{'fraction_non_alphanumeric': 0.03932048100782592, 'fraction_numerical': 0.014315709104790991, 'mean_word_length': 5.55, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 3, 'https://': 0, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Segmental Myoclonus and Epilepsy in a Child with GAD 65 Antibodies

Glutamic acid decarboxylase (GAD) is a rate-limiting enzyme for the synthesis of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter. It is widely distributed in the central nervous system but is also present in other organs, especially the pancreas. Elevated GAD 65 antibodies have diverse clinical associations, including stiff person syndrome (SPS), cerebellar ataxia, limbic encephalitis, epilepsy, ocular motor disorders, type 1 diabetes mellitus, and rarely myoclonus. GAD 65 antibody-associated neurological syndromes, mostly SPS or epilepsy, are rarely reported in pediatrics. Many patients improve after immune therapy and some, whose presentation includes seizures, become seizure free. Elevated GAD 65 antibodies may be associated with tumors. However, such an association is rare in children. A 7.5year-old-girl, previously healthy and intellectually normal, presented with a few days history of self-limited right-sided throbbing headache and a new-onset focal tonic– clonic seizure with bilateral spread lasting 5 min. She concurrently developed right sided then bilateral continuous, high frequency, semi-rhythmic facial muscle twitching, consistent with myoclonus, most prominent on the right face and upper lip (Video). The myoclonus was present during wakefulness and sleep. Six weeks later, the myoclonus spread to her right thumb and tongue. She did not develop myoclonus anywhere else. She did not feel the myoclonus. The myoclonus responded partially to treatment with clonazepam. Levetiracetam was started following a second, 2.5 min focal unaware seizure, 10 d after the first seizure. There were no signs of encephalopathy, cognitive decline, or regression. She could eat, drink, and speak normally. Pregnancy, delivery, development, and past medical history were unremarkable. Parents are non-consanguineous. There was no family history of seizures, autoimmune, or movement disorders. The patient’s full neurological exam was normal apart from the myoclonus. Blood tests were normal including CBC, extended electrolytes, glucose, liver and thyroid function, uric acid, copper, ceruloplasmin, ESR, CRP, C3, C4, immunoglobulins, rheumatoid factor, ANCAs, anti-TPO, and phospholipid (cardiolipin and β2-glycoprotein) antibodies. ANA screen was positive (low titers at 1:40 for speckled and 1:80 for nucleolar antinuclear antibodies detected by immunofluorescence), but dsDNA and extractable nuclear antigens were negative. Urinary vanillylmandelic acid and homovanillic acid were negative. CSF investigations revealed normal glucose and lactate, with a slightly elevated protein (0.29 g/l, normal range: 0.12–0.24) and cell count (8 cells, 97% lymphocytes). Oligoclonal bands were present in the CSF with no corresponding bands in the serum. GAD 65 antibodies were ‘highly positive’ in CSF and serum as tested by a cell-based immunoassay (CBA: Euroimmun AG, Luebeck, Germany), performed by MitogenDx, Calgary, Canada. Serum level of anti-GAD 65 as tested by an enzyme-linked immunosorbent assay (ELISA) was >250 IU/ml (normal range< 5 IU/ml). Other autoimmune encephalitis and paraneoplastic antibodies (CBA and line immunoassay, respectively: Euroimmun) including NMDA, DPPX, VGKC, AntiGABAB receptor profile, AMPA antibodies were negative. Neoplastic work up was negative including chest, abdomen, and pelvic MRI at presentation and 1 year later. The first brain MRI showed an asymptomatic Chiari I malformation with no other abnormalities. Follow-up MRI 6 and 10 weeks later showed sequential development of left then right mesial temporal lobe hyperintensities (Figure 1). Whole-body positron emission tomography (18 F FDG-PET) to further look for potential neoplasm showed intense asymmetric activity, right > left, in the nasopharynx and oropharynx from the myoclonus. Intense uptake was seen in thenar muscles of the right hand. No other abnormality was identified in the brain or elsewhere. The initial EEG captured continuous 7–9 Hz muscle artifacts from the myoclonus during wakefulness, which decreased during sleep, becoming more prominent on the right side, and not associated with epileptiform discharges. An EEG 7 weeks later showed left hemisphere slowing and multifocal epileptiform discharges with interictal left temporal epileptiform activity occurring in runs at times and infrequent left frontal and bilateral frontopolar interictal epileptiform activity (Figure 2). Surface and needle EMG showed bilateral semirhythmic facial muscle discharges consistent with a subcortical origin. The patient was diagnosed with GAD 65 antibody-associated neurological disease. Four months after presentation, she was started on immunosuppressive therapy according to the BrainWorks protocol (http://www.sickkids.ca/PDFs/Research/Brain Works/63976-Antibody%20IBrainD.pdf): IV methylprednisolone Figure 1: Axial FLAIR brain MRI (TR 9890, TE 90) demonstrating bilateral asymmetric (right > left) hyperintense signal abnormalities (arrows) within the uncus and adjacent parahippocampal gyri 3 months after presentation, which improved 9 months later and resolved 2 years after presentation. LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES