Alexander Disease - Classification Revisited and Isolation of a Neonatal Form

Alexander disease is usually classified according to the age of onset, e.g. an infantile form with onset during the first two years of life, a juvenile form with onset in childhood, mainly school age. It has been recognized, however, that the clinical course can be very variable within these groups. Thus, this clinical classification is not a useful predictor of severity and progression of the disease.

This is demonstrated here on the basis of the history of seven own patients and a literature review.

Only an onset in very early infancy, during the neonatal period, seemed to be associated with a rather uniform pattern of disease course, often leading to early death. This neonatal form showed very stereotyped symptoms, in part different from later onset: Early, often intractable, generalized seizures; hydrocephalus with raised intracranial pressure due to aqueductal stenosis because of pathological astroglia proliferation; lack of developmental progression but without prominent spasticity or ataxia; elevated CSF protein content. This was associated with the well-established neuroradiological findings, e.g. severe white matter affection with fronto-temporal predominance, involvement of basal ganglia and periventricular enhancement as an obligatory symptom. The identification of this early onset form is especially important as seizures and signs of raised intracranial pressure may mislead the diagnosis.

Key words

Alexander disease - Neonatal onset - Magnetic resonance imaging - Hydrocephalus

References

• 1 Alexander W. Progressive fibrinoid degeneration of fibrillary astrocytes with mental retardation in a hydrocephalic infant.  Brain. 1949;  72 373-381
• 2 Arend A O, Leary P M, Rutherford G S. Alexander's disease: a case report with brain biopsy, ultrasound, CT scan and MRI findings.  Clin Neuropathol. 1991;  10(3) 122-126
• 3 Borrett D, Becker L E. Alexander's disease: a disease of astrocytes.  Brain. 1985;  108 367-385
• 5 Duckett S, Schwartzman R J, Osterholm J, Rorke L B, Friedman D, McLellan T L. Biopsy diagnosis of familial Alexander's disease.  Pediatr Neurosurg. 1992;  18 134-138
• 6 Farell K, Chuang S, Becker L E. Computed tomography in Alexander's disease.  Ann Neurol. 1984;  15(6) 605-607
• 7 Garcia L, Gascon G, Ozand P, Yaish H. Increased intracranial pressure in Alexander disease: a rare presentation of white-matter disease.  J Child Neurol. 1992;  7 168-171
• 8 Garret R, Ames R P. Alexander disease: case report with electron microscopical studies and review of the literature.  Arch Pathol. 1974;  98 379-385
• 9 Grodd W, Krägeloh-Mann I, Klose U, Sauter R. Metabolic and destructive brain disorders in children: findings with localized proton MR spectroscopy.  Radiology. 1991;  181 173-181
• 10 Head M W, Corbin E, Goldman J E. Overexpression and abnormal modification of the stress proteins α B-crystallin and HSP27 in Alexander disease.  Am J Pathol. 1993;  143(6) 1743-1753
• 11 Hess D C, Fischer A Q, Yaghmai F, Figueroa R, Akamatsu Y. Comparative neuroimaging with pathologic correlates in Alexander disease.  J Child Neurol. 1990;  5 248-252
• 12 Holland I M, Kendall B E. Computed tomography in Alexander's disease.  Neuroradiology. 1980;  20 103-106
• 13 Nagao H, Kida K, Matsuda H, Shishido T, Matsuoka K. Alexander disease: clinical, electrodiagnostic and radiographic studies.  Neuropediatrics. 1981;  12(1) 22-32
• 14 Neal J W, Cave E M, Singhrao S K, Cole G, Wallace S J. Alexander's disease in infancy and childhood: a report of two cases.  Acta Neuropathol. 1992;  84 322-327
• 15 Peiffer J. Alexander's disease - really a leucodystrophy?.  Pathol Eur. 1968;  3 305-312
• 16 Peiffer J. Differentiation of various types of leukodystrophy.  World Neurol. 1962;  3 580-601
• 17 Pridmore C L, Baraitser M, Harding B, Boyd S G, Kendall B, Brett E M. Alexander's disease: clues to diagnosis.  J Child Neurol. 1993;  8 134-144
• 18 Richardson E P. Alexander Disease. Owen GH Recent Advances in Degenerative Diseases of the Central Nervous System in Infants and Children (Report of the 42nd Ross Conference on Pediatric Research). Columbus (Ohio); Ross Laboratories 1963: 50-58
• 19 Russo L S, Aron A, Anderson P J. Alexander's disease: a report and reappraisal.  Neurology. 1976;  26 607-614
• 20 Schochet S S, Lampert P W, Earle K M. Alexander's disease: a case report with electron microscopic observations.  Neurology. 1968;  18 543-549
• 21 Schuster V, Horwitz A E, Kreth H W. Alexander's disease: cranial MRI and ultrasound findings.  Pediatr Radiol. 1991;  21 133-134
• 22 Shah M, Ross J S. Infantile Alexander disease: MR appearance of a biopsy-proved case.  Am J Neuroradiol. 1990;  11 1105-1106
• 23 Shinghal B S, Gursahani R D, Udani V P, Biniwale A A. Megalencephalic leukodystrophy in an Asian Indian ethnic group.  Pediatr Neurol. 1996;  14 291-296
• 24 Townsend J J, Wilson J F, Harris T, Coulter D, Fife R. Alexander's disease.  Acta Neuropathol. 1985;  67 163-166
• 25 Trommer B L, Naidich T P, Dal Canto M C, McLone D G, Larsen M B. Noninvasive CT diagnosis of infantile Alexander disease: pathologic correlation.  J Comput Assisted Tomography. 1983;  7(3) 509-516
• 26 van der Knaap M S, Barth P G, Stroink H. Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children.  Ann Neurol. 1995;  37 324-334
• 27 van der Knaap M S, Valk J. Alexander's disease. van der Knaap MS, Valk J Magnetic Resonance of Myelin, Myelination and Myelin Disorders. Berlin, Heidelberg, New York; Springer 1995: 259-264
• 28 van der Knaap M S, Breiter S T, Naidu S, Hart A AM, Valk J. Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach.  Radiology. 1999;  213 121-133