Delayed transhemispheric propagation of electrographic seizures following functional hemispherectomy

Objective:To determine the association between electroencephalographic seizure (ES) and electroencephalographic (ESE) exposure and unfavorable neurobehavioral outcomes in critically ill children with acute encephalopathy.Methods:This was a prospective cohort study of acutely encephalopathic critically ill children undergoing CEEG. ES exposure was assessed as: (1) no ES/ESE, (2) ES, or (3) ESE. Outcomes assessed at discharge included the Glasgow Outcome Scale - Extended Pediatric Version (GOS-E-Peds), Pediatric Cerebral Performance Category (PCPC), and mortality. Unfavorable outcome was defined as a reduction in GOS-E-Peds or PCPC score from pre-admission to discharge. Stepwise selection was used to generate multivariate logistic regression models that assessed associations between ES exposure and outcomes while adjusting for multiple other variables.Results:Among 719 consecutive critically ill subjects, there was no evidence of ES in 535 subjects (74.4%), ES in 140 subjects (19.5%), and ESE in 44 subjects (6.1%). The final multivariable logistic regression analyses included ES exposure, age dichotomized at 1-year, acute encephalopathy category, initial EEG background category, comatose at CEEG initiation, and the Pediatric Index of Mortality 2 score. There was an association between ESE and unfavorable GOS-E-Peds (Odds Ratio 2.21, 95%CI 1.07-4.54) and PCPC (Odds Ratio 2.17, 95%CI 1.05-4.51) but not mortality. There was no association between ES and unfavorable outcome or mortality.Conclusions:Among acutely encephalopathic critically ill children, there was an association between ESE and unfavorable neurobehavioral outcomes, but no association between ESE and mortality. ES exposure was not associated with unfavorable neurobehavioral outcomes or mortality.

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mTOR Inhibitors as a New Therapeutic Strategy in Treatment Resistant Epilepsy in Hemimegalencephaly: A Case Report

Journal of Child Neurology ◽

10.1177/0883073818813238 ◽

2018 ◽

Vol 34 (3) ◽

pp. 132-138 ◽

Cited By ~ 8

Author(s):

Qi Xu ◽

Shimrit Uliel-Sibony ◽

Christopher Dunham ◽

Harvey Sarnat ◽

Laura Flores-Sarnat ◽

...

Keyword(s):

Therapeutic Strategy ◽

Mtor Inhibitor ◽

De Novo ◽

Mtor Inhibitors ◽

Mtor Pathway ◽

Definitive Treatment ◽

Malformations Of Cortical Development ◽

Treatment Resistant ◽

Seizure Reduction ◽

Functional Hemispherectomy

Hemimegalencephaly is a hamartomatous malformation of one hemisphere. Functional hemispherectomy, the definitive treatment, is associated with significant morbidity and mortality in early infancy. Dysregulation of the mTOR pathway can result in malformations of cortical development, and mTOR inhibitors can effectively reduce seizures in tuberous sclerosis complex. We report a 6-day-old female with hemimegalencephaly and frequent seizures despite 9 antiseizure medications. At 3 months of age, while awaiting hemispherectomy, an mTOR inhibitor, rapamycin, was initiated by the neurologist. After 1 week of treatment, there was >50% reduction in seizures and total seizure burden, and after 2 weeks, development improved, resulting in deferral of surgery by 2.5 months with an increased body weight. Pathology demonstrated cortical dysplasia with upregulation of the mTOR pathway. Deep-sequencing of brain tissue demonstrated 16% mosaicism for a pathogenic de novo MTOR gene mutation. This case exemplifies how mTOR inhibitors could be considered for seizure reduction in patients with hemimegalencephaly while awaiting surgery.

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