title: Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features.
abstract: 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.
authors.affiliation: Pediatric Neurology, University Children's Hospital, Heidelberg, Germany. n.wolf@vumc.nl
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmitt
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Taanman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Duncan
authors.forename: Inga
authors.initials: I
authors.lastname: Harting
authors.forename: Gabriele
authors.initials: G
authors.lastname: Wohlrab
authors.forename: Friedrich
authors.initials: F
authors.lastname: Ebinger
authors.forename: Dietz
authors.initials: D
authors.lastname: Rating
authors.forename: Thomas
authors.initials: T
authors.lastname: Bast
mesh_terms: 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
chemical_list: D014316:Tritium; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human