Disorders of the cerebral white matter in children

Sammanfattning: The aims of this thesis were to describe the clinical spectrum in a large group of children characterised as having an abnormal magnetic resonance imaging (MRI) signal from cerebral white matter (WM) and to study the radiological, clinical and ophthalmological features in that subgroup where aetiology was unknown. We also wanted to look at biochemical markers in the cerebrospinal fluid (CSF) to elucidate pathological processes which were responsible for the WM abnormalities. A further aim was to identify useful diagnostic clues and to differentiate a progressive disease from non-progressive disorders.Methods: I. MRI and clinical data (medical records) from 100 children considered to have abnormal cerebral WM were assessed. II. Those 26 children with abnormal WM of unknown cause were studied in detail using clinical, radiological, ophthalmic and neurochemical methods. The ophthalmic examination included visual evoked potentials (VEP). The neurochemical investigations included analyses of CSF markers for myelin (sulfatide), gliosis (ganglioside GD3, glial fibrillary acid protein -GFAP), nerve cells (gangliosides), dendrites (ganglioside GD1b), axons (neurofilament - NFL, tau protein), synapses (gangliosides GM1 and GD1a) and neurotransmission (monoamines: 5-HIAA, HVA, HMPG) as well as seeking signs of infectious or inflammatory processes (protein quantitation -albumin, IgG, IgM- and oligoclonal bands). Results: I. Progressive diseases (for example leukodystrophies and other neurodegenerative disorders) were found in 45 % of the children, a relapsing-remitting course in 15 % (for example MS, ADEM and SLE) and non-progressive disorders (for example maldevelopment and sequel after insults) in 26%. In 14% the clinical course could not be categorised. In about 60 % of the children, the nature or cause of the disorder was unknown. II. The abnormal MRI signal could be classified as: generalised (involving all supratentorial WM) in 12 children; bilateral (symmetric but sparing parts of the WM) in 9 and asymmetric (focal or multifocal) in 5. Progressive disease was indicated by increasing MRI pathologic findings and infratentorial involvement, abnormal VEP, spasticity and positive heredity or by increased levels of NFL, tau protein and very high GFAP in the CSF. Increased GD3 and HVA were found in non-progressive disorders.Conclusions: There is great variability and heterogeneity of cause and manifestations for WM abnormalities in children. The disorders are characterised by signs and symptoms presenting early in life, most often in the form of psychomotor delay and hypotonia. Signs appearing later are spasticity, ataxia and severe motor and learning disabilities. Ophthalmic abnormalities predominate, most often in the form of visual impairment, optic nerve pathology and aberrant VEP. The neurochemical characteristics are signs of increased turnover of myelin, gliosis, neuroaxonal degeneration and disturbed nerve cell maturation and sustenance as well as impaired function of dopaminergic and serotonergic transmitter systems. This study found a combination of radiological, clinical, ophthalmological and neurochemical methods to be the most useful for diagnostic and prognostic purposes.

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