also experimented with electricity, shortly after his arrival in London. Franklin worked in London as a foreign diplomat representing the Pennsylvania Assembly. (Source: Gardiner Greene Hubbard Collection [Library of Congress]. Library of Congress Prints and Photographs Division Washington DC. Public domain.)

Legend: AdoCbl, adenosylcobalamin; Cys, cystine; Cyst, cystathionine; Hcy, homocysteine; MeCbl, methyladenosylcobalamin; Met cycle, methionine cycle; MCM, methylmalonyl-CoA mutase; MMA, methylmalonic acid; MS, methionine synthase; MTHF, N5-methyltetrahydrofolate; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; TCA cycle, tricarboxylic acid cycle; THF, tetrahydrofolate. (Source: Lipari Pinto P, Florindo C, Janeiro P, et al. Acquired vitamin B12 deficiency in newborns: positive impact on newborn health through early detection. Nutrients 2022;14[20]:4397. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Partial atrophic glossitis in a 58-year-old woman with the chief complaint of a burning sensation on the tongue for 6 months. She was easily fatigued for several months and denied any systemic diseases. Her serum vitamin B12 level was 72 ng/L (normal range 180 to 914 ng/L), and serum levels of folate, ferritin, and hemoglobin were all within the normal range. (A) Physical examination revealed partial atrophy of the tongue. (B) Complete resolution after 1 month of supplement therapy. (C) The therapeutic effect was still evident during follow-up at 6 months. (Source: Chen GY, Tang ZQ, Bao ZX. Vitamin B12 deficiency may play an etiological role in atrophic glossitis and its grading: a clinical case-control study. BMC Oral Health 2022;22[1]:456. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Functional connectivity networks of the right- and left-sided lesions of the posterior insula that did not lead to vertigo/dizziness (n=10 cases). The functional connectivity network observed in these lesions was remarkably similar, involving the vestibulo-cerebellum and the cortical vestibular and ocular motor networks. The color bar shows t score intensities. Abbreviations: IX, X cerebellar lobules IX, X, MT+ motion-sensitive temporal area, PIVC parieto-opercular (retro-) insular vestibular cortex, PIC posterior insular cortex, FEF frontal eye field, CEF cingulate eye field, LIP/VIP lateral/ventral intraparietal area, CsV cingulate visual sulcus. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Overlap of functional connectivity networks of the individual lesions in published case reports on hemispheric infarcts accompanied by vertigo (positive correlations with the lesion site). The figure shows an overlap of eight or more cases. Common vestibular network hubs to all lesions include the cerebellar vestibular and ocular motor representations in lobules IX (nodulus, uvula); lobule X (flocculus/paraflocculus); the vestibular nuclei (VN); the thalamus; the parieto-insular vestibular cortex (PIVC), which includes insular gyri IV, V (anterior and posterior long insular gyri), area OP2, and retro-insular cortex; the posterior insular cortex (area PIC); motion-sensitive temporal and cingulate areas MT + and CSv (cingulate visual area); ocular motor and vestibular intraparietal areas LIP and VIP (lateral and ventral intraparietal area); and the frontal and cingulate eye fields (FEF, CEF). The color bar gives the number of overlapping lesion functional connectivity networks. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Disconnectome map of all 10 lesions that manifested with vertigo from published case reports on hemispheric infarcts. Disconnectome results are shown with a threshold at 0.5 (greater than 50% probability of disconnection). Disconnection was observed for the posterior fronto-insular tracts (IV, V) that connect the posterior insula with the opercula. Intra-hemispheric disconnection affected the arcuate fascicle and the superior longitudinal fascicle (SLF, mostly third branch). (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

