S1 Guideline “Lumbar Puncture and Cerebrospinal Fluid Diagnostics” Revised

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Under the leadership of Hayrettin Tumani (Ulm) and PD Dr. Hela-F. Petereit (Cologne), the guideline of the German Society for Neurology was revised in collaboration with the German Society for Clinical Neurochemistry and CSF Diagnostics and with the participation of the Austrian Society of Neurology (ÖGN) and the Swiss Neurological Society (SNG), and has now been published. The revised guideline reflects the increasing integration of classical CSF parameters, modern biomarkers, and translational approaches bridging research and clinical application. It strengthens the role of CSF diagnostics as a reference method, complemented by blood-based approaches within a tiered diagnostic concept.

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CSF examination is a central component of diagnostics in neurology, psychiatry, and neurosurgery. It is an important—and in some cases indispensable—method for diagnosing inflammatory diseases of the nervous system and meninges, detecting subarachnoid hemorrhage not visible on imaging, and identifying malignant spread into the CSF space and meninges. Measurement of CSF opening pressure in idiopathic intracranial hypertension and the CSF tap test in normal pressure hydrocephalus are also diagnostically confirmatory procedures with therapeutic implications.

A key update is that, according to the revised McDonald criteria 2024, a diagnosis of multiple sclerosis can now be established based on CSF findings. This applies to patients with typical MS symptoms or a radiologically isolated syndrome who fulfill MRI criteria for dissemination in space and show isolated oligoclonal bands in CSF and/or intrathecally synthesized kappa free light chains (kFLC).

The guideline also includes new recommendations for performing lumbar puncture (LP) in patients receiving anticoagulation (vitamin K antagonists, direct oral anticoagulants [DOACs], and dual antiplatelet therapy). In such cases, the indication for LP is often an individual decision requiring interdisciplinary discussion. The risk of interrupting anticoagulation must be weighed against the increased bleeding risk during and after LP.

A practice-relevant clarification concerns informed consent prior to LP: written consent remains mandatory, but a fixed waiting period (e.g., 24 hours or “overnight”) is not required. The decision can be made immediately after adequate information has been provided, provided the patient has decision-making capacity.

CSF diagnostics is also playing an increasingly important role in the diagnosis and differential diagnosis of neurodegenerative diseases. In addition to the routinely recommended basic CSF program (cell count, differential cytology, CSF lactate, Reiber diagram [albumin quotient, IgG, IgA, IgM], oligoclonal bands) to exclude inflammatory CNS processes, CNS-specific parameters serve as positive diagnostic markers, particularly in Alzheimer’s disease and amyotrophic lateral sclerosis. In Alzheimer’s disease, CSF biomarkers such as Aβ42, Aβ40 (or the Aβ42/40 ratio), total tau, and phosphorylated tau enable high diagnostic accuracy and support standardized interpretation algorithms. Newly included and significantly upgraded is the role of blood-based biomarkers, particularly pTau isoforms (pTau217) and Aβ42/40 in plasma. These can complement CSF diagnostics in a targeted manner but cannot yet fully replace it.

An important advancement concerns biomarkers in motor neuron diseases. Neurofilaments (particularly NfL and NfH) are validated cross-disease markers of axonal damage. In amyotrophic lateral sclerosis, they support diagnosis, are prognostically relevant (disease progression), and are increasingly used as surrogate markers in clinical studies.

 

[1] Tumani H., Petereit H.-F. et al., Lumbalpunktion und Liquordiagnostik, S1-Leitlinie, 2026, in:

Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Therapie in der Neurologie.

Online: www.dgn.org/leitlinien  (abgerufen am 17.03.2026)