Clinical short communication
Low cerebrospinal fluid volume and the risk for post-lumbar puncture headaches

https://doi.org/10.1016/j.jns.2020.117059Get rights and content

Highlights

  • Headache is a common adverse event post lumbar puncture (LP) procedures.

  • We examined if low cerebrospinal fluid (CSF) is linked to post LP headaches risk.

  • Both, low CSF volumes and age were associated with post-LP headache occurrence.

  • CSF volumes can be assessed based on subjects' pre-existing MRI scans.

  • These should be taken into consideration prior to LP interventions.

Abstract

Background:

Cerebrospinal fluid (CSF) is essential for the medical workup of patients with neurological conditions and for disease-modifying clinical trials. Post- lumbar puncture (LP) headache is influenced by both operator and patient-related factors, including needle type and gauge, age, and gender.

Objectives: We aimed to assess whether CSF volume measured based on pre-procedural brain MRI is associated with the risk of developing a post-LP headache.

Methods: In total, n = 117 participants (n = 58 Parkinson's disease patients, and n = 59 healthy controls) underwent an LP and CSF collection. Of those, n = 89 underwent MRI scans prior to the LP procedure acquiring high-resolution 3D magnetization-prepared rapid gradient echo (MP-RAGE) T1-weighted images using a 3 T MR scanner. Clinical and behavioral assessments were performed for all participants, and CSF was assessed for content. The T1-weighted images were segmented producing gray matter, white matter, and CSF probability maps.

Results: Thirteen participants (11.1%) experienced post-LP headache. They were younger (p = .033) and had lower CSF volumes (p = .040) compared to participants that did not develop a post LP headache.

Conclusions: The results of this pilot study suggest that low CSF volumes might increase the risk for the occurrence of post-LP adverse events and should be taken into consideration when planning LP's.

Introduction

Cerebrospinal fluid (CSF) is essential for the medical workup of patients with neurological conditions. Lately, it is also becoming a key player in the search for novel biomarkers for neurodegenerative diseases [1]. One of the common complications of lumbar punctures (LP) for the collection of CSF is a persistent orthostatic headache, affecting up to 35% of those undergoing the procedure [2]. Many factors have been suggested to influence the incidence of post-LP headaches including, type of used needle (traumatic vs. a-traumatic), needle gauge, Body Mass Index (BMI), age, gender, operator experience, multiple dural punctures, and patients' position [3].

To date, the pathophysiological basis of post-LP headaches remain unclear [4,5]. Yet, two possible underlying pathological mechanisms were proposed. One hypothesis suggested that CSF loss through the dural rent leads to the stimulation of sensory cranial nerves causing headaches. Alternatively, following LP and CSF collection, intracranial hypotension and cerebral vasodilation can lead to vascular-type headache as a result of volume compensation mechanism taking place, where CSF volume loss is balanced by a change in blood volume within the first 24 hours post LP [4].

In a recent multi-center study in a large sample of 683 participants that included Parkinson's disease (PD) and healthy controls (HCs); gender, younger age, and height were found to be significant contributing factors for the occurrence of post-LP headache in the HCs group, but not in PD [1], indicating that low total CSF volume might play a key role in the risk for adverse event development post-LP.

Based on this, we aimed to examine the relationship between whole-brain CSF volumes assessed based on MRI and the occurrence rate of post-LP headache incidents in PD compared to HCs. We hypothesized that due to lower brain atrophy rates, lower CSF volumes in the HC group would be associated with higher rates of post-LP headache in this group compared to PD patients.

Section snippets

Study participants

This is a sub-study of two concurrent observational studies at the Tel Aviv Sourasky Medical Center (TASMC) between the years 2015–2019; BeaT-PD and the Parkinson's progression marker initiative (PPMI), aimed to identify biomarkers for risk and progression of PD. Both studies enrolled patients with PD and healthy controls (HC). This study was approved by institutional review board (IRB). All enrolled participants gave their informed, signed consent upon entering the study.

PD Patients were

Demographic and clinical characteristics of the study participants

A total of n = 58 patients with PD, and n = 59 HC underwent LP. Table 1 summarizes the demographic and clinical characteristics of the study participants. PD patients were found to be significantly older than HCs (62.16 ± 9.46 vs. 58.78 ± 9.33 respectively; p < .001), however, they were not found to experience different rates of post LP headaches (8.47% vs. 13.55%; p = .291).

One PD participant was found to harbor an indolent lymphoma based on his LP (WBC = 28, RBC = 2, protein = 54 mg/dl, and

Discussion

Identifying factors that predict the likelihood of post-LP headaches is of high importance for both clinical and research settings. In this study, 11.1% of the enrolled participants experienced a post-LP headache, all being self-limited and not requiring a blood patch. Based on the obtained results, LP+ participants were significantly younger and had lower CSF volumes compared to LP-, suggesting that total brain CSF% which can be automatically assessed in advance based on pre-existing

Conclusions

While our findings are novel and require further confirmation, lower CSF volumes seem to increase the risk for post-LP headache occurrence. A comprehensive score of CSF volumes is needed in order to reliably establish a predicative model for post-LP headache. This can be achieved in future studies utilizing MRI prior to the procedure.

Acknowledgments

This study was funded by Biogen Inc., and the Michael J Fox Foundation grant #16137.

Authors' contribution.

AD: Imaging data analysis, statistical analysis, writing of the manuscript.

NO: Data collection, writing of the manuscript.

TG: Manuscript revision.

MK: Data collection, manuscript revision.

YM: Data collection, manuscript revision.

JC: Manuscript revision.

OA: Manuscript revision.

NG: Conception, manuscript revision.

AM: Conception, manuscript revision.

AT: Conception, data collection, statistical

Author disclosures

AD, NO, YM & OA: have nothing to disclose. TG: reports advisory board membership with honoraria to her and to her Institution Abbvie Israel, Neuroderm Ltd. and Allergan, research support from Phonetica Ltd., Israeli Innovation Authority, Sagol School of Neuroscience (Brain Boost) and Parkinson's Foundation. She received travel support for herself and her team from Abbvie, Allergan, Medisson, and Medtronic. MK: Received payment for lectures from Abbvie and Teva. JC: Is a former employee and

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