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| Year : 1999 | Volume
: 47
| Issue : 4 | Page : 333-5 |
Alexander's disease : a case report of a biopsy proven case.
Tatke M, Sharma A
Department of Pathology, G.B. Pant Hospital, New Delhi, 110002, India.
Correspondence Address:
Department of Pathology, G.B. Pant Hospital, New Delhi, 110002, India.
A case of infantile onset Alexander's disease in a two and a half year old male child is presented, who had progressively increasing macrencephaly since birth. A frontal lobe biopsy revealed collections of Rosenthal fibres in the subpial and perivascular areas with diffuse dysmyelination and presence of reactive astrocytes. The Rosenthal fibres were immunoreactive for glial fibrillary acidic protein and ubiquitin. Electron microscopic examination showed the Rosenthal fibres as intra-astrocytic and extracellular granular osmiphilic collections.
How to cite this article:
Tatke M, Sharma A. Alexander's disease : a case report of a biopsy proven case. Neurol India 1999;47:333 |
Alexander's disease (or leucodystrophy) is characterised by macrencephaly, frequently associated with hydrocephalus, extensive proliferation of reactive astrocytes and formation of Rosenthal fibres by these cells, which are seen intracellularly and extracellularly, predominantly in the perivascular, subependymal and subpial regions. The presentation may be in the infantile, juvenile or adult forms.[1] The exact incidence of this disease in India is not known as there is no indexed report in English literature. None of the clinical or neurological findings is pathognomonic and the radiological picture is not diagnostic in all cases. However, a combination of findings may suggest the diagnosis and warrant histological confirmation. Less than fifty histologically proven cases have been reported in the world literature.[2],[3],[4],[5],[6] However, there is no documented case from India.
A two and a half year old male child was brought to the hospital for progressively increasing head size and developmental delay. The child was the first issue of a nonconsanguinous marriage, who was born full term. There was progressive increase in head size since birth and milestones were delayed. At admission the child was fully conscious, was able to recognise the mother, and there was no motor deficit. His fundus examination did not show any abnormality. Head circumference was 53 cm. CT and MRI scans of the brain revealed leucodystrophic dysmyelination associated with pachygyria (Figures. 1 and 2). The ventricular and cisternal system were normal. Biopsy from the frontal lobe was taken through right frontal craniotomy. The biopsy included cortex and white matter which were well demarcated. Microscopy revealed subpial gliosis and collections of Rosenthal fibres and reactive astrocytes in the cortex. There was diffuse loss of myelin demonstrated by luxol fast blue and Loyez's stains in the white matter with collections of Rosenthal fibres all over, more so in the perivascular and subpial regions [Figure. 3]. The Rosenthal fibres were immunoreactive with antibodies to GFAP [Figure. 4] and ubiquitin [Figure. 5] done by the peroxidase antiperoxidase technique. Ultrastuctural examination of this biopsy showed the Rosenthal fibres as extracellular osmiphilic granular deposits of varying sizes. A few astrocytes showed small intracellular deposits pushing the intermediate filaments to the periphery. All these features lead to the diagnosis of Alexander's disease.
Alexander's disease is a rare progressive neurological disorder seen over a wide age range.[1] The histopathological findings in this condition are distinctive to make a definite diagnosis. These include diffuse paucity of myelin with marked proliferation of astrocytes bearing Rosenthal fibres, the latter seen predominantly in the subpial, perivascular and subependymal areas. Rosenthal fibres are now known to be composed of GFAP and alpha-beta crystallin,[7] part of which is ubiquitinated. These are regarded as stress proteins which are induced in response to stress stimuli.[8] The formation of Rosenthal fibres is obviously preceeded by proliferation of pathologically altered astrocytes. The functional deficits of these astrocytes presumably contribute to insufficient myelination of the developing brain,[1],[5] since there are gap junctions between astrocytes and oligodendrocytic cell bodies or processes which provide a means of metabolic transport, and this is probably a prerequisite for the acquisition and maintenance of the myelin sheath.
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