A case of severe progressive early-onset epileptic encephalopathy: unique GABAergic interneuron distribution and imaging.

Early-onset epileptic encephalopathies include various diseases such as early-infantile epileptic encephalopathy with suppression burst. We experimentally investigated the unique clinicopathological features of a 28-month-old girl with early-onset epileptic encephalopathy. Her initial symptom was intractable epilepsy with a suppression-burst pattern of electroencephalography (EEG) from 7 days of age. The suppression-burst pattern was novel, appearing during sleep, but disappearing upon waking and after becoming 2 months old. The EEG showed multifocal spikes and altered with age. Her seizures demonstrated various clinical features and continued until death. She did not show any developmental features, including no social smiling or head control. Head MRI revealed progressive atrophy of the cerebral cortex and white matter after 1 month of age. (123)IMZ-SPECT demonstrated hypo-perfusion of the cerebral cortex, but normo-perfusion of the diencephalon and cerebellum. Such imaging information indicated GABA-A receptor dysfunction of the cerebral cortex. The genetic analyses of major neonatal epilepsies showed no mutation. The neuropathology revealed atrophy and severe edema of the cerebral cortex and white matter. GAD-immunohistochemistry exhibited imbalanced distribution of GABAergic interneurons between the striatum and cerebral cortex. The results were similar to those of focal cortical dysplasia with transmantle sign and X-linked lissencephaly with ARX mutation. We performed various metabolic examinations, detailed pathological investigations and genetic analyses, but could not identify the cause. To our knowledge, her clinical and pathological courses have never been described in the literature.

Determinants of outcomes following acute child encephalopathy and encephalitis: pivotal effect of early and delayed cooling.

BACKGROUND: Acute encephalopathy/encephalitis is one of the most important causatives of mortality and neurological deficit during childhood. The aim of this retrospective observational study was to investigate clinical variables and therapeutic options associated with the outcome of children with acute encephalopathy/encephalitis. METHODS: Relationships between the clinical information at admission and the neurological outcome evaluated using Pediatric Cerebral Performance Category Scale (PCPC) at 12 months after admission were assessed in 43 patients who were treated at 10 Japanese paediatric intensive care units. RESULTS: Sixteen patients were cared for at normothermia, whereas mild hypothermia was applied to 27 children. In univariate analysis, ages ≤ 18 months, marked elevation in serum lactate dehydrogenase (LD) and aspartate transaminase, diagnosis of either acute necrotising encephalopathy or haemorrhagic shock and encephalopathy syndrome and longer hypothermic periods were associated with increased risks of death or severe neurological deficit, whereas hypothermia showed pivotal effects: the outcome of children cooled after 12 h of diagnosis was statistically invariant with normothermic children, but was significantly worse compared with children cooled ≤ 12 h. In multivariate analysis, younger ages and elevated serum LD were associated with adverse outcomes, whereas early initiation of cooling was related to favourable outcomes. For normothermic children, PCPC scores were dependent on the computed tomographic findings suggestive of cerebral oedema, serum LD levels and Glasgow Coma Scale at admission. For hypothermic children, PCPC scores depended on longer delays in cooling initiation. CONCLUSION: Without therapeutic hypothermia, the outcome of children was determined by variables suggestive of the severity of encephalopathy/encephalitis at admission. Hypothermia may have pivotal impacts on the outcome of children according to the timing of cooling initiation following acute encephalopathy/encephalitis.