In rare cases, the lesions (from published case reports on hemispheric infarcts accompanied by vertigo) involved vestibular structures in the parietal operculum (OP2), the intraparietal sulcus (area VIP), and the temporal lobe (MT+). None of the lesions directly affected the posterior insular cortex (PIC) although lesion 5 is close to this structure. Abbreviations: OP2 parietal operculum 2; MT+, motion-sensitive middle temporal area; VIP ventral intraparietal area; PIC posterior insular cortex, IV anterior long insular gyrus, V posterior long insular gyrus. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Overlap image of ischemic infarcts involving the insula (overlap of at least two lesions is depicted) from published case reports on hemispheric infarcts accompanied by vertigo: the ischemic lesions were mainly located in the posterior parts of the insula (anterior long insular gyrus and posterior long insular gyrus--IV, V). (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Representative axial slices for each lesion of published case reports on hemispheric infarcts accompanied by vertigo (lesions 1-10) and infarcts that did not present with vertigo (lesion overlap of 10 cases; 11-12). Left-sided lesions with vertigo are shown in the top row. (Source: Conrad J, Boegle R, Ruehl RM, Dieterich M. Evaluating the rare cases of cortical vertigo using disconnectome mapping. Brain Struct Funct 2022;227[9]:3063-73. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Perfusion CT showed that the perfusion deficits remained in the left cerebellum along the PICA and AICA territories (red arrow). (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Pure-tone audiogram documented persistent left sensorineural hearing loss with a pure-tone average of 53 dB on follow-up 2 months after treatment for sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow-up diffusion-weighted imaging and apparent diffusion coefficient mapping performed 3 days after onset of sudden unilateral hearing loss and vertigo demonstrated multifocal infarctions along the posterior circulation involving the upper cerebellum and occipital lobe. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Brain CT angiography revealed occlusion of the left intracranial vertebral artery distal to the posterior inferior cerebellar artery (PICA) and multifocal stenosis of the right intracranial vertebral artery, suspicious for bilateral vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Perfusion-weighted imaging revealed left posterior inferior cerebellar artery and anterior inferior cerebellar artery territorial perfusion deficits without infarction in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Normal apparent diffusion coefficient map in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Normal diffusion-weighted imaging in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Pure tone audiogram showing mild left sensorineural hearing loss in a 51-year-old man with sudden unilateral hearing loss and vertigo due to vertebral artery dissections. (Source: Kim YS, Tehrani AS, Lee HS. Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection. BMC Neurol 2022;22[1]:489. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Deficiency leads to raised muscle protein breakdown via the ubiquitin-proteasomal pathway (UPP) and autophagy and upregulation of AMPK and members of the renin-angiotensin system. Whilst unclear, low vitamin D states may lead to impaired mitochondrial function and increased adiposity in muscle. Permanent withdrawal from the cell cycle (senescence) is a key phenomenon in aging, and the vitamin D/VDR axis has regulatory control. Abbreviations: 25(OH)D3, 25-hydroxyvitamin D; AMPK, 5′ adenosine monophosphate-activated protein kinase; SASP, senescence associated-secretory phenotype; Ca2+, calcium ion; FFA, free fatty acids; PPARγ, peroxisome proliferator-activated receptor gamma. (Source: Bollen SE, Bass JJ, Fujita S, Wilkinson D, Hewison M, Atherton PJ. The Vitamin D/vitamin D receptor (VDR) axis in muscle atrophy and sarcopenia. Cell Signal 2022;96:110355. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Plantone D, Primiano G, Manco C, Locci S, Servidei S, De Stefano N. Vitamin D in neurological diseases. Int J Mol Sci 2022;24[1]:87. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Ab--amyloid b; BDNF--brain-derived neurotrophic factor; DA--dopamine; DAT--dopamine transporter; DOPAC--3,4-dihydroxyphenylacetic acid; GDNF--glial-derived neurotrophic factor; HVA--homovanillic acid; NGF--nerve growth factor; ROS--reactive oxygen species; Syn--synuclein; TH--tyrosine kinase; VDR-- the vitamin D receptor. (Source: Lasoń W, Jantas D, Leśkiewicz M, Regulska M, Basta-Kaim A. The vitamin D receptor as a potential target for the treatment of age-related neurodegenerative diseases such as Alzheimer's and Parkinson's diseases: a narrative review. Cells 2023;12[4]:660. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Subsequent angiographic images of the vertebrobasilar arterial network after catheterization of the left subclavian artery and contrast media instillation. Blood flows through the left vertebral artery (A), partly supplies the basilar artery (B, C), but preferentially runs back through the right vertebral artery towards the right subclavian artery (B, C, and D) depicting a crossed subclavian-vertebral steal syndrome. Arrow: left vertebral artery. (Source: Filis K, Toufektzian L, Sigala F, et al. Right subclavian double steal syndrome: a case report. J Med Case Rep 2008;2:392. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Angiography after catheterization of the innominate artery near the origin of the right common carotid and subclavian arteries demonstrating occlusion of the brachiocephalic trunk (bold black arrow). Contrast media does not pass into the right vertebral artery due to the retrograde blood flow in the vessel (subclavian-vertebral steal syndrome). Concomitant stenosis of the common carotid artery (thin black arrow) is a manifestation of generalized atherosclerotic disease. White arrow: pacemaker wire. (Source: Filis K, Toufektzian L, Sigala F, et al. Right subclavian double steal syndrome: a case report. J Med Case Rep 2008;2:392. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Duplex ultrasonography of the right internal carotid artery depicting the biphasic antegrade blood flow during cardiac systole and retrograde blood flow towards the right subclavian artery during cardiac diastole (subclavian-carotid steal syndrome). The patient was a 73-year-old man who presented for the evaluation of dizziness and episodes of syncope and was found to have right subclavian double steal syndrome. Innominate artery occlusion proximal to the origin of the common carotid and vertebral arteries may result in retrograde blood flow in one or both of these vessels and preferential blood flow into the low-pressure ipsilateral arm vessels during exercise (or even at rest), depending on the presence of collateral flow and on the relative resistance of the vascular beds. (Source: Filis K, Toufektzian L, Sigala F, et al. Right subclavian double steal syndrome: a case report. J Med Case Rep 2008;2:392. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Duplex ultrasonography of the right common carotid artery depicting the biphasic antegrade blood flow during cardiac systole and retrograde blood flow towards the right subclavian artery during cardiac diastole (subclavian-carotid steal syndrome). The patient was a 73-year-old man who presented for the evaluation of dizziness and episodes of syncope and was found to have right subclavian double steal syndrome. Innominate artery occlusion proximal to the origin of the common carotid and vertebral arteries may result in retrograde blood flow in one or both of these vessels and preferential blood flow into the low-pressure ipsilateral arm vessels during exercise (or even at rest), depending on the presence of collateral flow and on the relative resistance of the vascular beds. (Source: Filis K, Toufektzian L, Sigala F, et al. Right subclavian double steal syndrome: a case report. J Med Case Rep 2008;2:392. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/2.0.)

