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  • Updated 06.01.2024
  • Released 06.01.2024
  • Expires For CME 06.01.2027

Multiple cranial neuropathies: intramedullary lesions

Introduction

Overview

This article discusses intramedullary cranial polyneuropathies that are supranuclear, internuclear, nuclear, fascicular, or some combination. Supranuclear cranial polyneuropathies result from bilateral disease, usually of the hemispheres, and include pseudobulbar palsy and Foix-Chavany-Marie syndrome. Cranial polyneuropathies with an internuclear component typically result from pontine lesions and include one-and-a-half syndrome and associated paralytic pontine exotropia, as well as more extensive forms with intramedullary involvement of other cranial nerves--the one-and-a-half syndrome spectrum disorders. Cranial polyneuropathies with nuclear or fascicular involvement include a variety of brainstem syndromes, such as facial colliculus syndrome, Millard-Gubler syndrome, Foville syndrome, superior cerebellar artery syndrome, anterior inferior cerebellar artery syndrome, lateral medullary syndrome, medial medullary syndrome, Avellis syndrome, and Garcin syndrome (spanning the cranial nerves on one side).

Key points

• Supranuclear cranial polyneuropathies result from bilateral disease of the rostral neuraxis, usually of the cerebral hemispheres, and include pseudobulbar palsy and Foix-Chavany-Marie syndrome.

• Cranial polyneuropathies with an internuclear component typically result from pontine lesions and include one-and-a-half syndrome and associated paralytic pontine exotropia, as well as more extensive forms with intramedullary involvement of other cranial nerves—the one-and-a-half syndrome spectrum disorders.

• Cranial polyneuropathies with nuclear or fascicular involvement include a variety of brainstem syndromes, such as facial colliculus syndrome, Millard-Gubler syndrome, superior cerebellar artery syndrome, anterior inferior cerebellar artery syndrome, lateral medullary syndrome, medial medullary syndrome, Avellis syndrome, and Garcin syndrome (spanning the cranial nerves on one side).

Historical note and terminology

Supranuclear cranial polyneuropathies. Supranuclear cranial polyneuropathies result from bilateral disease of the rostral neuraxis, usually of the cerebral hemispheres, and include pseudobulbar palsy and Foix-Chavany-Marie syndrome.

Pseudobulbar palsy. Berlin physician A Magnus reported the first case of pseudobulbar palsy in 1837 in a patient with multiple infarcts (81). In 1877, French physician and physiologist Jacques Raphaël Lépine (1840-1919) introduced the term pseudobulbar palsy (77).

French physiologist Jacques Raphaël Lépine (1840 -1919)

(Courtesy of the U.S. National Library of Medicine, Bethesda, Maryland. Public domain.)

Bilateral anterior opercular syndrome (Foix-Chavany-Marie syndrome). Bilateral anterior opercular syndrome (Foix-Chavany-Marie syndrome) was more extensively investigated by French neurologists Charles Foix (1882-1927) and Jean Alfred Émile Chavany (1892-1959) with French pediatrician Julien Marie (1899-1987) in 1926 (39).

Cranial polyneuropathies with an internuclear component. Cranial polyneuropathies with an internuclear component typically result from pontine lesions and include one-and-a-half syndrome and associated paralytic pontine exotropia, as well as more extensive forms with intramedullary involvement of other cranial nerves—the one-and-a-half syndrome spectrum disorders.

One-and-a-half syndrome. Canadian neurologist C Miller Fisher (1913-2012) provided a masterful description of one-and-a-half syndrome in 1967 (38):

In lesions of the brainstem, vascular particularly, demyelinative or neoplastic more rarely, there occasionally occurs a paralysis of eye movements in which one eye lies centrally and fails completely to move horizontally while the other eye lies in an abducted position and cannot be adducted past the midline. ... We have attributed the syndrome to a lesion in or near the pontine conjugate lateral gaze centre on one side (causing the conjugate gaze palsy) plus an internuclear ophthalmoplegia due to the interruption of the ipsilateral medial longitudinal fasciculus after it has crossed the midline from its site of origin in the contralateral vestibular nucleus (causing failure of adduction of the ipsilateral eye). ... This syndrome which we have colloquially termed the 'one and a half syndrome' because it consists of a conjugate lateral gaze palsy in one direction, plus one half of a gaze palsy in the other, provides evidence that the medial longitudinal fasciculus fibres running to the opposite ocular adductors cross to the other side caudally in the pons near their origin in the vestibular nucleus rather than running cephalad for some distance before crossing (38; page 386).

