General description

Alexander disease is a rare neurodegenerative disorder caused by mutations in the glial fibrillary acidic protein (GFAP) gene, leading to the formation of Rosenthal fibers composed of GFAP, αB-crystallin, and heat shock proteins in astrocytes. The disease is classified into three clinical types: infantile, juvenile, and adult, based on the age of onset and clinical progression.

Alexander disease is primarily caused by GFAP gene mutations, with 97% of cases showing these mutations. The accumulation of abnormal GFAP aggregates is believed to be a key factor in the disease's pathology, affecting astrocyte function by inhibiting molecular chaperones and proteasome function.

Infantile Alexander disease presents with a characteristic triad of clinical features that distinguish it from later-onset forms. The primary manifestations include seizures, macrocephaly, and psychomotor developmental delay. Seizures typically represent the most prominent and problematic symptom, often proving refractory to conventional antiepileptic therapy and significantly impacting both functional and life prognosis. Most cases have poor outcomes, with many patients dying by the age of 10.

The definitive diagnosis of Alexander disease is made by detecting Rosenthal fibers in brain tissue. Elevated levels of αB-crystallin and heat shock proteins in the cerebrospinal fluid further support the diagnosis, as these are components of the Rosenthal fibers.

Radiographic features

In MRI, Alexander disease is diagnosed based on the presence of four of five typical imaging findings:

1. High signal intensity on T2-weighted images in the cerebral white matter, predominantly in the frontal regions.
2. A periventricular rim, which appears as high attenuation on CT and shows signal shortening on both T1- and T2-weighted images.
3. Swelling or high signal intensity on T2-weighted images in the basal ganglia and thalamus.
4. High signal intensity on T2-weighted images particularly affecting the midbrain and medulla.
5. Abnormal contrast enhancement in areas such as the periventricular region, frontal lobe white matter, optic chiasm, fornix, basal ganglia, thalamus, dentate nucleus, or brainstem.

References

1. van der Knaap, Marjo S., et al. "Alexander disease: diagnosis with MR imaging." American Journal of Neuroradiology 22.3 (2001): 541-552.