# Quality of life in patients with spontaneous intracranial hypotension: A systematic review and meta-analysis

J Ognard, G El Hajj, S Ghozy, J K Cutsforth-Gregory, A A Madhavan, R

Kadirvel, D F Kallmes, W Brinjikji

► To cite this version:

J Ognard, G El Hajj, S Ghozy, J K Cutsforth-Gregory, A A Madhavan, et al.. Quality of life in patients with spontaneous intracranial hypotension: A systematic review and meta-analysis. Revue Neurologique, 2025, 181 (8), pp.725 - 741. 10.1016/j.neurol.2025.08.002. hal-05288161

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https://hal.univ-brest.fr/hal-05288161v1

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General review

# Quality of life in patients with spontaneous intracranial hypotension: A systematic review and meta-analysis

<figure><img src="image_2.png" /></figure>

J. Ognard<sup>a,b,*</sup>, G. El Hajj<sup>a</sup>, S. Ghozy<sup>a,c</sup>, J.K. Cutsforth-Gregory<sup>d</sup>, A.A. Madhavan<sup>a</sup>, R. Kadirvel<sup>c</sup>, D.F. Kallmes<sup>a</sup>, W. Brinjikji<sup>a</sup>

## INFO ARTICLE

Article history:

Received 11 April 2025

Received in revised form

30 July 2025

Accepted 4 August 2025

Available online 13 August 2025

Keywords:

Quality of life

Symptomatic intracranial

hypotension

Meta-analysis

CSF-venous fistula

CSF leak

## ABSTRACT

**Background.** – Not only are diagnosis and management of spontaneous intracranial hypotension (SIH) challenging due to heterogeneous symptoms and limited treatment effectiveness, but SIH's impact on health-related quality of life (HRQoL) is under-documented.

**Objectives.** – In this systematic review, we aim to evaluate the assessment of QoL in SIH patients, identify impacted QoL domains, and explore treatment-related changes in QoL with a meta-analysis.

**Methods.** – Following PRISMA recommendations, we conducted a systematic literature search using a comprehensive set of keywords related to QoL and SIH. Databases were searched from the inception to July 2025. Studies were included if they provided reports on the quality of life for SIH patients. A meta-analysis using mean difference (MD) of baseline and after-treatment QoL scores was conducted. The risk of bias was assessed using the Newcastle-Ottawa scale.

**Results.** – Of 1435 initial publications, 20 studies met the inclusion criteria, representing a total of 1106 patients with SIH. EQ-5D-5L and HIT-6 were the most frequently used tools, with pooled results showing significant improvement post-treatment in perceived health (Visual analog scale score improved from 38.9 to 72.2; MD of 42.4 [95% CI 26.2–58.7]) and headache impact (HIT-6 scores improved from 66.1 to 49.3; MD of 20.1 [95% CI: 14.7–25.6]). Despite treatment, studies reported moderate to severe physical, mental, and social limitations.

**Discussion.** – The reporting of QoL is inconsistent and the tools used to assess QoL in SIH patients are heterogeneous. While treatment provides help, some symptoms persist and highlight the need for specific QoL assessment, with tools tailored to SIH.

© 2025 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

<footnote><sup>a</sup>Department of Radiology, Mayo Clinic, Rochester, MN, USA</footnote>

<footnote><sup>b</sup>Brest University, LATIM, Inserm UMR1101, CHU de Brest, Brest, France</footnote>

<footnote><sup>c</sup>Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA</footnote>

<footnote><sup>d</sup>Department of Neurology, Mayo Clinic, Rochester, MN, USA</footnote>

<footnote>* Corresponding author at: CHU de Brest, Hôpital de la Cavale-Blanche, boulevard Tanguy-Prigent, 29609 Brest cedex, France.
E-mail address: julien.ognard@chu-brest.fr (J. Ognard).
https://doi.org/10.1016/j.neurol.2025.08.002</footnote>

<footnote>0035-3787/© 2025 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</footnote>
What is already known on this topic?

* Quality of life (QoL) in spontaneous intracranial hypotension (SIH) is poorly characterized: prior studies have primarily focused on “symptom resolution” or headache intensity, with few using validated QoL instruments.

What this study adds?

* The Headache Impact Test-6 (HIT-6) and the EuroQol 5-Dimension (EQ-5D-5L) scales are both frequently used and sensitive to measuring QoL changes over time in SIH.

* SIH severely impairs physical, mental, social, and occupational functioning, with particularly profound effects on headache-related disability, mental health, and ability to work. While pooled analyses show significant QoL improvements after treatment, many patients continue to experience residual symptoms.

How this study might affect research, practice, or policy?

* Clinicians and researchers should incorporate validated, multi-domain QoL instruments into standard SIH assessment to capture the full patient experience and guide individualized treatment strategies.

# 1. Abbreviations

<table><tr><td>5D</td><td>15-Dimension Health-Related Quality of Life Instrument</td></tr><tr><td>C-SSRS</td><td>Columbia-Suicide Severity Rating Scale</td></tr><tr><td>CSF</td><td>cerebrospinal fluid</td></tr><tr><td>DASS-21</td><td>Depression Anxiety Stress Scale-21</td></tr><tr><td>DHI</td><td>Dizziness Handicap Inventory</td></tr><tr><td>EBP</td><td>epidural blood patching</td></tr><tr><td>EQ-5D-5L</td><td>EuroQol 5-Dimensions 5-Levels</td></tr><tr><td>GAD-7</td><td>Generalized Anxiety Disorder 7-item scale</td></tr><tr><td>HADS</td><td>Hospital Anxiety and Depression Scale</td></tr><tr><td>HDI</td><td>Headache Disability Index</td></tr><tr><td>HIT-6</td><td>Headache Impact Test-6</td></tr><tr><td>HRQoL</td><td>Health-Related Quality of Life</td></tr><tr><td>IQR</td><td>interquartile range</td></tr><tr><td>MHD</td><td>monthly headache days</td></tr><tr><td>MIDAS</td><td>Migraine Disability Assessment</td></tr><tr><td>MSQ</td><td>Migraine-Specific Quality of Life</td></tr><tr><td>NDI</td><td>Neck Disability Index</td></tr><tr><td>NEI-VFQ-25</td><td>National Eye Institute Visual Function Questionnaire</td></tr><tr><td>NOS</td><td>Newcastle-Ottawa Scale</td></tr><tr><td>PHQ-9</td><td>Patient Health Questionnaire-9</td></tr><tr><td>PRISMA</td><td>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</td></tr><tr><td>PROMIS</td><td>Patient-Reported Outcomes Measurement Information System</td></tr><tr><td>QoL</td><td>quality of life</td></tr></table>

<table><tr><td>RINVR</td><td>Rhodes Index of Nausea, Vomiting and Retching</td></tr><tr><td>ROS</td><td>risk of bias</td></tr><tr><td>SD</td><td>standard deviation</td></tr><tr><td>SE</td><td>standard error</td></tr><tr><td>SF-36</td><td>Short Form Health Survey 36</td></tr><tr><td>SIH</td><td>spontaneous intracranial hypotension</td></tr><tr><td>SMD</td><td>standardized mean difference</td></tr><tr><td>SSS</td><td>Symptom Severity Scale</td></tr><tr><td>THI</td><td>Tinnitus Handicap Inventory</td></tr><tr><td>VAS</td><td>Visual Analog Scale</td></tr><tr><td>WPI</td><td>Widespread Pain Index</td></tr></table>

