09/02/2026 - General information
Researchers from the Barcelonaβeta Brain Research Center (BBRC), a research center of the Pasqual Maragall Foundation, together with Hospital del Mar and its research institute (HMRIB), have published in Nature Scientific Reports the results of a standardized protocol to reduce and control headache, the most common complication after a lumbar puncture. Lumbar puncture is a key procedure in neurology, as it allows the collection of cerebrospinal fluid (CSF), a particularly valuable sample in the context of neurodegenerative diseases for the analysis of biomarkers relevant to brain health and, especially, to research and clinical practice.
In Alzheimer's research, CSF biomarkers are essential to better understand the disease at very early stages, even before symptoms appear, and to drive prevention strategies and the development of treatments. In this context, the research team evaluated a protocol that 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 to advance the study of Alzheimer's biomarkers in cerebrospinal fluid, and minimizing discomfort associated with the procedure is key. Standardizing every step, from hydration to needle type and post-procedure rest, allows us to reduce headache and make the procedure more tolerable, especially when larger volume extractions are required," explains Dr. Oriol Grau, leader of the Clinical Research and Risk Factors for Neurodegenerative Diseases Group at the BBRC and the Hospital del Mar Research Institute (HMRIB), and co-author of the study.
The key contribution of ALFA cohort volunteers
The study was conducted with cognitively healthy individuals from the ALFA cohort, promoted by the "la Caixa" Foundation, and was made possible thanks to the participation and commitment of volunteers who make preventive Alzheimer's research feasible.
The study analyzed 1,147 lumbar punctures performed in 724 ALFA study participants, following a standardized protocol that combines controlled hydration (500 ml of 0.9% saline solution intravenously), use of a 22G atraumatic "pencil-point" needle, extraction of 13.5-15 ml of CSF without negative pressure, and 45 minutes of supervised rest after the procedure.
The results show that, with this protocol, post-procedure headache occurred in 9.6% of participants at 24 hours and 4.7% at 7 days. In participants who did experience headache, it was almost always mild (95.5% of cases at 24 hours; 87% at 7 days), and no severe cases or complications requiring an epidural blood patch or hospitalization were reported.
"The application of a standardized protocol has made it possible to reduce severe complications after cerebrospinal fluid extraction by lumbar puncture to zero," adds Dr. Antonio Montes, Head of the Pain Unit at Hospital del Mar, researcher at its research institute, and corresponding author of the study.
As this is an observational study without a control group, the researchers contextualize the improvement achieved by comparing their results with existing literature. Specifically, three similar studies reported post-lumbar puncture headache rates at 24 hours of 24.8%, 11.9%, and 9%. In addition, those studies reported more severe events such as hospitalization (2.5%) or the need for a blood patch (1.4%), whereas no such complications were observed in the present study.
Exploratory analysis also showed that at 24 hours, headache was more frequent in individuals with a history of chronic pain, with low or very high body mass index, and when the puncture was performed at lower lumbar levels.
"Beyond safety, we care deeply about ensuring the best possible experience for our participants. A clear and reproducible protocol facilitates clinical practice, improves follow-up, and helps ensure that if headache occurs, it can be managed easily with standard measures and without complications," explains Anna Soteras, Director of the Clinical Operations Platform at the BBRC and co-author of the study.
The study stands out for its large sample size, the systematic application of a homogeneous protocol, and structured follow-up at 24 hours and 7 days. However, the authors note that the absence of a control group and the highly specific context in which the study was conducted, with a relatively narrow age range, may limit the generalizability of the results to other settings and populations.
Improving the tolerability of lumbar puncture is not a minor issue: it is a key condition for continuing to advance preventive research. More standardized protocols with fewer complications help reduce fear and encourage more people to undergo the procedure with confidence. This is especially relevant because cerebrospinal fluid provides essential information on Alzheimer's biomarkers and allows scientific questions to be addressed earlier and more effectively, ultimately leading to 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.
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