Diffusion-weighted imaging, showing several patchy areas of high-intensity signal in the right occipital lobe, in a 58-year-old woman with fatal posterior circulation stroke with persistent hiccups, sinus arrest, and post-hiccup syncope. Post-hiccup syncope occurred after a hiccup episode of 5 to 10 seconds. The pathogenesis of post-hiccup syncope was considered similar to that of cough syncope: when bouts of either coughing or hiccups occur, the rise in intrathoracic pressure acutely lowers venous return and cardiac output, leading to a decrease in cerebral perfusion and loss of consciousness. (Source: Zhang N, Liang H, Wang X, Wang H. Fatal posterior circulation stroke with persistent hiccups, sinus arrest and post-hiccup syncope: a case report. Medicine (Baltimore) 2023;102(7):e33053. Creative Commons Attribution 4.0 [CC BY] license, creativecommons.org/licenses/by/4.0.)

Diffusion-weighted imaging, showing a high-intensity signal involving the left middle cerebellar peduncle, in a 58-year-old woman with fatal posterior circulation stroke with persistent hiccups, sinus arrest, and post-hiccup syncope. Post-hiccup syncope occurred after a hiccup episode of 5 to 10 seconds. The pathogenesis of post-hiccup syncope was considered similar to that of cough syncope: when bouts of either coughing or hiccups occur, the rise in intrathoracic pressure acutely lowers venous return and cardiac output, leading to a decrease in cerebral perfusion and loss of consciousness. (Source: Zhang N, Liang H, Wang X, Wang H. Fatal posterior circulation stroke with persistent hiccups, sinus arrest and post-hiccup syncope: a case report. Medicine (Baltimore) 2023;102(7):e33053. Creative Commons Attribution 4.0 [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Cooperrider J, Kriegler J, Yunus S, Wilson R. A survey-based study examining differences in perception of postural orthostatic tachycardia syndrome between patients and primary care physicians. Cureus 2022;14[10]:e30167. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing high-uptake lesions with osteolytic bone destruction of a vertebral body and the ilium (arrows). Transverse image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing a lung nodule (arrow). Transverse image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing multiple high-uptake lesions in the liver. Frontal image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

18F-FDG PET/CT for metastatic paraganglioma, showing multiple high-uptake lesions in the liver. Transverse image. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Sagittal MRI shows an approximately circular lesion of high signal intensity on T2-weighted imaging (4.9cm×3.8cm) in the right anterior wall of the bladder. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

The size of metastases in the skull did not significantly change with two courses (far left), four courses (left center), and six courses of chemotherapy (right center), and 6-month follow-up (far right). (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

The size of metastases in the liver did not significantly change with two courses (far left), four courses (left center), and six courses of chemotherapy (right center), and 6-month follow-up (far right). (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

The size of metastases in the lung did not significantly change with two courses (far left), four courses (left center), and six courses of chemotherapy (right center), and 6-month follow-up (far right). (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paraganglioma, showing high-uptake localizations with osteolytic bone destruction of right parietal skull bone. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paraganglioma, showing multiple high-uptake localizations in the lung. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

Results of 18F-DOTATATE PET/CT for metastatic paraganglioma, showing multiple high-uptake localizations in the liver. (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

(H&E staining) (Source: Wang Z, Liu F, Li C, et al. Case report: octreotide plus CVD chemotherapy for the treatment of multiple metastatic paragangliomas after double resection for functional bladder paraganglioma and urothelial papilloma. Front Oncol 2023;12:1072361. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)

December 1905 advertisement for Collier's magazine's exposé of the patent medicine fraud, culminating in Samuel Hopkins Adams' 11-part series, "The Great American Fraud." (Illustration by American illustrator Edward Winsor Kemble (1861-1933), known best for illustrating the first edition of Mark Twain's Adventures of Huckleberry Finn. Source: Public Opinion, 1905;39(26):827.)

Photograph by American photographer Paul Thompson (1878-1940). (Source: Film Fun, May 1922. Public domain.)

The Death figure holds a bottle of wood alcohol in its right hand while leaning on its scythe on the left arm. In the background, there is a graveyard filled with burials, with mounded hummocks of earth capped by named cross-shaped grave markers. Death's scythe has cut some grass (presumably to ease grave digging) and on the grass are the words "30 cases of blindness" and "100 deaths." (Source: The News Letter. New York: National Committee for the Prevention of Blindness, 1920.)

(Source: Wikimedia Commons. Anonymous. This Treatise on the Diseases of Women is Dedicated to the Women of the World. c1904.)

Enlarged detail. To the left of the sign for "Lydia Blinkham's on draught - October brew" (on the right end of the second shelf) is a bottle of wood alcohol (methanol). It is unclear if Pinkham used some methanol in "Lydia E. Pinkham's Vegetable Compound" as the recipe evolved, but a similar patent medicine of the era, Lash’s Bitters, contained both methanol and lead (White WA III. Just What the Doctor Ordered: Biochemical Analysis of Historical Medicines from Downtown Tucson, Arizona. Intl J Hist Archaeol 2021;25:515-43). (Source: Puck (magazine) 1906;59(1520), April 18. Courtesy of the U.S. Food and Drug Administration. Public domain. Edited by Douglas J Lanska.)

Lydia Pinkham (1819-1883) was born into a prominent Quaker family in Lynn, Massachusetts. The economic recession of the 1870s forced Lydia to be enterprising, and she and her family made and marketed an herbal-alcoholic "women's tonic" for menstrual and menopausal problems. This appealed to those who sought an alternative to the "heroic" medicines of the era with their calomel (mercury-based) medicines, and the clinical focus on purging, blistering, and bleeding. With mass marketing beginning in 1876, "Lydia E. Pinkham's Vegetable Compound" became one of the best-known patent medicines of the 19th century. The principal ingredient of Lydia Pinkham Vegetable Compound was 18% alcohol, with some herbs thrown in for good measure (White WA III. Just What the Doctor Ordered: Biochemical Analysis of Historical Medicines from Downtown Tucson, Arizona. Intl J Hist Archaeol 2021;25:515-43). (Source: Puck (magazine) 1906;59(1520), April 18. Courtesy of the U.S. Food and Drug Administration. Public domain.)

