CEREBROSPINAL-FLUID INVESTIGATIONS FOR NEUROMETABOLIC DISORDERS

Careful clinical delineation and advances in analytical methods have o pened new possibilities for the detection of inherited neurometabolic disorders, some of which require specific CSF analyses for diagnosis. Although patients suffering from these disorders have recognizable phe notypes, there are strong indications that remain many undiagnosed, le ading to a continuation of futile diagnostic searches and, for most di sorders, withholding of available rational therapy. As there is still widespread uncertainty about when to perform specialist CSF investigat ions, it is the aim of this paper to define the place for CSF investig ations in the diagnostic work-up of a child with an encephalopathy of unknown origin. Most neurometabolic disorders can be identified throug h serum, plasma and urine analyses in conjunction with neuroradiologic al investigations. Whenever CSF investigations are performed, the anal ysis should include quantitative determination of lactate, pyruvate an d amino acids, the latter by methods especially suited for CSF, in add ition to cells, glucose, protein, immunoglobulin classes, specific imm unoglobulins, and an evaluation of the blood-brain barrier. If the dis ease course is non-progressive or if extracerebral symptoms are presen t in addition to an encephalopathy, e.g. endocrinological, hepatic, mu scular or renal symptoms, investigations of metabolites in CSF over an d above lactate, pyruvate and amino acids are generally noncontributar y. Specific CSF investigations, which are discussed in detail, test me tabolic pathways of brain metabolism, especially of neurotransmission. For a successful diagnosis of these defects, analyses must be planned individually, before CSF samples are taken, based on family history, clinical findings and disease course. Different determinations require different logistics from taking of the sample to shipment. One indica tion for specialized CSF analyses including biogenic monoamines and GA BA is severe neonatal/infantile epileptic encephalopathy. In addition to a therapeutic trial of Bs, folinic acid should be tried empirically for two to three days as the emerging syndrome of folinic acid respon sive seizures appears to be the underlying cause in a sizable proporti on of patients. In later infancy and childhood, defects in the metabol ism of the biogenic monoamines may be suspected in patients with (fluc tuating) extrapyramidal disorders, in particular Parkinsonism dystonia or more general ''athetoid cerebral palsy'', and vegetative disturban ces. A severe epileptic encephalopathy and progressive mental retardat ion may be present. Neuroimaging findings do not show specific lesions . Determinations of folates and organic acids in CSF appear at present only warrantable individually in special constellations, e.g. classic al clinical findings and disease course suggestive of glutaryl-CoA deh ydrogenase deficiency with repeated negative quantitative analyses of organic acids in urine. The diagnosis of disorders, which require spec ific analyses of CSF, can only be achieved by conscious diagnostic dec isions based on a concept of the respective disease and repeated scrup olous expert clinical evaluation aided by an array of investigations i n blood and urine as well as neuroimaging findings. No single one inve stigation in CSF can serve as a ''selective screening'' test. A growin g awareness of these disorders is needed and should lead to increased and earlier diagnosis of patients through fewer rather than more lumba r punctures.