Paralytic pontine exotropia. In 1974, paralytic pontine exotropia as a sign of acute unilateral pontine gaze palsy and internuclear ophthalmoplegia was described by James A Sharpe and colleagues Michael A Rosenberg, William F Hoyt, and Robert B Daroff (121).

Cranial polyneuropathies with nuclear or fascicular involvement. Cranial polyneuropathies with nuclear or fascicular involvement include a variety of brainstem syndromes, such as facial colliculus syndrome, Millard-Gubler syndrome, superior cerebellar artery syndrome, anterior inferior cerebellar artery syndrome, lateral medullary syndrome, medial medullary syndrome, Avellis syndrome, and Garcin syndrome (spanning the cranial nerves on one side).

Midbrain syndromes.

Weber syndrome. Weber syndrome, or superior alternating hemiplegia, involves the cerebral peduncle and the fascicles of the oculomotor nerve on one side, causing ipsilesional oculomotor nerve palsy and contralesional hemiparesis; occasionally, the substantia nigra can also be involved. The syndrome was described in 1863 by Sir Hermann David Weber (1823-1918), a German-born physician working in London (142; 150).

Sir Hermann David Weber (1823-1918)

Sir Hermann David Weber was a German-born physician working in London, in 1902. Painting Hubert von Herkomer (1849-1914). (Courtesy of Bushey Museum and Art Gallery, Bushey, England. Public domain.)

Benedikt syndrome. Benedikt syndrome, a paramedian midbrain stroke syndrome that involves the fascicles of the oculomotor nerve and the red nucleus, was first described by Hungarian-Austrian neurologist Moritz Benedikt (1835-1920) in 1889 (15; 149). French neurologist Jean-Martin Charcot (1825-1893) named the syndrome with the eponym Benedikt syndrome in 1893 (22).

Claude syndrome. Claude syndrome, ipsilesional oculomotor nerve palsy and contralesional limb ataxia, was first described by French neurologist Henri Claude (1869-1945) in 1912 (24; 24).

French neurologist Henri Claude (1869-1945)

(Source: Bibliothèque interuniversitaire de Santé, Paris. Licence Ouverte/Open Licence.)

Nothnagel syndrome. In 1879, German internist Carl Wilhelm Hermann Nothnagel (1841-1905) described a rare syndrome of the midbrain tectum that involves the oculomotor nerve fascicles and superior cerebellar peduncle, causing bilateral oculomotor nerve palsy and limb ataxia, respectively (99; 100; 79).

German internist Carl Wilhelm Hermann Nothnagel (1841-1905)

(Source: Photograph by Josef Löwy [1834-1902], Sport & Salon, December 27, 1902. Public domain.)

Pontine syndromes.

Raymond syndrome. In 1896, French neurologist Fulgence Raymond (1844-1910) described a ventral medial mid-pontine syndrome with ipsilesional abducens palsy and contralesional central facial paresis and hemiparesis (110; 148).

Defoville (Foville) syndrome. Defoville syndrome (sometimes called Foville syndrome) is a rare inferior medial pontine syndrome first characterized in 1858 by French psychiatrist and neurologist Achille Louis François Foville (1831/1832-1887) (40; 146; 18). On the title page of his doctoral thesis in 1837, Foville spelled his name "Defoville" to distinguish himself from his father, Achille Louis Foville (1799-1878), who was an anatomist, psychiatrist, and neurologist. The syndrome consists of ipsilesional horizontal gaze palsy, peripheral facial palsy, and contralesional hemiparesis resulting from a lesion in the lower pons.

Superior cerebellar artery syndrome. In 1908, and in more detail in 1912 with the results of autopsy, Philadelphia neurologist Charles Karsner Mills (1845-1931) described the superior cerebellar artery syndrome in a 34-year-old man with a history of syphilis who presented initially with vertigo, nausea and vomiting, left arm clumsiness, right emotional facial palsy, and right-sided sensory impairment that involved the face, limbs, and trunk (88; 89; 129). At autopsy, Mills and neurologist and pathologist William Gibson Spiller (1863-1940) found a lesion involving the cerebellum and dentate nucleus, the superior cerebellar peduncle, and the red nucleus on the opposite side, with the main symptoms being ataxia of the extremities ipsilateral to the main lesion (intention tremor, dysmetria, and asynergia) and contralateral "deafness, paralysis of emotional expression in the face, and loss of the senses of pain, heat and cold over the entire half of the body" (89; 129; 29).

Anterior inferior cerebellar artery syndrome. In 1943, American neurologist and neuropathologist Raymond Delacy Adams (1911-2008) first described the clinical and pathologic features of occlusion of the anterior inferior cerebellar artery (02).