Enlarged detail. This cartoon heralded the 1905 exposé of the nostrum menace, “The Great American Fraud” by American journalist and muckraker Samuel Hopkins Adams (1871-1958). A skeletal Death figure in the nasal cavity is controlling a tube from a barrel in the left orbital socket labeled "CHEAP POISONOUS ALCOHOL"--an indicator of methanol adulteration of substitution for ethanol. The tube from the right orbital socket is labeled "LAUDANUM"--ie, tincture of opium. (Source: Courtesy of the U.S. Food and Drug Administration. Public domain.)

(Public domain.)

Photograph from 1900. Geddes became the British Ambassador to the United States. (Source: U.S. Library of Congress Prints and Photographs Division, Washington, DC. Public domain.)

Comparative photograph showing the mandible of a child (A), the mandible of an adult woman (B), and the mandible of a 50-year-old acromegalic woman after 25 years of disease. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Picture shows the shape of the condyles and the asymmetry of the bone. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Lateral view of the mandible of a 50-year-old woman after 25 years of progressive disease. Photograph of dissection to show the position occupied by the mandible and its relation to the tongue. The photograph was taken before any of the deeper structures were disturbed. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Interior view of the skull base of a 50-year-old woman after 25 years of progressive disease. The tentorium cerebelli has been removed. The rest of the dura mater remains in situ to show the bowl-shaped pituitary fossa and the anteroposterior reduction in the size of the foramen magnum. The base of the skull is remarkable for the great size of the pituitary fossa, which measures 31 mm in its anteroposterior diameter and 39 mm in its transverse diameter and is 26 mm in depth. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Lateral view of the appearance of the skull (norma lateralis) of a 50-year-old woman after 25 years of progressive disease. The mandible is in the position of greatest possible "closure." (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Anterior view of the appearance of the skull (norma facialis) of a 50-year-old woman after 25 years of progressive disease. The upper three cervical vertebrae, which are ankylosed together and to the skull, are seen through the buccal gape. (Gibson case “MC” and Geddes case “EAS 07.") (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Patient, 50 years of age. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Patient, 49 years of age. There has been continued progression of facial changes since her photograph at the age of 42, and the right esotropia (divergent squint) is worse. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Geddes AC. Report upon an acromegalic skeleton. J Anat Physiol 1911;45[Pt 3]:256-92. Public domain.)

Patient, 42 years of age. Compared to her photograph at the age of 26, there has been significant progression of facial changes. The right eye became blind in the 15th year of disease (age 40), and a right esotropia (divergent squint) is apparent. There are numerous acneiform lesions on the face. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Gibson GA. Acromegaly. Edinburgh Med J 1899;6[6]:505-21. Public domain.)

Patient, 42 years of age. Compared to her photograph at the age of 26, there has been significant progression of facial changes. The right eye became blind in the 15th year of disease (age 40), and a right esotropia (divergent squint) is apparent. There are numerous acneiform lesions on the face. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Gibson GA. Acromegaly. Edinburgh Med J 1899;6[6]:505-21. Public domain.)

Patient, 42 years of age. Compared to her photograph at the age of 26, there has been significant progression of facial changes. The right eye became blind in the 15th year of disease (age 40), and a right esotropia (divergent squint) is apparent. There are numerous acneiform lesions on the face. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Gibson GA. Acromegaly. Edinburgh Med J 1899;6[6]:505-21. Public domain.)

Patient, 42 years of age. Compared to her photograph at the age of 26, there has been significant progression of facial changes. The right eye became blind in the 15th year of disease (age 40), and a right esotropia (divergent squint) is apparent. There are numerous acneiform lesions on the face. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Gibson GA. Acromegaly. Edinburgh Med J 1899;6[6]:505-21. Public domain.)

Patient, 42 years of age. Compared to her photograph at the age of 26, there has been significant progression of facial changes. The right eye became blind in the 15th year of disease (age 40), and a right esotropia (divergent squint) is apparent. There are numerous acneiform lesions on the face. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Gibson GA. Acromegaly. Edinburgh Med J 1899;6[6]:505-21. Public domain.)

Patient, 26 years of age. Compared with the photograph from 1 year earlier, there is a marked change in appearance: the lips are thicker, the nose and ears are larger, and the hair is coarser. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Gibson GA. Acromegaly. Edinburgh Med J 1899;6[6]:505-21. Public domain.)

Patient, 25 years of age. (Gibson case “MC” and Geddes case “EAS 07.”) (Source: Gibson GA. Acromegaly. Edinburgh Med J 1899;6[6]:505-21. Public domain.)

(Source: Jailani M, Barbarawi M, Tigadi S. Post total thyroidectomy deglutition syncope. Cureus 2022;14[12]:e32836. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

(Source: Jailani M, Barbarawi M, Tigadi S. Post total thyroidectomy deglutition syncope. Cureus 2022;14[12]:e32836. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0.)

Follow up at 3 months in a 27-year-old woman with granulomatous cheilitis. (Source: Tummidi S, Nagendran P, Anthony ML, Ramani RJ, Shankaralingappa A, Gopinath H. Granulomatous cheilitis of Miescher: a rare entity. BMC Womens Health 2023;23[1]:118. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Follow up at 1 month in a 27-year-old woman with granulomatous cheilitis. (Source: Tummidi S, Nagendran P, Anthony ML, Ramani RJ, Shankaralingappa A, Gopinath H. Granulomatous cheilitis of Miescher: a rare entity. BMC Womens Health 2023;23[1]:118. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Photomicroscopy of a biopsy from a 27-year-old woman who presented with a 3-month history of unrelenting upper lip swelling. The noncaseating granuloma is comprised of epithelioid cells, with a sprinkling of lymphocytes, histocytes, and multinucleated giant cells (red arrow) (H&E x 40). (Source: Tummidi S, Nagendran P, Anthony ML, Ramani RJ, Shankaralingappa A, Gopinath H. Granulomatous cheilitis of Miescher: a rare entity. BMC Womens Health 2023;23[1]:118. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Photomicroscopy of a biopsy from a 27-year-old woman who presented with a 3-month history of unrelenting upper lip swelling. The noncaseating granuloma is comprised of epithelioid cells, with a sprinkling of lymphocytes, histocytes, and multinucleated giant cells (red arrow) (H&E x 40). (Source: Tummidi S, Nagendran P, Anthony ML, Ramani RJ, Shankaralingappa A, Gopinath H. Granulomatous cheilitis of Miescher: a rare entity. BMC Womens Health 2023;23[1]:118. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Photomicroscopy of a biopsy from a 27-year-old woman who presented with a 3-month history of unrelenting upper lip swelling. A few dilated lymphatics (green arrow) are seen adjacent to the granuloma along with mild perivascular lymphoplasmacytic cuffing (H&E x 40). The noncaseating granuloma is comprised of epithelioid cells, with a sprinkling of lymphocytes, histocytes (orange arrow), and multinucleated giant cells. (Source: Tummidi S, Nagendran P, Anthony ML, Ramani RJ, Shankaralingappa A, Gopinath H. Granulomatous cheilitis of Miescher: a rare entity. BMC Womens Health 2023;23[1]:118. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Photomicroscopy of a biopsy from a 27-year-old woman who presented with a 3-month history of unrelenting upper lip swelling. The biopsy shows mucosal lining with parakeratotic stratified squamous epithelium. Mid dermis with presence of noncaseating granuloma (H&E ×10). (Source: Tummidi S, Nagendran P, Anthony ML, Ramani RJ, Shankaralingappa A, Gopinath H. Granulomatous cheilitis of Miescher: a rare entity. BMC Womens Health 2023;23[1]:118. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Non-tender diffuse swollen and firm upper lip and perioral area with areas of scaling in a 27-year-old woman who presented with a 3-month history of this problem. Biopsy from the lesion was consistent with granulomatous cheilitis. (Source: Tummidi S, Nagendran P, Anthony ML, Ramani RJ, Shankaralingappa A, Gopinath H. Granulomatous cheilitis of Miescher: a rare entity. BMC Womens Health 2023;23[1]:118. Creative Commons Attribution 4.0 International [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Photograph shows the fissured tongue in a 38-year-old woman referred by her dentist for evaluation of recurrent swelling of the lower lip along with left hemifacial palsy. She was diagnosed with Melkersson-Rosenthal syndrome based on its three clinical features: recurrent facial palsy, orofacial swelling, and fissured tongue. (Source: Aoun G, Skandri N, Ghattas H, Maksoud C. Melkersson-Rosenthal syndrome in a 38-year-old female patient: a rare case with complete triad. Cureus 2022;14[7]:e27427. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

Photograph shows swelling of the lower lip in a 38-year-old woman referred by her dentist for evaluation of recurrent swelling of the lower lip along with left hemifacial palsy. She was diagnosed with Melkersson-Rosenthal syndrome based on its three clinical features: recurrent facial palsy, orofacial swelling, and fissured tongue. (Source: Aoun G, Skandri N, Ghattas H, Maksoud C. Melkersson-Rosenthal syndrome in a 38-year-old female patient: a rare case with complete triad. Cureus 2022;14[7]:e27427. Creative Commons Attribution [CC-BY 4.0] license, creativecommons.org/licenses/by/4.0. The image has been cropped from the original.)

(Source: Bert P. La pression barométrique: recherches de physiologie expérimentale. Paris: G. Masson, 1878. Public domain.)

Drawing c1873. Divers were apparently recoving the bodies and other remains from the wreck of the Northfleet, which sank on January 22nd. (Source: The Illustrated London News on February 8, 1873. Public domain.)

Augustus Siebe (1788-1872) diving helmet invented in 1819 for an "open dress" form of diving to provide greater mobility to the diver. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

The diving apparatus of Kleingert, constructed in 1798. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

c1860. (Source: The Pictorial Gallery of Arts, London Printing and Publishing, 1860.)

An improved version of Halley's diving bell by Edinburgh confectioner and amateur engineer in 1775. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Mezzotint on moderately thick, slightly textured, cream, laid paper by John Faber Jr. (1684-1756). (Source: Yale Center for British Art. Creative Commons CC0 1.0 Universal Public Domain Dedication.)

Drawing circa 1717. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Cité de la Mer, a maritime museum in Cherbourg, France. (Source: Photograph by Ji-Elle in April 2008. Public domain.)

(Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(von Schrötter) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(Siebe, Gorman and Co.) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(von Schrötter) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Low-power photomicrograph. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(1) Normal cat kidney. (2) Cat kidney after decompression from 8 atmospheres in 5 seconds. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

High-power photomicrograph. The hepatocytes are honeycombed with bubbles. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Low-power photomicrograph. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(1) Normal cat liver. (2) Cat liver after decompression from 8 atmospheres in 5 seconds. Bubbles have formed in the fat within the hepatocytes and also are present within the lumens of capillaries. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Oxygen poisoning damage to the lung, showing an alveolus of the lung (high power), exudation of leucocytes, and congestion of capillaries (high power). (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Oxygen poisoning damage to the lung, showing exudation in a bronchiolar tube and the alveoli of the lung. (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

A fish brought up from a considerable depth with a distended swim bladder prolapsed, everted, and projecting from its mouth (after Regnard). (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(von Schrötter) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Ascending and descending degeneration is shown in the sections above and below these levels (Boycott and Damant). (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(Boycott and Damant) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(Boycott and Damant) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(von Schrötter) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

(Heller, Mager, and von Schrötter) (Source: Hill L. Caisson sickness and the physiology of work in compressed air. London: Edward Arnold, 1912. Public domain.)

Photo c1880. (Source: Wikimedia Commons. Public domain.)

Photo taken 1948. (Souce: Creative Commons Attribution-Share Alike 3.0 Unported [CC BY-SA 3.0] license, creativecommons.org/licenses/by-sa/3.0/deed.en.)

Photo c1930. (Source: Wikimedia Commons. Public domain.)

Photo taken 1942. (Source: US Army. Public domain.)

(Source: Wikimedia Commons. Public domain.)

A sample dive profile of a 25-minute dive to 60 meters breathing Trimix (oxygen, helium, and nitrogen), showing decompression strops from 39 meters to 3 meters on Nitrox (nitrogen and oxygen) and Oxygen. (Source: Illustration by Mark Murphy June 16, 2008. Public domain.)

Divers decompressing at the 6m stop on a decompression trapeze at 12 Mile Bank, south of Cape Agulhas, near Struisbaai in the Western Cape province of South Africa. (Source: Photography by Peter Southwood on April 9, 2001. Creative Commons Attribution-Share Alike 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by-sa/4.0/deed.en.)

Note the periorbital ecchymoses and the bilateral subconjunctival hemorrhages. (Source: Wikimedia Commons user:prilfish, 2003. Creative Commons Attribution 2.0 Generic [CC BY] license, creativecommons.org/licenses/by/2.0/deed.en.)

Coronal section of cerebral MRI FLAIR sequence showing hyperintense signal change of the mammary bodies in a 66-year-old man with Wernicke encephalopathy complicating prolonged parenteral nutrition. (Source: Slim S, Ayed K, Triki W, et al. Gayet-Wernicke's encephalopathy complicating prolonged parenteral nutrition in patient treated for colonic cancer - a case report. BMC Nutr 2022;8[1]:83. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4.0. Image cropped from original.)

In this 48-year-old man with the stuttering progression of neurologic deficits over several months, the follow-up FLAIR sequence showed pontine hyperintensities (thick red arrows). (Source: Olowoporoku IG, Digala LP, Attele DP. Central pontine myelinolysis: a case report of persistent hyperglycemia with normal serum sodium. Cureus 2022;14[9]:e29470. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

In this 48-year-old man with the stuttering progression of neurologic deficits over several months, the follow-up T2-weighted image showed worsening pontine hyperintensities (thin red arrows). (Source: Olowoporoku IG, Digala LP, Attele DP. Central pontine myelinolysis: a case report of persistent hyperglycemia with normal serum sodium. Cureus 2022;14[9]:e29470. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

In this 48-year-old man with the stuttering progression of neurologic deficits over several months, the initial T2-weighted MR imaging showed pontine hyperintensities (thin red arrows). (Source: Olowoporoku IG, Digala LP, Attele DP. Central pontine myelinolysis: a case report of persistent hyperglycemia with normal serum sodium. Cureus 2022;14[9]:e29470. Creative Commons Attribution license [CC BY], creativecommons.org/licenses/by/4.0.)

In this 44-year-old diabetic man with osmotic demyelination syndrome, axial T2-weighted MR images show bilateral hyperintensity in the pons and cerebellum. (Source: Shrestha S, Kharel S, Gautam S, et al. Pontine and bilateral cerebellar lesion in osmotic demyelination syndrome associated with uncontrolled type II diabetes mellitus: a case report. Ann Med Surg [Lond] 2023;85[3]:477-80. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

In a 34-year-old female with longstanding uncontrolled diabetes mellitus who presented with quadriparesis and dysphagia, laboratory investigations showed high HbA1c (12.3%), high blood glucose (278 mg/dL), increased serum osmolality, and normal corrected sodium (138 mg/dL). This sagittal T1-weighted image shows a mildly hypointense lesion in the central pons (black circle). (Source: Mir WA, Shrestha DB, Aryal BB, Reddy VK, Yadullahi MA. Central pontine myelinolysis secondary to hyperglycemia in a young patient. Cureus 2021;13[10]:e18495. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

In a 34-year-old female with longstanding uncontrolled diabetes mellitus who presented with quadriparesis and dysphagia, laboratory investigations showed high HbA1c (12.3%), high blood glucose (278 mg/dL), increased serum osmolality, and normal corrected sodium (138 mg/dL). This axial FLAIR image shows marked hyperintensity over the pons (black circle). (Source: Mir WA, Shrestha DB, Aryal BB, Reddy VK, Yadullahi MA. Central pontine myelinolysis secondary to hyperglycemia in a young patient. Cureus 2021;13[10]:e18495. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

