Cogan syndromeis a disorder which is probably over- looked. It affects young adults and is characterized
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by episodes of acute interstitial keratitis with vestibu- loauditory dysfunction (Cogan, 1945). From 2% to 50% of patients present with neurological deficits, mainly meningoencephalitis, seizures, organic men- tal syndrome, and peripheral neuropathy. Patients may present with thrombosis of the PICA artery or multiple acute cerebellar lesions mimicking cerebellar infarc- tions (Norton & Cogan,1959; Fair & Levi,1960; Manto
& Jacquy,1996).The diagnosis should be considered in any patients presenting with a combination of eye and ear symptoms with cerebellar signs.The pathogenesis consists of a vasculitis. Cerebellar ataxia may improve with steroids (Manto & Jacquy,1996).
Behc¸et disease usually starts between 16 and 55 years of age, with a predominance in males. The disorder is a vasculitis characterized by a triad of oral and genital aphthous ulcers, meningoencephali- tis, and relapsing uveitis. The disease has a wide systemic spectrum, involving joints, nervous system, gastrointestinal tract, and vessels. About 10% to 25%
of patients exhibit neurological deficits (Nakasu et al., 2001; Wolf et al,1965; Hadfield et al., 1997). Usually, patients have fever during or preceding CNS manifes- tations (O’Duffy & Goldstein,1976).The most com- mon symptoms of neuro-Behc¸et disease are headache, paresthesia, unsteadiness, diplopia, and weakness (Ashjazadeh et al., 2003). Neurological examina- tion shows various combinations of gait deficits, sensory abnormalities, ophthalmoplegia, cerebellar ataxia, pseudobulbar syndrome, and hemiplegia.The most common presentation is a “brainstem-plus”
type. Intracranial hypertension is not rare. Suba- cute onset or a relapsing-remitting course may first suggest a multiple sclerosis (MS). Patients are par- ticularly at risk for venous sinus thrombosis, arte- rial occlusion, or thrombophlebitis. Most intra-cranial aneurysms which have been described are located supra-tentorially. The superior cerebellar artery is a potential site (Ho & Deruytter, 2005). The most common neuropathologicfindings are focal necrotic lesions in the brain. Perivascular inflammation is par- ticularly marked (Arai et al, 2006). Although some aneurysms disappear after steroid therapy, others require surgery, keeping in mind that aneurysms may be the site of an inflammatory process and therefore are friable (Nakasu et al., 2001; Chun et al., 2001).
Regarding CSF, neuro-Behc¸et disease is characterized by pleocytosis with predominant lymphocytosis, as well as elevated protein levels (O’Duffy & Goldstein, 1976). MRI is the investigation of choice, revealing
iso-/hypointense lesions in T1-weighted images and hyperintense lesions in T2-weighted images, mainly in the mesodiencephalic junction, cerebellar pedun- cles, or other brainstem areas (Haghighi et al.,2005).
Steroids are usually effective to reduce or stop the progression of the neurological deficits. Immuno- suppressive agents used are cyclophosphamide, aza- thioprine, and chlorambucil (Benamour et al.,2006).
Anticoagulation and anti-epileptic agents may be required for dural sinus thrombosis. The progno- sis is usually worse in cases of parenchymal CNS involvement.
Systemic lupus erythematosusmay affect cerebellar structures in an acute or subacute mode. Patients are at risk for acute vasculopathy in the territory of cere- bellar arteries or may develop a subacute pancerebel- lar syndrome (Manto et al.,1996; Chan et al.,2006;
Parikh et al.,2007). Multiple infarctions in the verte- brobasilar territory may be the initial manifestation (Kwon et al.,1999). Sj¨ogren syndrome and Hashimoto encephalopathy might share some pathophysiological mechanisms with lupus. Antibodies directed against Purkinje cells have been reported in patients with lupus ataxia (Shimomura et al., 1993). Treatments include prednisone, cyclophosphamide, and anticoag- ulation. Ataxia may respond promptly to steroids in some cases.
