Alexander's disease: case report including histopathological and electron microscopic features.

Abstract

SUMMARY We report a case of Alexander's disease in a black South African boy of 9 years. The child presented with a grossly abnormal stooped posture, generalised weakness, and slurred nasal speech. Computerised tomography revealed diffuse low radio-density confined to the white matter, and enlarged ventricles. Cerebral biopsy confirmed the diagnosis. The histopathological and electron microscopic features are essentially the same as those described in previous reports. We note the presence of dense clumps of material within some of the Rosenthal fibres, and can find no reference in the literature describing this. Sural nerve biopsy was normal.Case report A black South African boy child aged 9 years and 5 months was first seen at Baragwanath Hospital in July 1978. A rather inadequate history was supplied by his sister. His main complaints were difficulty in walking because of painful knees and backache, and generalised weakness for approximately one month. The patient has six healthy siblings, and his own birth and milestones were apparently normal. From the clinical appearance of the child we considered that he had been ill for longer than the history indicated.He was a thin black male child with a head circumference of 570 mm. He had a strikingly abnormal stooped posture, with flexion of the neck, drooping of the shoulders, and flexion of both hip and knee joints (Fig. 1)

Biopsy Diagnosis of Familial Alexander’s Disease

“…6]. CT findings include marked dilatation of the lateral and third ventricles, and diffuse, symmetrical, low density of the white matter, particularly in the frontal lobes [5,11 ]. One case has been reported to have a normal CT scan [ 12], The adult form of Alexander's disease may be divided into two categories, the first of which has a waxing and waning course indistinguishable from multiple sclerosis.…”

“…Rosenthal fibers are found throughout the central nervous system and are especially concentrated in the subpial, subependymal and perivascular regions. This is associated with gliosis, exten sive myelin disintegration and a notable lack of phagocy tosis [5,6].…”

Cerebral proton magnetic resonance spectroscopy in infantile Alexander disease

“…The morphological hallmark is the presence of large numbers of Rosenthal fibres predominantly in the subpial, subependymal and perivascular regions of the central nervous system [10,11,15,19]. In his original report Alexander stressed the presence of "rod-shaped, rounded or nummular .…”

Infantile Alexander Disease: AGFAPMutation in Monozygotic Twins and Novel Mutations in Two Other Patients

“…Neuropathological examination reveals megalencephaly, demyelination, degeneration of astrocytes, and, as the diagnostic hallmark, the presence of countless Rosenthal fibers throughout the brain [4,5,7]. Rosenthal fibers are cytoplasmatic inclusions containing glial acidic fibrillary protein (GFAP) and small heat-shock proteins [6,8].…”