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Published on: May 16, 2019
A case of severe progressive early-onset epileptic encephalopathy: unique GABAergic interneuron distribution and
1Department of Child Neurology, Osaka City General Hospital, Osaka, Japan.
Insights
This study details a unique case of early-onset epileptic encephalopathy in a young girl, characterized by novel EEG patterns and progressive brain atrophy. Despite extensive investigation, the exact cause remains unidentified, highlighting a rare and severe neurological disorder.
Area of Science:
- Neurology
- Pathology
- Genetics
Background:
- Early-onset epileptic encephalopathies are severe neurological disorders affecting infants.
- This study focuses on a unique case of early-onset epileptic encephalopathy with a suppression-burst pattern.
Observation:
- A 28-month-old girl presented with intractable epilepsy and a unique, age-dependent suppression-burst electroencephalography (EEG) pattern.
- Clinical observations included lack of developmental milestones, progressive cerebral atrophy on MRI, and cortical hypoperfusion on SPECT, suggesting GABA-A receptor dysfunction.
- Neuropathology revealed severe cerebral edema and atrophy, with an imbalanced distribution of GABAergic interneurons.
Findings:
- Despite comprehensive metabolic, pathological, and genetic analyses, the specific etiology of this severe early-onset epileptic encephalopathy could not be determined.
- The clinicopathological features presented were novel and not previously described in medical literature.
- The case showed similarities to focal cortical dysplasia and X-linked lissencephaly, but without identified mutations.
Implications:
- This case expands the understanding of the diverse clinical and pathological spectrum of early-onset epileptic encephalopathies.
- The findings underscore the need for further research into the underlying mechanisms of unexplained severe infant epilepsies.
- Highlights the potential for novel genetic or metabolic pathways contributing to these devastating conditions.
Abstract:
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.