# 2. Introduction

Spontaneous intracranial hypotension (SIH) results from spontaneous cerebrospinal fluid (CSF) leaks from the spinal dura mater that cause low intracranial CSF volume and pressure [1]. Likely underestimated, SIH is still considered rare, with an estimated incidence of approximately 5 per 100,000 individuals annually. Diagnosing SIH poses significant challenges due to the lack of definitive tests but should however be considered in any patient presenting with orthostatic headache, cough headache, or new daily persistent headache [2]. The clinical expression of SIH is heterogeneous, and patients frequently report a constellation of symptoms that includes neck stiffness, nausea, tinnitus, hearing disturbances, visual impairments, cognitive difficulties, and vestibular dysfunction, such as dizziness and imbalance [3]. Recent improvement in myelography techniques to detect and localize spinal CSF leaks have improved diagnosis and furthered our understanding of the types of CSF leaks at play [4]. These mainly include ventral dural tears, lateral dural tears, and CSF-venous fistulas. Therapeutic strategies for SIH are diverse and challenging. Conservative options such as bed rest, hydration, and caffeine generally provide temporary, if any, relief. Epidural blood patching (EBP), the primary intervention, shows success rates of 36 to 64% [5], with larger volumes and targeted approaches enhancing effectiveness, but recurrences are frequent. Surgical options such as dural repair and endovascular embolization of CSF-venous fistulas show promise in selected cases [6,7]. Long-term recovery in SIH is complicated by rebound intracranial hypertension, multiple interventions, limited treatment effectiveness, chronic and fluctuating symptoms, and delayed care. The impact of SIH may then surpass physical symptoms. SIH affects psychological and social well-being and disrupts daily and work life [8]. Health-related quality of life (HRQoL) refers to the perceived physical and mental health status and social functioning, which reflects the overall impact of medical or therapeutic interventions [9]. Chronic diseases are assumed to lower the HRQoL of middle-aged and older adults [10]. Despite the substantial burden on SIH patient QoL, these effects remain insufficiently documented. Treatment effectiveness is often simplified to “symptom resolution” [11] or pain assessments overlooking detailed QoL. A systematic review by Amrhein et al. [5] of 139 studies found that 84.9% relied on non-validated symptom resolution measures, and 12.2% used a numeric pain rating scale. Furthermore, the paucity of
comprehensive analyses synthesizing these data enhances
the need for a systematic review to explore and consolidate
current knowledge on the QoL of patients with SIH. In this
systematic review, we aim to synthesize how QoL is assessed
in patients with SIH, identify the QoL domains most affected,
and quantify post-treatment changes via meta-analysis, with
a subgroup analysis by treatment type.

# 3. Methods

## 3.1. Standard protocol approvals

No ethical approval was required as the current study
involved analyzing and synthesizing previously published
data and information from secondary use of deidentified
electronic databases (Code of Federal Regulations, 45 CFR
46.102). No protocol was registered. The study was not funded.
All data to conduct or reproduce the study are available online.
It was conducted and reported per the preferred reporting
items for systematic reviews and meta-analyses (PRISMA)
2020 recommendations [12].

3.2. *Search strategy*

The literature search, duplicate removal, and article screening
and evaluation processes were conducted using the Nested
Knowledge® (NK) AutoLit® software, version 1.89 (NK, St
Paul, Minnesota, USA).

A systematic review of the English-language literature was
performed using the following databases: PubMed/Medline,
Google Scholar, Web of Science, and Scopus. The search
included a combination of keywords for QoL (“questionnaire,”
“quality of life,” “health-related quality of life,” “work
ability”) AND for the SIH (“spontaneous intracranial hypo-
tension,” “cerebrospinal fluid leak,” “low cerebrospinal fluid
volume headaches”, “low cerebrospinal fluid pressure heada-
che,” “intracranial hypotension,” “spinal cerebrospinal fluid
leak, “cerebrospinal fluid-venous fistula”) as well as all their
acronyms. MeSH terms included “intracranial hypotension”
(D019585), “cerebrospinal fluid leak” (D065634), and “quality
of life” (D011788). In addition to the database search, we
searched through unpublished results of ongoing/just termi-
nated clinical trials. We also reviewed the bibliographies of
included studies and consulted field experts to identify missed
articles (Supplemental material – Appendix 1).

3.3. Eligibility criteria and study selection

The study selection process was also conducted using NK
AutoLit® software. Initially, titles and abstracts were scree-
ned independently by two authors (JO, GEH) to identify
potentially eligible studies. Subsequently, the full-text articles
of the selected studies were thoroughly assessed against the
predetermined criteria. Any discrepancies in study selection
were resolved through consensus or consultation with the
senior author (WB). We included all studies providing reports
on the quality of life of patients presenting with spontaneous
intracranial hypotension. All publications from the inception
to July 24, 2025, were screened. Exclusion criteria consisted of

no statement regarding the QoL related to SIH, pediatric
population, secondary intracranial hypotension (e.g., post-
dural puncture headaches), animal studies, imaging study,
conference abstract, case reports, or review article.

