Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome : neuropathological and biochemical study of two cases

• Published in: Acta neuropathologica Vol. 97; no. 5; pp. 469 - 480
• Main Authors: RODRIGUEZ, D, GELOT, A, PHAM-DINH, D, DELLA GASPERA, B, ROBAIN, O, PONSOT, G, SARLIEVE, L. L, GHANDOUR, S, POMPIDOU, A, DAUTIGNY, A, AUBOURG, P
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.1999; Springer Nature B.V
• Subjects: Anterior commissure; Ataxia; Ataxia - pathology; Atrophy; Axons; Biological and medical sciences; Brain - pathology; Carbonic anhydrase II; Central nervous system; Cerebellum; Child; Children; Corpus callosum; Cytoplasm; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Glial cells; Glial fibrillary acidic protein; Humans; Leukodystrophy; Male; Medical sciences; Myelin basic protein; Myelin proteolipid protein; Myelin Sheath - pathology; Myelination; Neurology; Neuronal-glial interactions; Neuropathology; Oligodendrocyte-myelin glycoprotein; Oligodendrocytes; Oligodendroglia - pathology; Organ Size; Phosphodiesterase; Proteins; Substantia alba; Syndrome; Human; Nervous system diseases; Orthochromatic leukodystrophy; Exploration; Cerebral disorder; Case study; Pathology; Oligodendrocyte; Demyelination; Central nervous system disease; Ataxia; Degenerative disease; Neurological disorder; Child
• DOI: 10.1007/s004010051016
• ISSN: 0001-6322

We report neuropathological, biochemical and molecular studies on two patients with childhood ataxia with diffuse central nervous system hypomyelination (CACH) syndrome, a leukodystrophy recently defined according to clinical and radiological criteria. Both had severe cavitating orthochromatic leukodystrophy without atrophy, predominating in hemispheric white matter, whereas U-fibers, internal capsule, corpus callosum, anterior commissure and cerebellar white matter were relatively spared. The severity of white matter lesions contrasted with the rarity of myelin breakdown products and astroglial and microglial reactions. In the white matter, there was an increase in a homogeneous cell population with the morphological features of oligodendrocytes, in many instances presenting an abundant cytoplasm like myelination glia. These cells were negative for glial fibrillary acidic protein and antibodies PGM1 and MIB1. Some were positive for myelin basic protein, proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein, but the majority were positive for human 2'-3' cyclic nucleotide 3' phosphodiesterase and all were positive for carbonic anhydrase II, confirming that they are oligodendrocytes. Myelin protein and lipid content were reduced. The PLP gene, analyzed in one case, was not mutated or duplicated. The increased number of oligodendrocytes without mitotic activity suggests an intrinsic oligodendroglial defect or an abnormal interaction with axons or other glial cells. This neuropathological study supports the notion that CACH syndrome constitutes a specific entity.