Neuropharmacology & Neurotherapeutics

After surgical tumor debulking and dorsal fusion from T5 to T9, fluoroscopy confirms correct placement of the rods and the screw tips. (Contributed by Kristine Ann Blackham MD.)

Selective angiography of the right T7 segmental artery after embolization with 250-micron particles depicts a markedly reduced tumor blush from a successful embolization. (Contributed by Kristine Ann Blackham MD.)

Selective angiography of the right T7 segmental artery (dashed arrow) reveals a large tumor blush at the expected location of vertebral bodies T7/8 (straight arrows). Note filling of the segmental artery of T6 via collaterals. (Contributed by Kristine Ann Blackham MD.)

(A) Sagittal T1-weighted, (B) T2-weighted, and (C) post-contrast T1 Dixon water-only MRI show near replacement of the vertebral body T7 by a tumor mass (white straight arrows), best seen as fat extinction in (A). Intraspinal epidural extension is depicted (straight black arrows) as well as cord displacement. (D) Axial T2-weighted MRI at the level of T7 shows extensive extraosseous soft tissue components on both sides (dashed white arrows) and substantial intraspinal epidural tumor extension (dashed black arrows). The cord is displaced backward and slightly to the left. Only very little CSF is visible dorsal to the cord. (Contributed by Kristine Ann Blackham MD.)

After injection of the mixture of iodine-based contrast agent, local anesthetic, and glucocorticoid, a final axial CT shows the contrast agent around the nerve sheath (white arrow) as well as in the epidural space (black arrows). The distribution of the local anesthetic and the glucocorticoid can be assumed to be identical to the contrast agent. (Contributed by Kristine Ann Blackham MD.)

Axial noncontrast CT scan (right side of the patient is at the top of the image). By using guidance software, the intended course of the infiltration needle from the skin (X) to just next to the L4 spinal nerve (arrowhead) is drawn. (Contributed by Kristine Ann Blackham MD.)

Another axial CT obtained after insertion of the needle confirms correct position of the needle tip just next to the right L4 neuroforamen (straight arrow). The needle entered the skin exactly at the intended location (dashed arrow). This is facilitated by a focus of red light pointing at the planned puncture site on the patient’s skin that also provides angle information. (Contributed by Kristine Ann Blackham MD.)

T2-weighted axial MRI of the lumbar spine shows the foraminal and proximal extraforaminal course of the right L4 spinal nerve (straight arrow). The foraminal protrusion of disc material is shown (dashed arrows). Compared to the contralateral side, the right L4 spinal nerve has contact to the disc material. (Contributed by Kristine Ann Blackham MD.)

T2-weighted sagittal MRI of the lumbar spine shows the right L4 spinal nerve within the corresponding neuroforamen (straight arrow). The neuroforamen is partially obstructed by a hypointense mass inferiorly (dashed arrow), corresponding to disc material. The amount of hyperintense fat within the neuroforamen is reduced, and the configuration of the L4 spinal nerve suggests deformation. (Contributed by Kristine Ann Blackham MD.)

Left image: a lateral digital subtraction angiography image in the arterial phase of contrast injection in the right common carotid artery shows ectasia of the anterior falcine artery arising from the ophthalmic artery (arrow), which gives rise to a high-flow arteriovenous shunt as it connects directly to the superior sagittal sinus (arrowhead). Early venous drainage, which is opacification of the veins during the arterial phase of contrast administration, is the hallmark of an arteriovenous shunt. Right image: post-procedure, the shunt is gone, and there is no early venous drainage. (Contributed by Kristine Ann Blackham MD.)

Anteroposterior (left) and lateral (right) digital subtraction angiography images obtained by contrast injection in the right external carotid artery show contrast opacification of the middle meningeal artery, which no longer has an arteriovenous communication with the superior sagittal sinus (arrow). In fact, because the high flow shunt is no longer present, there was some reflux of contrast into the right common carotid artery, and the capillary phase of the intracranial circulation is visualized. The coil mass and liquid embolic material are subtracted but still visible on close inspection (asterisk). (Contributed by Kristine Ann Blackham MD.)

Following transvenous coiling of the superior sagittal sinus and distal liquid embolic embolization via the middle meningeal artery, the lateral unsubtracted view of the skull shows the large radiopaque (black) coil mass in the superior sagittal sinus at the level of the fistula point. The liquid embolic material is also black and is dispersed within the coil interstices. (Contributed by Kristine Ann Blackham MD.)

Anteroposterior (AP) and lateral views of the left external carotid artery injection show hypertrophy of several branches of the middle meningeal artery (AP image 8 of 22, 0 sec). The enlarged middle meningeal artery has a fistulous connection with the superior sagittal sinus. This results in early and abnormal contrast opacification of the superior sagittal sinus (AP image 13 of 22, 2 sec, and lateral image 12 of 22, 7 sec). The fistulous drainage continues into the right transverse and sigmoid sinuses and right internal jugular vein (AP image 20 of 22, 3 sec). This “arterialization” of the sinuses renders them incapable of receiving the normal venous drainage of the brain. (Contributed by Dr. Kristine Ann Blackham.)

