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Aicardi-Goutières syndrome: an update and results of interferon-alpha studies
F Goutières1, J Aicardi, P G Barth
1Neuropediatric Unit, Hôpital des Enfants Malades, Paris, France.
Insights
Aicardi-Goutières syndrome, a familial encephalopathy, presents with basal ganglia calcification and chronic cerebrospinal fluid (CSF) lymphocytosis. High interferon-alpha levels suggest a role in this progressive neurodegenerative disorder.
Area of Science:
- Neurology
- Genetics
- Immunology
Background:
- Aicardi-Goutières syndrome is a rare genetic disorder characterized by encephalopathy, basal ganglia calcification, and chronic cerebrospinal fluid (CSF) lymphocytosis.
- The syndrome's clinical presentation and progression can vary significantly among affected individuals.
Purpose of the Study:
- To review clinical, imaging, and laboratory findings in patients with Aicardi-Goutières syndrome.
- To investigate the role of interferon-alpha in the pathogenesis of the disorder.
- To support the autosomal recessive inheritance pattern of Aicardi-Goutières syndrome.
Main Methods:
- Retrospective review of 27 patients with Aicardi-Goutières syndrome.
- Analysis of neuroimaging (brain atrophy, calcification), CSF analysis (lymphocytosis), and serum/CSF interferon-alpha levels.
- Neuropathological examination in two patients.
Main Results:
- Early onset (within 4 months) and microcephaly were common in pediatric patients.
- All patients exhibited severe, progressive brain atrophy; calcification patterns varied.
- Persistent CSF lymphocytosis and elevated serum/CSF interferon-alpha levels were observed in a significant proportion of patients, suggesting intrathecal synthesis.
- Profound disability was noted in surviving patients, though severity varied.
Conclusions:
- Aicardi-Goutières syndrome is a severe neurodegenerative disorder with autosomal recessive inheritance.
- Elevated interferon-alpha levels are a key feature and may contribute to the disease's pathogenesis.
- Despite variable presentation, the syndrome leads to significant neurological impairment.
Abstract:
Twenty-seven patients with familial encephalopathy with calcification of the basal ganglia and chronic cerebrospinal fluid (CSF) lymphocytosis (Aicardi-Goutières syndrome) are reviewed. In 19 children, the onset was within the first 4 months of life. Most patients had normal head circumference at birth, but 21 developed microcephaly between 3 and 12 months. Neuroimaging showed severe and progressive brain atrophy in all patients. The extent and intensity of the calcification was variable even in the same sibship. CSF lymphocytosis persisted beyond 12 months of age in 7 children. High levels of interferon-alpha were found in serum and CSF in 14 patients. The higher CSF levels suggest intrathecal synthesis. Tubuloreticular inclusions related to the presence of interferon were found in 4 additional children. The 19 patients still alive (6 older than 10 years) are profoundly disabled. However, the syndrome may present with individual variations in severity, rapidity of evolution, and imaging features. Neuropathological examination in 2 patients failed to detect significant inflammatory lesions and showed only foci of necrosis and wide-spread demyelination. This study supports an autosomal recessive inheritance for this syndrome. The high level of interferon-alpha is not explained but may play a role in the pathogenesis of the disorder.