Metabolic causes of pediatric developmental & epileptic encephalopathies (DEE)- genetic variant analysis in a south Indian cohort.

PURPOSE: Drug-resistant epilepsy is seen in patients with inborn errors of metabolism and metabolic dysfunction in neurons is crucial to brain disorders associated with psychomotor impairment. Diagnostic rates of metabolic causes of developmental and epileptic encephalopathy (DEE) using next generation sequencing have been rarely studied in literature. METHODS: A prospective hospital study was carried out in 384 children with DEE, who underwent genetic testing. Metabolic disorders were evaluated with biochemical blood/urine assays and when required CSF estimations performed. RESULTS: A total of 154 pathogenic/likely pathogenic variants in 384 children were identified. Out of 384 children, 89 were clinically suspected to have probable or possible metabolic disorders. Pathogenic/likely pathogenic variants in metabolic genes were identified in 39 out of 89 (43.8 %) and promising VUS in 28 (31.4 %). These included variants for progressive myoclonus epilepsies (21; 53.8 %), DEE with focal/multifocal seizures (8; 20.5 %), generalized epilepsy (5;12.8 %), early myoclonic encephalopathy (2; 5.1 %), LGS (1; 2.6 %) and West syndrome (2; 5.1 %). CONCLUSION: Our cohort demonstrates for the first time from the Indian subcontinent that identification of metabolic variants can guide investigations and has therapeutic implications in patients with variable DEE phenotypes. A high utility is noted with regard to diagnosis and prognostication, given the low yield of available biochemical tests, indicating cost-effectiveness of this approach.

Predictors of outcome in super refractory status epilepticus.

PURPOSE: We conducted this study to determine the clinical, electrophysiological and radiological predictors of outcome in Super Refractory Status Epilepticus (SRSE). METHODS: Data of patients treated for SRSE between January 2000 and November 2019, archived prospectively in our SE registry were analyzed. Functional outcome was measured by Glasgow outcome score (GOS) at the time of hospital discharge and was divided into: good i.e. GOS ≥ 3 and bad outcome i.e. GOS < 3. The predictors of outcome were determined using appropriate statistical tests by univariate and multivariate analysis, p < 0.05 was considered as statistically significant. RESULTS: Of the 384 patients with status epilepticus (SE) identified during the study, 28 (8%) were diagnosed as SRSE and were included in the final analysis. Acute symptomatic SE comprising 15 (53.6%) patients was the most common etiology of SRSE. Thirteen patients (three patients with viral encephalitis and 10 patients with clinically possible autoimmune encephalitis) had New Onset Refractory Status Epilepticus (NORSE) like clinical presentation.12 patients (42.9%) had good outcome and 16 patients (57.1%) had bad outcome. Multivariate logistic regression analysis showed that independent predictors of poor outcome were: duration of ICU stay (p < 0.001); EEG findings such as non-convulsive SE in coma (0.032), spontaneous burst suppression (0.001) and postictal diffuse attenuation (<0.001); delay in starting anesthesia (0.002); and delay in starting immunotherapy in NORSE due to autoimmune encephalitis (0.002). CONCLUSION: We could determine independent therapeutic and electrophysiological prognostic factors for SRSE. Early initiation of treatment and stringent management of these factors especially in an younger age-group, aided by continuous EEG monitoring and a thorough etiological work-up can result in good outcomes in more than one-third of cases.

Mucopolysacharidosis Type I Presenting as Bipolar Affective Disorder: A Case Report.

Mucopolysacharidosis type I is a multisystem disease and often presents with neurobehavioral problems, corneal clouding, cardiac valve involvement, hepatomegaly, coarse facies, and skeletal abnormalities. It has three subtypes - with Hurler subtype (MPS-1H) being the most severe phenotype with early neurological involvement, rapid progression and mortality, while the other two subtypes - Hurler-Scheie (MPS-1H/S) and Scheie (MPS-1S) are of intermediate and milder severity, respectively. Even though neuropsychiatric symptoms have often been reported in the pediatric age group, MPS type I presenting as a major psychiatric illness in adulthood has rarely been reported in literature. Here, we report a female presenting as bipolar affective disorder in the fourth decade of life, where neuroimaging and systemic involvement gave a clue to the diagnosis.

Multifocal cavitating leukodystrophy-A distinct image in mitochondrial LYRM7 mutations.

An adult woman presented with insidious onset slowly progressive symmetric spasticity and mild upper extremity dysmetria, with sparing of bowel and bladder functions. She had a distinct magnetic resonance imaging (MRI) pattern of bilateral symmetrical T2 hyperintensity involving periventricular especially parieto-occipital and deep cerebral white matter with multifocal small cavitations which were posterior predominant, sparing subcortical U fibres. Magnetic resonance spectroscopy (MRS) showed lactate peak. Her clinical exome sequencing revealed a pathogenic homozygous start-loss variation in exon 1 encoding the mitochondrial LYR motif-containing protein 7 (LYRM7 gene) which is an integral part of complex III of the mitochondrial respiratory chain. Our case was unique in the indolent adult onset leukodystrophy like presentation making her wheel chair bound by the fourth decade, while most reported patients to date had an early childhood presentation as repeated episodes of subacute leukoencephalopathy with motor regression or death by first decade. Myriad phenotypic presentation of the LYRM7 gene mutations reported till date is highlighted.