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Updated: Aug 16, 2026

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Detection of Central Nervous System Pathogens
Published on: April 17, 2026
[Diagnosis in cerebrospinal fluid: possible applications in neurological practice]
M M Verbeek1, M A A P Willemsen, B R Bloem
1Afd. Neurologie, Universitair Medisch Centrum St Radboud, Postbus 9101, 6500 HB Nijmegen. m.verbeek@cukz.umcn.nl
Abstract:
Examination of the cerebrospinal fluid (CSF) is part of the modern diagnostics of many neurological diseases. When an acute or chronic meningitis or encephalitis is suspected, the distinction between an acute viral and a bacterial intrathecal infection can generally be rapidly made via examination of the CSF. In case of a chronic infection this will determine the direction of further microbiological analysis. When there are clinical indications for subarachnoid haemorrhage but no abnormalities on the CT-scan, it can be either demonstrated or excluded by means of spectrophotometric analysis of blood pigments in the CSF. In case of possible multiple sclerosis (MS) and contraindications for MRI, or if the combination of the clinical symptoms and MRI does not yield a definitive diagnosis, then the demonstration of unique oligoclonal IgG-bands in the CSF is an important parameter in confirming a diagnosis of 'MS'. In practice, metastases to the leptomeninges are often detected by means of (repeated) cytopathological analysis of the CSF, which has a higher sensitivity and specificity than MRI. Examination of the CSF also plays an important role in the diagnosis of (hereditary) metabolic encephalopathies in childhood. In case of watery discharge from the nose or ear following trauma or neurosurgery, it can be determined whether or not this is leaking CSF. Analysis of certain brain-specific proteins in the CSF can contribute to the differential diagnosis of dementia syndromes. The added diagnostic value of examination of the CSF in hypokinetic rigidity syndromes is still unclear. The complications of a spinal puncture often remain limited to post-puncture headache. Contraindications include intracranial space-occupying abnormalities, compression of the spinal cord, haemorrhagic diathesis and abnormalities around the puncture site.
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