Encephalitogenic Myelin Oligodendrocyte Glycoprotein


Cerebellum. nystagmus (Skillet), ocular flutter, opsoclonus and impaired easy pursuits.[4,5] The occurrence of upbeat nystagmus in GAD 65 associated CA is uncommon. Hereby, we describe a 52-year-old lady with seropositive GAD65 antibodies who presented with slowly progressive ataxia with dysarthria and gravity impartial upbeat nystagmus. A 52-year-old lady presented with history of gait unsteadiness since 1 year. Gait unsteadiness was insidious in onset and slowly progressive with no diurnal variance. She was able to ambulate on her own with occasional need of support at the time of presentation. She experienced tremulousness of both upper limbs on target oriented activities like holding glass of water, placement of morsel of food into the mouth, etc., slurring of speech in the form of scanning speech and vertiginous sensation while walking since 6 months. There was no headache, seizures, myoclonus, cognitive, or behavioral disturbance. There was no family history of comparable complaints. She did not have any medical comorbidity. Systemic examination was unremarkable. Cognitive assessment was normal. GSK2190915 She had scanning dysarthria. Fundus examination was normal. Saccades and pursuit were normal. Upbeat nystagmus was noted on asking her to look up with fast phase up both in supine and upright GSK2190915 position [Videos 1 GSK2190915 and 2; consent taken]. There was ill-sustained horizontal gaze-evoked nystagmus. Motor and sensory examination was normal. She experienced bilateral fingerCnose incoordination, dysdiadochokinesia, kneeCheel incoordination and gait ataxia. CDX4 Plantar responses were flexor. Program blood examination including thyroid function test was within normal limits. Glycosylated hemoglobin was normal. Brain magnetic resonance imaging showed moderate cerebellar atrophy [Physique 1]. Serum anti-GAD 65 antibodies were strongly positive (qualitative assay). Cerebrospinal fluid analysis was normal. Computed tomography of thorax and stomach was normal. She was treated with intravenous methylprednisolone (1 g for 5 days) with no improvement followed by large volume plasmapheresis (5 cycles on alternate days) with moderate improvement in gait. Open in a separate window Physique 1 Brain MRI T2 sagittal image (a) and (b) GSK2190915 axial image shows cerebellar atrophy (reddish arrow) Upbeat nystagmus is seen in patients with brainstem infarctions, hemorrhages, tumors, multiple sclerosis, Wernicke encephalopathy, epilepsy, brainstem encephalitis, Creutzfeldt-Jakob disease, Behcet syndrome, meningitis, Chiari malformation, and cerebellar degeneration. It occurs in pontomesencephalic, pontomedullary, and anterior vermis of cerebellum lesions.[6] The cause of spontaneous nystagmus in GAD65 associated CA is due to deficiency of GABAergic neurotransmission in cerebellum with or without brainstem involvement. Downbeat nystagmus is due to the dysfunction in flocculus/paraflocculus. PAN is due to the dysfunction of nodulus/uvula of cerebellum. The cerebellar flocculus inhibits anterior canal vestibular pathways though not the posterior canal pathways. As a result, GAD65 antibodies mediated reduced GABAergic inhibitory control of floccular Purkinje cells cause downbeat nystagmus.[4] The occurrence of upbeat nystagmus in GAD 65 associated CA is uncommon but has been reported. Martins em et al /em ., reported a 68-year-old lady with seropositive GAD65 antibodies who experienced paraoxysmal central positioning upbeat nystagmus in supine position. On upright position, there was asymptomatic downbeat nystagmus with alternating skew deviation.[7] GSK2190915 Feldman em et al /em ., reported a 72-year-old woman with progressive cerebellar ataxia, dysarthria of 1 1 year period, and upbeat nystagmus which was gravity impartial.[8] The involvement of afferents from your vestibular nuclei projecting to the flocculus through caudal medulla, and involvement of cerebellar feedback loop cause upbeat nystagmus which is gravity dependent.[9] The dysfunction of neural integrator for vertical gaze holding also causes upbeat nystagmus which is gravity independent.[10] We report a middle-aged lady with progressive pan-cerebellar syndrome with gravity impartial upbeat nystagmus and seropositive for GAD65 antibodies. The occurrence of upbeat nystagmus in GAD 65 associated CA widens the aetiology of upbeat nystagmus and provides a clue for the etiological diagnosis in patients presenting with late-onset cerebellar ataxia. Declaration of individual consent The authors certify that they have obtained all appropriate individual consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest You will find no conflicts of interest. Videos available on: Click here to view.(12M, mp4) Click here to view.(11M, mp4) Recommendations 1. Honnorat J, Saiz A, Giometto B, Vincent A, Brieva L, Andres C, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: Study of 14 patients. Arch Neurol. 2001;58:225C30..