Anteroposterior (AP) and lateral views of the right external carotid artery injection show a hypertrophied middle meningeal artery (AP image 10 of 21, 1 sec). The enlarged middle meningeal artery has a fistulous connection with the superior sagittal sinus, which results in early and abnormal contrast opacification of the superior sagittal sinus (AP image 12 of 21, 1 sec, and lateral image 13 of 21, 7 sec). The fistulous drainage continues into the right transverse and sigmoid sinuses and right internal jugular vein (AP image 21 of 21, 3 sec). This “arterialization” of the sinuses renders them incapable of receiving the normal venous drainage of the brain. (Contributed by Dr. Kristine Ann Blackham.)

Anteroposterior (AP) and lateral views of the left internal carotid artery injection show a normal appearance of the left middle and anterior cerebral artery (AP image 8 of 23, 0 sec). There is early and abnormal contrast opacification of the superior sagittal sinus, indicating a fistulous shunt (AP image 12 of 23, 1 sec, and lateral image 10 of 23, 7 sec). The feeders are from the anterior falcine artery (via the left ophthalmic artery) and the distal left pericallosal artery (via the left ACA). In the normal venous phase, none of the normal dural venous sinuses are opacified; all of the venous drainage of the brain is via collateral vessels (AP image 24 of 23, 4 sec and lateral image 24 of 23, 10 sec). (Contributed by Dr. Kristine Ann Blackham.)

Anteroposterior (AP) and lateral views of the right common carotid artery injection show a normal appearance of the right middle and anterior cerebral artery and flash opacification of the left ACA (AP image 15 of 26, 2 sec). There is early and abnormal contrast opacification of the superior sagittal sinus, indicating a fistulous shunt (AP image 15 of 26, 2 sec, and lateral image 10 of 26, 8 sec). The feeders are from the anterior falcine artery (via the right ophthalmic artery) and the distal left pericallosal artery (via the left ACA). In the normal venous phase, none of the normal dural venous sinuses are opacified; all of the venous drainage of the brain is via collateral vessels (AP image 27 of 26, 5 sec, and lateral image 28 of 26, 12 sec). (Contributed by Dr. Kristine Ann Blackham.)

Anteroposterior (left) and lateral (right) digital subtraction angiography images obtained by contrast injection in the right external carotid artery show ectasia of the middle meningeal artery (arrow), which connects directly to the superior sagittal sinus through a fistulous point (asterisk), resulting in a high flow arteriovenous shunt. (Contributed by Kristine Ann Blackham MD.)

Noncontrast axial CT shows hyperdense hemorrhage predominantly in the left lateral and third ventricles (arrows). There are small foci of intraparenchymal hemorrhage in the left frontal lobe, adjacent to the ventricle and anteriorly (arrowhead). The ventricles are dilated, consistent with hydrocephalus. (Contributed by Kristine Ann Blackham MD.)

Axial T2-weighted images again show intraventricular hemorrhage (asterisk) within a dilated ventricular system. There are dilated flow-voids (arrows) that represent abnormally enlarged vessels. These indicate the presence of a high flow vascular malformation. (Contributed by Kristine Ann Blackham MD.)

Anteroposterior (left) and lateral (right) angiographic views of the intracranial arteries after contrast injection into the right common carotid artery reveal improvement in the majority of vasospasms. (Contributed by Kristine Ann Blackham MD.)

Axial FLAIR (fluid attenuated inversion recovery) MRI displays the known foci of subarachnoid hemorrhage. No new pathology is depicted. (Contributed by Kristine Ann Blackham MD.)

Anteroposterior (left) and lateral (right) angiographic views of the intracranial arteries after contrast injection into the right common carotid artery reveal several segmental caliber reductions of the intracranial arteries (black arrows), compatible with vasoconstriction. (Contributed by Kristine Ann Blackham MD.)

Axial MRI with diffusion-weighted images (DWI; b=1000 images are displayed) shows a punctate focus of diffusion restriction in the right parietal lobe (left image, dashed arrow) and small areas of diffusion restriction in the right basal ganglia (right image, straight arrows). Signal reduction in the corresponding apparent diffusion coefficient map (ADC; not displayed) confirmed these to be areas of acute infarction. However, the majority of the right middle cerebral artery territory is unaffected. (Contributed by Kristine Ann Blackham MD.)

Axial noncontrast CT of the head shows subarachnoid hemorrhage (white arrows) in bilateral supratentorial sulci. (Contributed by Kristine Ann Blackham MD.)

Anteroposterior (left) and lateral (right) views of the intracranial arteries after contrast injection into the right common carotid artery show the successful result after thrombectomy (thrombolysis in cerebral infarction scale 3). All middle cerebral artery branches are contrasted without residual filling defects and without delay compared to the anterior cerebral artery branches. (Contributed by Kristine Ann Blackham MD.)