Polyarteritis nodosa is characterized by a necro- tizing arteritis of small and medium arteries. The disorder manifests from childhood to midlife and affects mainly the skin, joints, kidneys, gastrointesti- nal tract, and peripheral nerves in a context of fever and weight loss (Conn,1990). Hypertension is com- mon. CNS involvement includes diffuse encephalopa- thy, focal deficits, and seizures. Infarctions are found in the cortical and subcortical regions of cerebral hemi- spheres, in basal ganglia, internal capsule, brainstem, and cerebellum (Provenzale & Allen,1996). Cerebral angiography shows alternating sites of narrowing and dilatation in middle-size and small arteries, con- sistent with arteritis. Diagnosis can be confirmed by nerve, muscle, or kidney biopsy. Neurological symptoms usually respond to steroid and cytotoxic agents.
Auto-immune polyglandular syndromes (APS) comprise a wide spectrum of auto-immune disorders and are divided into a rare juvenile (PAS type I) and a more common adult type with (PAS II) or without adrenal failure (PAS III) (Kahaly, 2009). Autosomal recessive PAS I is caused by mutations in the
108
A C D
E F G H
B
Figure 9.1 Auto-immune polyglandular syndrome (APS) type 2 in a young man presenting with a disabling cerebellar syndrome. (A,B) T2-weighted brain MRI. Cerebellar sulci are widened (A). There is a moderate cerebral diffuse cortical atrophy (B). (C,D) Single-photon emission CT imaging showing an asymmetry of cerebellar blood flow, with hypoperfusion of right cerebellar hemisphere (arrows). (E–H)
18F-Fluorodeoxyglucose positron emission tomography study shows an asymmetry of cerebellar metabolism and a diffuse cerebral cortical hypometabolism.
auto-immune regulatory (AIRE) gene on chro- mosome 21. Mutations in the AIRE gene result in defective proteins which cause auto-immune destruc- tion of target organs. Neurologic deficit may result from the associated endocrinopathies (hypoparathy- roidism, hypothyroidism, diabetes mellitus), vitamin deficiencies (vitamins B12 and E), and celiac sprue (Berger et al., 2008). Cerebellar syndrome may be prominent in APS type I or type II. Brain MRI can demonstrate a cerebellar atrophy, and positron emission tomography studies can reveal a cerebellar hypometabolism (Figure 9.1). Diagnosis of PAS involves serological measurement of organ-specific autoantibodies and subsequent functional testing.
Vogt-Koyanagi-Harada diseaseis an inflammatory disorder characterized by posterior uveitis, iridocy- clitis, and papillitis. Hair loss and vitiligo are com- monly observed. Patients may present with diplopia, dysarthria, and cerebellar ataxia as a result of a brain- stem encephalitis extending into the middle cerebel- lar peduncle (Hashimoto et al.,2009). Wallenberg syn- drome due to stroke is a complication. Ataxia may respond to administration of steroids.
Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis)is a benign and self-limiting disease of unknown etiology affecting mainly young women. It presents with localized lymphadenopathy, usually cer- vical, accompanied by various systemic manifestations including fever, weight loss, night sweats, leukopenia, and high erythrocyte sedimentation rate. Patients may present with acute aseptic meningitis. Kinetic tremor and gait ataxia may precede cervical lymphadenopathy (Moon et al.,2009). Diagnosis is based upon the biopsy of cervical lymph nodes, showing areas of necrosis with abundant debris and reactive histiocytes. Acute cerebellar symptoms resolve spontaneously. Kikuchi- Fujimoto disease has been described in association with other auto-immune disorders, mainly systemic lupus erythematosus.
Graft-versus-host disease after a bone-marrow transplant is a cause of cerebral vasculitis (Camp- bell & Morris, 2005). Lesions may predominate in the cerebellum. Cerebral angiography shows dilated and narrowed segments of the posterior circulation.
Steady improvement with immunosuppressant ther-
apy is reported.
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