Aicardi-Goutières Syndrome

Aicardi-Goutières Syndrome (Leukodystrophy with calcification of the basal ganglia and lymphocytosis of cerebrospinal fluid): This is a severe, early onset encephalopathy with characteristic calcification in the basal nuclei and chronic lymphocytosis in the CSF. This syndrome has many superficial similarites to congenital infection and, although rare, should be differentiated from congenital infections. The salient features are calcification of the basal ganglia and lymphocytosis of the CSF with elevated interferon-alpha level.

Genetics: This is an autosomal-recessive disorder.

Clinical fetures: There is early onset in the 1st year of life, progressive course with acquired microcephaly, progressive cerebral motor dysfunction (spasticity, dystonia). Abnormal eye movements with visual inattention are typically present by 3 months of age. Aicardi-Goutières syndrome is usually fatal or causes persistent vegetative state from early childhood. The motality during the first year of live is about 25%.

CSF: There is a peculiar type of chronic CSF lymphocytosis (10-80 cells/mm³) without evidence of infection, elevated interferon-alpha (INF-alpha) in CSF, a major characteristic of this syndrome. Repeated spinal tapping may be necessary to rule out infection.

Imaging discloses calcification of the basal ganglia, possibly the thalamus and, occasionally, cerebellum on imaging.

Pathology include extensive white matter disease; symmetric calcification of white matter, basal ganglia, thalami and dentate nuclei; and vasculopathy. Extensive loss of myelin has been described in some autopsy cases. Small infarction has also been described. Strictly speaking, this is a neurodegenerative disease with leukodystrophy. [Aicardi J and Goutieres F, 1986], [van der Knaap MS et al., 1995], [Barth PG et al., 1999] [Goutieres F et al., 1998]