Evan Cole Lewis

Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood

Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information. Results: Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder. Conclusions: We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent.

Central Nervous System Vasculitis With Positive Antithyroid Antibodies in an Adolescent Boy

Hashimotos encephalopathy is diagnosed when patients exhibit features of corticosteroid-responsive encephalopathy and positive antithyroid antibodies. The relationship between antithyroid antibodies and encephalopathy is subject to considerable debate. We describe corticosteroid-responsive encephalopathy in a 14-year-old boy with positive antimicrosomal antibodies. His history included subtle neurocognitive decline. He presented with seizures. He underwent a brain biopsy before initiating treatment after his third episode. That biopsy was consistent with central nervous system vasculitis. This report is unique because, to our knowledge, it describes the first pretreatment brain biopsy of a pediatric patient who fits the criteria for Hashimotos encephalopathy.

COL4A1 mutation in a pediatric patient presenting with post-ictal hemiparesis.

a six-year-old girl presented with a prolonged left sided paresis and acute complete right hemispheric injury of uncertain mechanism following an episode of convulsive status epilepticus. She was born at full term after an uneventful pregnancy. at day two of life, she had three consecutive seizures and magnetic resonance imaging (MRi) revealed an intraparenchymal small bleed in the right frontal lobe. Full coagulation workup was done which was negative. She was successfully treated with phenobarbital. Follow-up MRi at seven months revealed right frontal porencephaly and volume loss of the right hemispheric subcortical white matter, basal ganglia, thalami, cerebral peduncle and corpus callosum. abnormal signal in the right cerebellar hemisphere was also identified. at 12 months-of-age, brain computed tomogram angiography indicated no evidence of arteriovenous malformations. Electroencephalogram (EEG) at 18 months-of-age showed a mildly disorganized background for age and asymmetry throughout the recording with lower amplitudes in the right hemisphere. Neurological examinations were consistently abnormal with increased reflexes on the left and a tendency to favor her right side. at two years-of-age, repeat MRi with MRa was unchanged and there was no evidence of vasculopathy (Figure1a). She remained seizure-free. Pheno-barbital was discontinued and she was discharged from follow-up. the child then presented to our emergency department at six years-of-age with a generalized tonic-clonic seizure that lasted 35 minutes and was aborted with intravenous lorazepam and dilantin. Seizure onset was not witnessed, however several hours earlier she had awoken from sleep with a headache, sore throat, malaise and complaints of being warm. Physical examination after recovery from her seizure revealed normal vitals and she was afebrile. She was found to have dysarthria, a left homonymous hemianopsia, a left dense hemiparesis, and left sided upper motor neuron signs including a left extensor plantar response. blood work including cultures, extractable nuclear antigen, antinuclear antibodies, and a coagulation profile were all normal. a cardiology assessment including electrocardiogram and echocardiogram were normal. brain MRi demonstrated diffuse right cortical and subcortical edema with associated reduced diffusivity of water motion in the right hemisphere, involving areas supplied by both the anterior and posterior circulations (Figure 2). the MRa studies indicated no evidence of a vascular malformation or vessel abnormalities. Previously described structural abnormalities were unchanged. an EEG revealed abnormal background and right-sided diffusely low COL4A1 Mutation in a Pediatric Patient Presenting with Post-Ictal Hemiparesis