American neurologist and neuropathologist Raymond Delacy Adams (1911-2008)

(Source: Courtesy of Robert Laureno MD. Edited by Dr. Douglas J Lanska.)

The so-called Millard-Gubler syndrome. According to recent formulations, the so-called Millard-Gubler syndrome, caused by a unilateral lesion in the ventral pons, manifests as an ipsilateral palsy of cranial nerves VI and VII with contralateral hemiplegia. In fact, the original descriptions of Millard and Gubler did not include cranial nerve VI paresis. Nor did they include gaze paresis, facial sensory loss (cranial nerve V), vertigo, or deafness (cranial nerve VIII).

The Millard-Gubler syndrome, as described in 1856 by the two eponymous French physicians Auguste Louis Jules Millard (1830-1915) and Adolphe-Marie Gubler (1821-1879), was simply a crossed paresis of the peripheral facial nerve on one side and a contralateral hemiparesis (50; 87; 145). Millard and Gubler separately described patients with this combination of signs due to a lesion of the pons--a classic crossed brainstem syndrome. However, modern references to this syndrome are almost all in error in defining the syndrome as involvement of both the sixth and seventh cranial nerves on one side, typically with a contralateral hemiparesis; this combination would indicate involvement of the caudal pontine tegmentum, sparing the abducens nucleus (which would produce a gaze palsy) and medial structures (paramedian pontine reticular formation and medial longitudinal fasciculus, which together would produce a one-and-a-half syndrome). Gubler’s cases included three with a tumor, one with a stroke, and one with a brownish softening, whereas Millard reported one case due to pontine hemorrhage. Millard's case was described in a letter to the editor in the journal where Gubler reported his cases. None of these cases had a reported ocular motility disturbance or vertigo. The lesions must have all involved the basis pontis as well as the CN VII fascicle (and possibly the facial nerve nucleus) but could not have extended more medially or dorsally to involve the CN VI nucleus or fascicle or the paramedian pontine reticular formation, nor could they have extended further laterally and dorsally to involve CN VIII or the cochlear and vestibular nuclei. The eponym is erroneously applied to a combined CN VI and CN VII lesion. The original reports were translated by Wolf, who correctly emphasized that neither Millard nor Gubler reported a CN VI paresis, but who then suggested that the syndrome was due to involvement of the facial nerve nucleus, when it is also possible for it to involve the facial nerve fascicle (50; 87; 145).

Medullary syndromes.

Lateral medullary syndrome (Wallenberg syndrome). Prussian internist, neurologist, and neuroanatomist Adolf Wallenberg (1862-1949) is most remembered for his eponymous clinical and pathological descriptions of the lateral medullary syndrome (Wallenberg syndrome) (139; 140; 143; 147; 14; 74; 75; 125). Wallenberg’s detailed clinical (but not pathological) description in 1895 (139) preceded American neurologist Henry Hun’s (1854-1924) clinicopathological description in 1897 (56; 74), but both reports were partially anticipated by others.

Based on his knowledge of neuroanatomy, Wallenberg had correctly localized his patient’s lesion to the lateral medulla and attributed it to occlusion of the posterior inferior cerebellar artery. Still, it was not until 1901, 4 years after Hun’s clinicopathological report, that Wallenberg reported the pathological findings on his patient, who died in 1899 (139; 140). Wallenberg thought the syndrome in his case was due to embolization of the posterior inferior cerebellar artery (139; 140); however, the most common cause is thrombosis of the vertebral artery.

Wallenberg’s patient, a 38-year-old man, presented with an attack of vertigo associated with pain and hyperesthesia on the left side of the face and body, hypoesthesia of the right half of the face, and loss of pain and temperature sensitivity in the right extremities and the right half of the torso, with retention of the sense of touch (139). He also had dysphagia; impaired sensation on the mucosa of the mouth, throat, and palate; disturbed motility of the soft palate (on the first day bilateral, later left-sided); hoarseness with paralysis of the left vocal cord, and paresis of the left hypoglossal muscle, with no disturbance in the innervation of the facial muscles. He had ataxia of the left extremities without impairment of gross strength and a marked tendency to fall to the left side. At autopsy, the most extensive atherosclerotic changes were in the left vertebral artery and its branches, including a near occlusive thrombus in the left posterior inferior cerebellar artery.

Hun’s 53-year-old patient had acutely developed ipsilesional ptosis and anhidrosis (but reportedly not miosis), diplopia, ipsilesional analgesia and thermanesthesia of the face, dysphagia, dysphonia, dysarthria, ipsilateral appendicular ataxia, postural instability with a tendency to fall toward the side of the lesion, gait ataxia, contralesional analgesia and thermanesthesia of the body, and vomiting (56; 74). Pathological findings included extensive posterior circulation atherosclerosis, affecting especially the basilar artery, and infarction of the rostral lateral medulla, encompassing the descending trigeminal nucleus and tract, the nucleus ambiguous, the lateral spinothalamic tract, the ventral spinocerebellar tract, fasciculi of the glossopharyngeal and vagal nerves, and the inferior cerebellar peduncle (56; 74). Hun concluded that the manifestations resulted from left posterior inferior cerebellar artery occlusion.

Opalski syndrome. Shortly after World War II, Polish neurologist Adam Opalski (1897-1963) described a rare variant of Wallenberg syndrome with ipsilateral hemiparesis (104; 114).

Medial medullary syndrome. Medial medullary infarction was initially described by William Gibson Spiller (1863-1940) in 1908 (128). In 1914, French neurologist Joseph Jules Dejerine (1849-1917) proposed a diagnostic triad of symptoms: (1) contralateral hemiplegia sparing the face, (2) contralateral loss of deep sensation, and (3) ipsilateral hypoglossal paralysis (31).

French neurologist Joseph Jules Dejerine (1849-1917)

(Source: Wellcome Collection, London, UK. Public domain.)

Babinski-Nageotte and Cestan-Chenais syndromes. French-Polish neurologist Joseph Babinski (1857-1932) and French neuroanatomist Jean Nageotte (1866-1948) described an intermediolateral medullary syndrome in 1902 (09; 10). Babinski-Nageotte syndrome essentially incorporates lateral medullary syndrome with contralateral hemiparesis or hemiplegia because of extension of the “Wallenbergian” lateral lesion to the corticospinal tract.

Cestan-Chenais syndrome was described by French neurologist Étienne Jacques Marie Raymond Céstan (1872-1934) and French physician Louis Jean Chenais (1872-1950) in 1903 (20). Cestan-Chenais syndrome includes all symptoms of Babinski-Nageotte syndrome except the ipsilateral hemiataxia because of sparing of the posterior spinocerebellar tract (20; 71).

Reinhold hemimedullary syndrome. German physician Heinrich Reinhold (1862-1927) described the hemimedullary syndrome in 1894 (111; 64). The hemimedullary syndrome is essentially a combination of the lateral and medial medullary syndromes.

Hemimedullary syndrome results from occlusion of a vertebral artery proximal to the posterior inferior cerebellar artery and its anterior spinal artery branches (71).

Avellis syndrome. Avellis syndrome was described by German otolaryngologist Georg Avellis (1864-1916) in 1891 (08). Avellis described 10 cases in which there was unilateral paralysis of the larynx associated with paralysis of the soft palate on the same side. None of the 10 cases came to autopsy. The term "Avellis syndrome" was coined by French otolaryngologist Marcel Lermoyez (1858-1929). Because the Milanese otologist Giovanni Longhi (1843-1893) reportedly described patients with similar symptoms, the syndrome is sometimes referred to as Avellis-Longhi syndrome or Longhi-Avellis syndrome.

Numerous closely related syndromes involving the vagus nerve have been described (59). In 1918, Vernet reviewed the various syndromes associated with laryngeal paralysis and presented a classification of them (137). Since then, others have been added, and further classifications have been presented, only some of which involve the brainstem (57; 61; 141; 131; 63; 68; 69; 109; 55; 72; 54; 156). Many involve the jugular foramen or the extramedullary cranial nerves within the subarachnoid space or extracranially (76; 41).

Table 1. Syndromes Associated with Laryngeal Paralysis and Other Cranial Nerves

Cranial Nerves

IX

X

XI

XII

Vocal Cord

Palate

Collet and Sicard

*

*

*

*

*

Jackson

*

*

*

*

Vernet

*

*

*

*

Schmidt

*

*

*

Avellis

*

*

Tapia

*

*

Villaret

*

*

*

*

Lederer proposed a simplified system that avoided eponyms (76), an approach that was supported by subsequent authors (41; 28).

Table 2. Lederer's Segmental System for Classifying Lesions Involving the Vagus Nerve

Syndrome

Cranial Nerves Involved

Bulbar

X and variable combinations of IX, XI, XII (and possibly V, VI, VII, VIII)

Jugular foramen

X and IX, XI, XII and sympathetic

Parapharyngeal space

X and IX, XII (possibly VII) and sympathetic

Arch of aorta

X and phrenic, sympathetic