3.4. Data extraction and study outcomes

A predefined data extraction form was employed. Extracted
data were considered both for treated and non-treated
patients, and encompassed study characteristics (author,
publication year, study design) and patient characteristics
(number of patients, number of females, age, symptom
duration, follow-up duration, characteristics of the treatment,
outcome, QoL measures, and SIH-score [13]). Any unstandar-
dized QoL assessment was also recorded. Any discrepancies or
conflicts were resolved through discussion and consensus
with the assistance of the senior author (WB).

The risk of bias (ROB) was assessed using the Newcastle-
Ottawa scale (NOS) [14] for assessing the quality of non-
randomized studies in meta-analyses (Supplemental
material – Appendix 2).

3.5. Statistics

The estimation of means and standard deviations (SDs) from
medians and interquartile ranges (IQRs) was conducted using
the method proposed by Wan et al. and reported in
*Supplemental material – Appendices 3 and 4* [15]. Only when
available, the intervention effect on QoL was reported and
pooled across studies. An absolute standardized coeffi-
cient = |('after treatment score' - 'baseline score') / 'SD of the
baseline score'| was used to report the treatment effect among
QoL tools across studies (*Supplemental material – Appendix 5*).
To explore the effect on various outcome measurement
methods with comparable parameters and minimize the
effects of baseline differences in studies with small sample
sizes, we calculated mean differences (MD). The direction of the
effect was consistently defined as ameliorative, with higher MD
indicating greater improvement. Standard errors (SEs) and 95%
CI (confidence interval) are provided to indicate the precision of
the effect size estimate. If at least three studies reported a QoL
score before and after treatment, a meta-analysis was
performed (*Supplemental material – Appendix 4*). Analyses
were planned to quantify changes in QoL after treatment via
meta-analysis. A random-effects meta-analysis was performed
to account for within-study variability and between-study
heterogeneity, with the between-study variance estimated
using the restricted maximum likelihood (REML) method, for
Headache Impact Test-6 (HIT-6) and EuroQol 5-Dimension 5-
Level (EQ-5D-5L) visual analog scale (VAS) [16]. Both tools were
chosen because the included studies provided enough data to
perform the meta-analysis. Heterogeneity among studies was
assessed using Cochran's Q test and the I-squared statistic.
Forest plots were generated to represent individual study
effects and the pooled estimate, and funnel plots were created
to assess potential publication bias (*Supplemental material –
Appendices 6 and 7*). Egger's regression test was performed to
assess funnel plot asymmetry for HIT-6 as the number of
studies exceeded the recommended threshold of 10. To
evaluate the robustness of the results, we conducted a leave-
one-out sensitivity analysis by systematically omitting one study at a time to identify any influential studies affecting the overall effect size (Supplemental material – Appendices 8 and 9), and subgroups analyses were also used to investigate heterogeneity, according to the treatment group for HIT-6 (Supplemental material – Appendix 10). Effect models were computed only when at least three studies were available per group. Subgroup analyses were not conducted for the EQ-5D-5L due to an insufficient number of studies (fewer than three per subgroup). Analyses were conducted using R (version 4.5.1) with the ‘meta’ package (version 8.2-0).

# 4. Results

## 4.1. Study selection and inclusion

Of the initial 1435 publications identified, 269 were duplicates and 20 of 33 eligible articles met the inclusion criteria and provided sufficient information to be included in the systematic review [8,17–35]. Specifically, 15 studies addressed HIT-6, 12 focused on both physical and mental quality of life (QoL), and 9 were dedicated to QoL assessment. The descriptive characteristics of each included study are presented in Table 1, while excluded studies are detailed in Fig. 1. PRISMA checklist can be found in Supplemental material – Appendices 12 and 13.

