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Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features
Nicole I Wolf1, Shamima Rahman, Bernhard Schmitt
1Pediatric Neurology, University Children's Hospital, Heidelberg, Germany. n.wolf@vumc.nl
Insights
Alpers' disease, caused by POLG1 mutations, can present as refractory convulsive status epilepticus in children. A specific EEG pattern (RHADS) aids early diagnosis, preventing dangerous valproic acid use and guiding management.
Area of Science:
- Pediatric Neurology
- Neurogenetics
- Epileptology
Background:
- Refractory convulsive status epilepticus (RCSE) in children is a rare medical emergency.
- Metabolic disorders, particularly Alpers' disease due to POLG1 mutations, are significant underlying causes.
- Status epilepticus can be the initial clinical manifestation of Alpers' disease.
Purpose of the Study:
- To highlight Alpers' disease as a critical differential diagnosis in pediatric RCSE.
- To emphasize the diagnostic utility of a specific EEG signature for Alpers' disease.
- To underscore the importance of avoiding valproic acid in patients with Alpers' disease due to the risk of fatal hepatotoxicity.
Main Methods:
- Case series of five pediatric patients diagnosed with Alpers' disease.
- Clinical presentation, seizure semiology, EEG findings, and neuroimaging (MRI) were analyzed.
- Review of treatment outcomes, including the use of valproic acid and liver transplantation.
Main Results:
- All five patients presented with RCSE as the first symptom.
- Four patients exhibited unilateral occipital rhythmic high-amplitude delta with superimposed (poly)spikes (RHADS) on EEG.
- MRI showed cortical and thalamic involvement in all patients; three had normal metabolic investigations.
- Three patients died within 3-12 months; two experienced fatal liver failure linked to valproic acid treatment.
Conclusions:
- Alpers' disease should be considered in the differential diagnosis of childhood RCSE.
- The EEG pattern RHADS is a key diagnostic marker for Alpers' disease.
- Timely diagnosis based on EEG findings is crucial for appropriate management, including avoiding contraindicated medications like valproic acid.
Purpose:
Refractory convulsive status epilepticus in infancy and childhood is a rare emergency situation. Metabolic disorders frequently underlie this condition, in particular Alpers' disease caused by POLG1 mutations. Status epilepticus may be the first symptom. A pathognomonic electroencephalography (EEG) signature may facilitate diagnosis of Alpers' disease and allow timely avoidance of valproic acid, which is contraindicated in this disorder because it may trigger fatal liver failure.
Patients:
We present five patients with Alpers' disease caused by mutations in POLG1. Age of onset ranged from 7 months to 10 years. Three of the five children died after 3 to 12 months after onset of status epilepticus. Two of these had liver failure associated with use of valproic acid; liver transplantation in one child did not prevent a fatal neurologic outcome.
Results:
Convulsive status epilepticus was the first obvious sign of Alpers' disease in all children. All had focal clonic and complex-focal seizures; four of them developed epilepsia partialis continua. In four children, initial EEG showed unilateral occipital rhythmic high-amplitude delta with superimposed (poly)spikes (RHADS). Magnetic resonance imaging (MRI) revealed cortical and thalamic involvement in all, although there were only discrete abnormalities in one child. Metabolic investigations remained normal in three children.
Conclusion:
Alpers' disease is an important differential diagnosis in childhood refractory convulsive status epilepticus. Its EEG hallmark of RHADS is important for timely diagnosis, management, and counseling.
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