OBJECTIVES—To examine the CSF concentrations of molecules reflecting demyelination, neuronal and axonal degeneration, gliosis, monoaminergic neuronal function, and aminergic and peptidergic neurotransmission in a large series of patients with normal pressure hydrocephalus (NPH) or subcortical arteriosclerotic encephalopathy (SAE), to elucidate pathogenic, diagnostic, and prognostic features. METHODS—CSF concentrations of glycosphingolipid (sulfatide), proteins (neurofilament triplet protein (NFL), glial fibrillary acidic protein (GFAP)), neuropeptides (vasoactive intestinal peptide (VIP), 4-aminobutyric acid (GABA)), and monoamines (homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG)) were analysed in 43 patients with NPH and 19 patients with SAE. The diagnoses of NPH and SAE were based on strict criteria and patients with NPH were subsequently operated on. Twelve clinical variables, psychometric tests measuring perceptual speed, accuracy, learning, and memory and a psychiatric evaluation were performed in all patients and before and after a shunt operation in patients with NPH. RESULTS—The CSFsulfatide concentration was markedly increased in patients with SAE(mean 766, range 300-3800 nmol/l) compared with patients with NPH(mean 206, range 50-400 nmol/l) (p<0.001). 5-HIAA, GABA, and VIP inCSF were higher in patients with SAE than in patients with NPH. Thepatients with NPH with cerebrovascular aetiology had higher sulfatideconcentrations and a poorer outcome after shunt surgery than patientswith NPH with other aetiologies. CONCLUSIONS—Thepathogenesis of the white matter changes in NPH and SAE is differentand ischaemic white matter changes can be a part of the NPH state. Themarkedly increased CSF sulfatide concentrations in patients with SAEindicate ongoing demyelination as an important pathophysiologicalfeature of SAE. The CSF sulfatide concentration distinguished betweenpatients with SAE and those with NPH with a sensitivity of 74% and aspecificity of 94%, making it an important diagnostic marker.
