Alexanders Disease

Alexander's disease may be sporadic or familial. Autosomal dominant inheritance has been demonstrated in familial cases. Alexander disease is associated with mutations in the gene coding for glial fibrillary acidic protein (GFAP), an intermediate filament protein of astrocytes. In infants, the clinical course ranges from a few weeks to several years. Older infants develop mega-lencephaly. The juvenile form, with onset between 4 and

10 years, has a slower course. Bulbar symptoms and signs are characteristic clinical manifestations. The rare adult form may present with motor dysfunction, palatal myoclonus, and abnormal eye movements. No specific laboratory test is available for the disease. MRI is helpful in demonstrating the white matter changes and a peri-ventricular rim.

The pathology is characterized by bilateral widespread degeneration of myelin with frontal predominance and the presence of Rosenthal fibers. In infants, the myelin degeneration is extensive and may progress to cavitation. It is less severe in older children and adults. The arcuate fibers are preserved, and axonal damage is

figure 9.14

Alexander's disease. Rosenthal fibers are concentrated around a blood vessel and are also diffusely dispersed in the white matter (HE).

figure 9.14

Alexander's disease. Rosenthal fibers are concentrated around a blood vessel and are also diffusely dispersed in the white matter (HE).

variable. The Rosenthal fibers are the diagnostic hallmark of the disease (Fig. 9.14). These are eosinophilic, rod-shaped structures of astrocytic origin situated around blood vessels, beneath the pia mater, and along the ependymal lining of the ventricles. They contain GFAP and two heat shock proteins (hsp)—a B-crystalline and hsp27.

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