A standardised protocol reduces post-lumbar puncture headache after cerebrospinal fluid extractions

Investigators at the Barcelonaβeta Brain Research Center (BBRC), research center of the Pasqual Maragall Foundation, together with Hospital del Mar Research and its research center (HMRIB), have published in Nature Scientific Reports the results of a standardised protocol to reduce and control headache, the most frequent complication after a lumbar puncture. 

Lumbar puncture is a key test in neurology, because it allows the collection of cerebrospinal fluid (CSF), a sample that is particularly valuable in the context of neurodegenerative diseases for analysing biomarkers relevant to brain health and, in particular, for research and clinical practice.

In Alzheimer's research, CSF biomarkers are essential for better understanding the disease at very early stages, even before symptoms appear, and for advancing prevention strategies and the development of treatments. In this context, the research team has evaluated a protocol which reduces one of the most common side effects of lumbar puncture: headache, a type of pain that may appear transiently after the procedure.

“Lumbar puncture is an essential test for advancing the study of Alzheimer's biomarkers in CSF, and minimising the discomfort of this test is key. Standardising each step, from hydration up to the type of needle and rest, allows us to reduce headaches and make this procedure more bearable, especially when large-volume extractions are needed,” explains Dr. Oriol Grau, Leader of BBRC's Clinical Research and Risk Factors for Neurodegenerative Diseases Group and co-author of the study.

 The key contribution of the ALFA cohort volunteers

The work was conducted with cognitively healthy people from the ALFA cohort, promoted by ”la Caixa” Foundation, and was made possible thanks to the participation and commitment of individuals who, voluntarily, make preventive research into Alzheimer's disease viable.

The study analysed 1147 lumbar punctures performed on 724 participants in the ALFA study, following a standardised protocol combining: controlled hydration (500 ml of 0.9% saline solution intravenously), use of a non-traumatic, 22G pencil point needle; CSF collection (13.5–15 ml) without negative pressure; and 45 minutes of supervised rest after the procedure.

As shown in the results, with this protocol, the incidence of headache after this test was 9.6% at 24 hours and 4.7% at 7 days. For those people who did experience headache, it was almost always a mild pain (95.5% of cases at 24 hours, 87% at 7 days), and there were no reports of severe cases or complications requiring a blood patch (a procedure in which the patient's own blood is injected to seal a possible cerebrospinal fluid leak), or hospitalisation.

“The application of a standardized protocol has made it possible to reduce serious complications to 0 after cerebrospinal fluid extraction after lumbar puncture,” adds Dr. Antonio Montes, head of the Pain Unit at Hospital del Mar and researcher at its research institute and corresponding author of the study.

Because this is an observational study that does not include a control group, investigators contextualise the improvement of this protocol by comparing its results with existing literature. Specifically, when reviewing three similar studies, the reported post-dural headache rates were 24.8%, 11.9%, and 9% at 24 hours; additionally, more severe events were reported in those studies, such as hospitalisation (2.5%) or the need for a blood patch (1.4%), while no complications of this type were observed in this study.

The exploratory analysis also found that, at 24 hours, headaches were more frequent in individuals with a history of chronic pain, a low or very high body mass index, and when the puncture was conducted at lower lumbar levels.

“In addition to safety, we care deeply about ensuring that our participants have the best possible experience. A clear, reproducible protocol makes clinical practice easier, improves follow-up, and helps ensure that, if headaches do occur, they can be easily managed with standard measures and without complications,” explains Anna Soteras, Director of BBRC’s Clinical Operations Facility and co-author of the study.

The study stands out for its large sample size, the systematic application of a homogeneous protocol, and a structured follow-up at 24 hours and at 7 days. However, the authors point out that the absence of a control group and the fact that the study was conducted in such a specific context, with a relatively limited age range, may limit the generalisation of the results in other settings and populations.

Improving the tolerability of lumbar punctures is no trivial matter: it is a key condition for being able to continue advancing preventative research. Having more standardised protocols with fewer complications helps reduce fear and makes it easier for more people to agree to undergo this test more confidently. This is particularly relevant, because cerebrospinal fluid provides essential information about Alzheimer's biomarkers, and it allows for earlier and better answers to scientific enquiries which, with the passage of time, may translate into more accurate diagnoses and more effective prevention strategies.

Reference article

 Pérez-García G. et al. Protocol to avoid post-dural puncture headache after large-volume cerebral spinal fluid extraction in a prospective observational memory clinic study. Scientific Reports (2026) 16:1931.  DOI: 10.1038/s41598-025-31634-6.