Coronal maximum intensity projection from computed tomography angiography shows abrupt cut-off of contrast opacification in the M1 segment of the right middle cerebral artery. (Contributed by Kristine Ann Blackham MD.)

Anteroposterior (left) and lateral (right) views of the intracranial arteries after contrast injection into the right common carotid artery confirm the abrupt discontinuation of contrast filling in the M1 segment of the right middle cerebral artery, corresponding to vessel occlusion. (Contributed by Kristine Ann Blackham MD.)

Color-coded transverse perfusion maps from computed tomography perfusion of cerebral blood flow (CBF), time to drain (TTD), and time to peak (TTP) show a large territorial perfusion delay in the right middle cerebral artery territory. A color-coded map of cerebral blood volume shows reductions of cerebral blood volume in a much smaller area containing the head of the right caudate nucleus and lentiform nucleus. (Contributed by Kristine Ann Blackham MD.)

Axial CT image at the level of the suprasellar cistern depicts a hyperdense M1 segment of the right middle cerebral artery (white arrow). (Contributed by Kristine Ann Blackham MD.)

(Contributed by Dr. K K Jain.)

Nerve growth factor is released from the tissue mast cells as a result of nervous, immune, or endocrine influences and can affect the same systems. It can also function in an autocrine manner.

(Contributed by Dr. Sudhir Kothari.)

(Contributed by Dr. Sudhir Kothari.)

(Contributed by Dr. Sudhir Kothari.)

(1) Passive diffusion. Fat-soluble substances dissolve in the cell membrane and cross the barrier, eg, alcohol, nicotine, and caffeine. Water-soluble substances like penicillin have difficulty in getting through. (2) Active transport. Substances that the brain needs such as glucose and amino acids are carried across by special transport proteins. (3) Receptor-mediated transport. Molecules link up to receptors on the surface of the brain and are escorted through, eg, insulin. (Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

English physician and scientist Edward Jenner (1749-1823) was pioneer of the smallpox vaccine. Drawing by Vigneron Pierre Roch, circa 1824. (Contributed by Dr. Douglas Lanska. Public domain. Courtesy of BIU Health Medicine Collection.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

The serotonin (5-HT) system consists of a diverse group of neurons (the cell bodies of which are located in the brainstem raphe nuclei, the reticular formation, and complex axonal systems) that innervate virtually the whole central nervous system. Some of the serotonin neurons do not make synaptic contacts but, rather, terminate in a field of neurons that are influenced by the serotonin released at the terminals. Serotonin neurons are found abundantly in the limbic structures that contribute to emotional behavior and learning. The hippocampus, a component of the limbic system, is richly innervated by serotonergic, noradrenergic, and other neurotransmitter systems. There are several axonal pathways from the dorsal and median raphe 5-HT neurons to the hippocampus. Some fine axons in this pathway are distributed to the CA1 and CA3 layers of the hippocampus and are susceptible to damage by serotonin neurotoxins. In contrast to the hippocampus, serotonin innervation of the cerebellum is rather sparse. However, there is a complex and well-organized modulation of glutaminergic transmission via 5-HT receptors in the cerebellum. This interaction may play an important role in the cerebral control of movement and ataxia as shown by the efficacy of 5-HT1A antagonists in clinical studies of cerebellar ataxia. (Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

The structural formula of propofol (2,6-diisopropylphenol), C12H18O. (Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

Polish-American virologist Albert Sabin (1906-1993) developed the first effective trivalent live-attenuated (oral) poliovirus vaccine. (Contributed by Dr. Douglas Lanska. Source: Woodward T. The Armed Forces Epidemiological Board: Its First Fifty Years. Falls Church, VA: Office of the Surgeon General, Department of the Army, 1990. Public domain photograph of a U.S. Army soldier taken in the course of the person’s official duties.)

American virologist Jonas Salk (1914-1995) in 1988. Salk developed the first effective trivalent killed-virus poliovirus vaccine. (Contributed by Dr. Douglas Lanska. Courtesy of the U.S. Public Health Image Library.)

(Contributed by Dr. Sudhir Kothari.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

Steps in the ischemic cascade and site of action of neuroprotectives. (Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

Introduction of tyrosine hydroxylase gene directly into the striatum increases tyrosine hydroxylase production and, in the presence of cofactor tetrahydrobiopterin, results in endogenous dopamine synthesis and release. (Contributed by Dr. K K Jain.)

Ex vivo and in vivo techniques of gene therapy. (Reproduced from: Jain KK. Textbook of gene therapy. Toronto, Bern, Gottingen: Hogrefe and Huber, 1998.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

Chemical formula of donepezil (E-2020): C24 H29 N O3 . H Cl (Contributed by Dr. K K Jain.)

Interactions of players in clinical trials of Alzheimer disease in the United States. (Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

(Contributed by Dr. K K Jain.)

40-year-old man with progressive spastic quadriparesis for 1 year. Atlantoaxial dislocation and spinal cord compression as labeled. No history of rheumatoid arthritis in this example. (Provided by Dr. Sudhir Kothari.)