Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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February 10, 2022
Alexander Disease Type I
- Background:
- Alexander disease type I is a rare astrogliopathy related to a genetic mutation in the GFAP gene that is usually de novo but can be inherited in an autosomal dominant pattern.
- It manifests before the age of 4 and is characterized by degeneration of the white matter in the central nervous system.
- The prognosis is poor, but with supportive therapies, some patients can reach adolescence and adulthood.
- Clinical Presentation:
- Patients with type I Alexander tend to present with early age at onset (often before 4 years), seizures, encephalopathy, paroxysmal deterioration, failure to thrive, developmental delay, and hallmark radiologic features.
- Key Diagnostic Features:
- Five MRI-based criteria for diagnosis of typical Alexander disease have been described and are most commonly seen in type I:
- 1. frontal predominance of central white matter involvement manifested by T2 hyperintensity and T1 hypointensity;
- 2. a periventricular rim of T2 hypointensity and T1 hyperintensity;
- 3. abnormal T2 signal, swelling or atrophy of basal ganglia/thalamus;
- 4. abnormal T2 signal of the brainstem;
- 5. and contrast enhancement of selected structures (in this case, contrast was not administered).
- These diagnostic criteria help prompt GFAP sequencing analysis to confirm the diagnosis.
- MR spectroscopy of the affected white matter is characterized by decreased NAA and elevated Cho, myoinositol, and lactate.
- Five MRI-based criteria for diagnosis of typical Alexander disease have been described and are most commonly seen in type I:
- Differential Diagnoses:
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Glutaryl-CoA dehydrogenase deficiency is characterized by the bilateral widening of the Sylvian fissures associated with hypoopercularization, resulting in the “bat-wing” appearance.
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The absence of cerebral calcifications and atrophy excludes Aicardi-Goutières syndrome.
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Megalocephalic leukoencephalopathy with subcortical cysts is characterized by the presence of subcortical cysts, which are typically identified in the anterior temporal lobes and less frequently in the frontal, parietal, or occipital lobes.
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In Canavan disease, the white matter involvement is typically diffuse, bilateral, and involving the subcortical U-fibers. MR spectroscopy is marked by a high NAA and NAA/Cr ratio.
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In the frontal variant of adrenoleukodystrophy, brainstem, cerebellar, and spinal cord involvement are not common.
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Treatment:
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Treatment is symptomatic and focuses on controlling seizures, maintaining lung function, and nutrition.
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