In a 34-year-old female with longstanding uncontrolled diabetes mellitus who presented with quadriparesis and dysphagia, laboratory investigations showed high HbA1c (12.3%), high blood glucose (278 mg/dL), increased serum osmolality, and normal corrected sodium (138 mg/dL). This axial T2-weighted MRI shows symmetric hyperintense lesions in the pons (black circles). (Source: Mir WA, Shrestha DB, Aryal BB, Reddy VK, Yadullahi MA. Central pontine myelinolysis secondary to hyperglycemia in a young patient. Cureus 2021;13[10]:e18495. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

T2-weighted MRI in a 41-year-old woman who presented with acute parkinsonism following slow correction of hyponatremia resulting from repeated vomiting, and whose initial MRI was consistent with extrapontine myelinolysis. MRI after two months showing marked improvement, mainly in the putamena (long black arrow). (Source: Sajith J, Ditchfield A, Katifi HA. Extrapontine myelinolysis presenting as acute parkinsonism. BMC Neurol 2006;6:33. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

T2-weighted MRI in a 41-year-old woman who presented with acute parkinsonism following slow correction of hyponatremia resulting from repeated vomiting. MRI of the pons showed no abnormality. (Source: Sajith J, Ditchfield A, Katifi HA. Extrapontine myelinolysis presenting as acute parkinsonism. BMC Neurol 2006;6:33. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

T2-weighted FLAIR in a 41-year-old woman who presented with acute parkinsonism following slow correction of hyponatremia resulting from repeated vomiting. Images showed bilaterally symmetrical hyperintensities in the caudate nuclei (small, thin, black arrow) and putamena (long black arrow), with sparing of globi pallidi (broad black arrow), consistent with extrapontine myelinolysis. (Source: Sajith J, Ditchfield A, Katifi HA. Extrapontine myelinolysis presenting as acute parkinsonism. BMC Neurol 2006;6:33. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

T2-weighted MRI in a 41-year-old woman who presented with acute parkinsonism following slow correction of hyponatremia resulting from repeated vomiting. MRI showed symmetrical hyperintensities in caudate nuclei (small, thin, black arrow) and putamena (long black arrow), with sparing of the globi pallidi (broad black arrow), consistent with extrapontine myelinolysis. (Source: Sajith J, Ditchfield A, Katifi HA. Extrapontine myelinolysis presenting as acute parkinsonism. BMC Neurol 2006;6:33. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

MRI in a 45-year-old alcoholic woman with a recent hospitalization for Wernicke encephalopathy who presented with left hemiparesis and was initially suspected to have had a stroke. (a) Axial T2-weighted image demonstrates high T2-signal intensity in the upper pons, resembling a pig’s snout (the so-called “piglet sign”). (b) The same axial T2-weighted image with the area of edema of the pons is highlighted in green. The transverse pontine fibers (pontocerebellar fibers and median raphe) are most affected and there is sparing of the peripheral (ventrolateral longitudinal) fibers and corticospinal tracts, producing the pig’s snout appearance. The edema involves the right corticospinal tracts (blue arrow), which explains the patient's left-sided hemiparesis. (c and d) DWI and apparent diffusion coefficient (ADC) map corresponding to the restricted diffusion in the pons. (e) Sagittal FLAIR image demonstrates increased FLAIR signal in the pons. (Source: Kusel K, Azzam O, Youssef A, Prentice D. Alcoholic pontine myelinolysis: beware the stroke mimic. BJR Case Rep 2021;7(4):20210005. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

CT perfusion images in a 45-year-old alcoholic woman with a recent hospitalization for Wernicke encephalopathy who presented with left hemiparesis and was initially suspected to have had a stroke. CT perfusion images at the level of the pons demonstrate increased blood flow (top right, yellow arrow), reduced mean transit time (bottom left, red arrow), and reduced time-to-maximum (bottom right, orange arrow) in the upper pons. (Source: Kusel K, Azzam O, Youssef A, Prentice D. Alcoholic pontine myelinolysis: beware the stroke mimic. BJR Case Rep 2021;7(4):20210005. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

CT image in a 45-year-old alcoholic woman with a recent hospitalization for Wernicke encephalopathy who presented with left hemiparesis and was initially suspected to have had a stroke. The axial, non-contrast CT was unrevealing, as in this image at the level of the pons. (Source: Kusel K, Azzam O, Youssef A, Prentice D. Alcoholic pontine myelinolysis: beware the stroke mimic. BJR Case Rep 2021;7(4):20210005. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

(100 mmol/L). This 44-year-old man was treated with sodium supplementation with 3% hypertonic saline and water restriction and developed altered mental status with agitation, limb rigidity, bradykinesia, and dystonia on hospital day 2. Diffusion-weighted imaging (DWI) on hospital day 12 showed that the previous lesions of the caudate nucleus and putamen had become more conspicuous, and a new high intensity lesion was then evident, involving the central pons and consistent with central pontine myelinolysis. (Source: Lee C, Ko C. Temporal brain MRI changes from extrapontine myelinolysis to central pontine myelinolysis: a case report. Cureus 2021;13[11]:e19318. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

