Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Wolf
Nicole I
NI
Pediatric Neurology, University Children's Hospital, Heidelberg, Germany. n.wolf@vumc.nl
Rahman
Shamima
S
Schmitt
Bernhard
B
Taanman
Jan-Willem
JW
Duncan
Andrew J
AJ
Harting
Inga
I
Wohlrab
Gabriele
G
Ebinger
Friedrich
F
Rating
Dietz
D
Bast
Thomas
T
D002648:Child; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D013226:Status Epilepticus / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D014316:Tritium
D014316:Tritium; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human