Epilepsy in Aicardi-Goutières syndrome

Eur J Paediatr Neurol. 2014 Jan;18(1):30-7. doi: 10.1016/j.ejpn.2013.07.005. Epub 2013 Sep 5.


Background: Aicardi-Goutières syndrome (AGS) is a genetically determined early-onset encephalopathy with variable phenotype, including neurologic manifestations such as dystonia, spasticity, epileptic seizures, progressive microcephaly, and severe developmental delay. The aim of our study was the characterization of epilepsy, one of the most frequent and severe AGS manifestations, in molecularly confirmed patients.

Methods: We reviewed the medical records, EEG, and CT/MRI findings in 16 patients aged 1-22 years that carried AGS1-5 mutations.

Results: Epilepsy manifested in 12 (75%) patients and took a refractory course in 9 (56%). 4 (25%) patients presented with seizures in the first four weeks and 11 (69%) altogether in the first year of life. Spasms were reported in 3 (19%) patients, focal seizures in 4 (25%), myoclonic in 5 (31%), symmetric or asymmetric tonic in 11 (69%), generalized tonic-clonic in 3 (19%) and status epilepticus in 4 (25%). EEG recordings initially showed a slow and disorganized background, followed by a regional intermittent theta/delta slow, while obvious multifocal or generalized epileptic discharges were only observed at follow-up. None of these EEG features were specific of AGS. There was no discernible correlation between the genotype and epilepsy onset, seizure types and epilepsy evolution. Epilepsy severity did not correspond to neuroimaging pathology.

Discussion: Epilepsy constitutes a cardinal feature of AGS, characterized by early onset, predominantly tonic semiology and a refractory course. The early discrimination of epileptic seizures from paroxysmal dystonia poses a challenge for neuropaediatricians, considering the initially inconspicuous or non-specific EEG findings. This study underlines the necessity of a more systematic serial evaluation of AGS patients using long-term video-EEG recordings.

Keywords: Aicardi–Goutières syndrome; Dystonia; Epilepsy; Leukoencephalopathy; Spasms; Status epilepticus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoimmune Diseases of the Nervous System / complications
  • Autoimmune Diseases of the Nervous System / genetics
  • Autoimmune Diseases of the Nervous System / physiopathology*
  • Child
  • Child, Preschool
  • Epilepsy / etiology
  • Epilepsy / genetics
  • Epilepsy / physiopathology*
  • Follow-Up Studies
  • Humans
  • Infant
  • Nervous System Malformations / complications
  • Nervous System Malformations / genetics
  • Nervous System Malformations / physiopathology*
  • Phenotype
  • Retrospective Studies
  • Severity of Illness Index
  • Young Adult

Supplementary concepts

  • Aicardi-Goutieres syndrome