(100 mmol/L) This 44-year-old man was treated with sodium supplementation with 3% hypertonic saline and water restriction and developed altered mental status with agitation, limb rigidity, bradykinesia, and dystonia on hospital day 2. The initial MRI at that time showed symmetrical high-intensity lesions at the head of caudate nucleus and putamen. (Source: Lee C, Ko C. Temporal brain MRI changes from extrapontine myelinolysis to central pontine myelinolysis: a case report. Cureus 2021;13[11]:e19318. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

(100 mmol/L) This 44-year-old man was treated with sodium supplementation with 3% hypertonic saline and water restriction and developed altered mental status with agitation, limb rigidity, bradykinesia, and dystonia on hospital day 2. The initial MRI at that time showed no significant abnormalities on FLAIR (A) and T2-weighted images (B). (Source: Lee C, Ko C. Temporal brain MRI changes from extrapontine myelinolysis to central pontine myelinolysis: a case report. Cureus 2021;13[11]:e19318. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

Follow-up MRI performed at 20 months of age showed symmetric high-signal-intensity changes in the superior cerebellar peduncle, lateral pons, thalami, and posterior limb of internal capsule on T2-weighted images (T2WI). (Source: Kobayashi S, Mizuno N, Yokoi K, Mori T, Sohara E, Uchida S. Congenital nephrogenic diabetes insipidus presenting as osmotic demyelination syndrome in infancy: a case report. Medicine (Baltimore) 2022;101(3):e28552. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

Initial MRI on the third hospital day showed multifocal, symmetric lesions within the superior cerebellar peduncle, lateral pons, thalami, and posterior limb of internal capsule on T2-weighted images (T2WI) and diffusion-weighted imaging (DWI). (Source: Kobayashi S, Mizuno N, Yokoi K, Mori T, Sohara E, Uchida S. Congenital nephrogenic diabetes insipidus presenting as osmotic demyelination syndrome in infancy: a case report. Medicine (Baltimore) 2022;101(3):e28552. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/4.0.)

FLAIR MRI in a 51-year-old man who developed osmotic demyelination syndrome due to rhabdomyolysis and hyperosmolar hyperglycemic syndrome following cardiogenic shock. MRI FLAIR images on day 57 revealed symmetrical hyperintensity in the thalamus (arrow). (Source: Katano K, Fuse N, Asano Y, et al. Osmotic demyelination syndrome due to rhabdomyolysis and hyperosmolar hyperglycemic syndrome following cardiogenic shock. Case Rep Crit Care 2021;2021:8083731. Copyright © 2021 Kosuke Katano, et al. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

FLAIR MRI in a 51-year-old man on day 57 after cardiogenic shock revealed symmetrical hyperintensity in the hippocampus and hypothalamus (arrow). (Source: Katano K, Fuse N, Asano Y, et al. Osmotic demyelination syndrome due to rhabdomyolysis and hyperosmolar hyperglycemic syndrome following cardiogenic shock. Case Rep Crit Care 2021;2021:8083731. Copyright © 2021 Kosuke Katano, et al. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

FLAIR MRI in a 51-year-old man on day 57 after cardiogenic shock revealed symmetrical hyperintensity in the pons and cerebellar hemispheres (arrow). (Source: Katano K, Fuse N, Asano Y, et al. Osmotic demyelination syndrome due to rhabdomyolysis and hyperosmolar hyperglycemic syndrome following cardiogenic shock. Case Rep Crit Care 2021;2021:8083731. Copyright © 2021 Kosuke Katano, et al. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

DWI MRI in a 51-year-old man on day 16 after cardiogenic shock revealed no changes in the findings except loss of hyperintensity on diffusion-weighted imaging (DWI). (Source: Katano K, Fuse N, Asano Y, et al. Osmotic demyelination syndrome due to rhabdomyolysis and hyperosmolar hyperglycemic syndrome following cardiogenic shock. Case Rep Crit Care 2021;2021:8083731. Copyright © 2021 Kosuke Katano, et al. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

FLAIR MRI in 51-year-old man on day 10 after cardiogenic shock revealed only symmetrical hyperintensity in the putamen and posterior limb of the internal capsule (arrow) on FLAIR images. (Source: Katano K, Fuse N, Asano Y, et al. Osmotic demyelination syndrome due to rhabdomyolysis and hyperosmolar hyperglycemic syndrome following cardiogenic shock. Case Rep Crit Care 2021;2021:8083731. Copyright © 2021 Kosuke Katano, et al. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

DWI MRI in 51-year-old man on day 10 after cardiogenic shock revealed symmetrical hyperintensity in the putamen and posterior limb of the internal capsule (arrow) on diffusion-weighted imaging (DWI). (Source: Katano K, Fuse N, Asano Y, et al. Osmotic demyelination syndrome due to rhabdomyolysis and hyperosmolar hyperglycemic syndrome following cardiogenic shock. Case Rep Crit Care 2021;2021:8083731. Copyright © 2021 Kosuke Katano, et al. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)

Axial T1-weighted MRI demonstrated symmetric low signal in the central pons (A, E). Axial T2-weighted MRI demonstrated a symmetric high signal in the central pons (B, F). T2 FLAIR images demonstrated a symmetric high signal in the central pons (C, G). Diffusion-weighted imaging (DWI) showed no diffusion restriction in the central pons (D, H). (Source: Jin X, Wang Y. Case report: osmotic demyelination syndrome after transcatheter aortic valve replacement: case report and review of current literature. Front Med (Lausanne) 2022;9:915981. Creative Commons Attribution license [CC BY], https://creativecommons.org/licenses/by/2.0.)