## 4.2. Characteristics of included studies

The 20 included studies were published between 2020 and 2025 and included a total of 915 patients with SIH. Six studies were conducted in the United States, eleven in Europe (four in Germany, three in France, two in Switzerland, one in the United Kingdom, one in Austria), two in Asia (Korea and China) and one in Australia. Study durations ranged from 2 to 12 months, but patients were studied from 2005 to 2024, with median baseline participant ages ranging from 44 to 63 years. The studies were primarily conducted among patients with confirmed SIH and mostly included women. Three studies were cross-sectional surveys.

## 4.3. Heterogeneity of definitions and settings

There was heterogeneity of type of treatment assessed in the studies, as well as the time harvesting the QoL items regarding the treatment, or the start of the disease. Two studies investigated CT-guided occlusion with before-after measurements [18,29], while three others assessed all types of treatments including one with a before-after approach [8] and others with ongoing support [17,22]. The effects of EBP were explored in four studies [19,34,35], including one focusing on long-term outcomes according to international classification of headache disorders, 3rd edition (ICHD-3) positive or negative patients [23]. One study declared more than 90% of patients treated with EBP and focused on their QoL, but also included suspected diagnosis of SIH patients [27]. One study combined results for embolization and surgery [21] and five surgery [25,26,28,30,32], while four others focused exclusively on embolization [20,24,31,33], which are therefore studies of the subgroup of patients with CSF-venous fistulas.

The most heterogeneous level was the difference between tools used to assess QoL in studies. Supplemental material – Appendix 10 reports the link between the subitems that were used to assess the QoL, and the corresponding field of QoL, and Table 2 reports the QoL subitems and corresponding instruments to evaluate function and QoL together with the number of contributing studies.

The meta-analysis of reported HIT-6 scores showed considerable heterogeneity across all included studies, with an overall I² of 98.2%. To investigate sources of heterogeneity, a subgroup analysis (Supplemental material – Appendix 10) was performed based on intervention type, grouping studies into four categories: percutaneous seal, epidural blood patch, embolization, and surgery. The test for subgroup differences was statistically significant (Q = 11.2, P = 0.01), confirmed that intervention type contributed significantly to the observed heterogeneity in the overall meta-analysis. A leave-one-out sensitivity analysis was conducted to assess whether any single study disproportionately influenced the overall heterogeneity. For HIT-6, (Supplemental material – Appendix 9) omitting Caroll et al. [23] increases the pooled MD to 23.4 and reduces the I² to 90.5%. For EQ-5D-5L, the meta-analysis showed also considerable heterogeneity with an overall I-squared of 95.3% and results showed minimal change in the pooled effect size and heterogeneity measures when individual studies were omitted (Supplemental material – Appendix 8).

Considering the ROB, most studies achieved low risk in the selection domain, showing adequate case definition, representative samples. The heterogeneity of design, particularly in the absence of controls, lead to higher risks in the comparability domain stars, also due to differences in the outcome reporting.

## 4.4. General health perception

Table 2 summarizes the results of the subitems and scale assessing QoL across all studies. The VAS component of the EQ-5D-5L was the most used tool to summarize HRQoL, found in six [17,21,24–26,33] of nine [8,18,27] studies reporting general health perception. Baseline HRQoL was significantly altered and after treatment evaluation showed marked improvement, with pooled mean scores rising from 38.9/100 (95% CI: 35.6–42.2) at baseline (n = 246, five studies) to 72.2/100 (95% CI: 69.3–75.1) after treatment (n = 298, six studies).

This large score change translates into a large effect size in the meta-analysis (five studies, Fig. 2), indicating significant improvement in patients' perceived health status after treatment, with MD of 24.30 (95% CI: 13.3–35.2) (with patient treated by embolization and surgery) [21], 30.0 (95% CI: 25.1–34.9) (surgery) [25], 33.0 (95% CI: 28.6–37.4) (surgery) [26], 60 (95% CI: 50.5–69.6) (embolization) [24] and 65.2 (95% CI: 57.2–73.3) (embolization) [33] yielding an overall MD (random-effects model, I² 95.3%) of 42.3 (95% CI: 26.2–58.7).

## 4.5. Our pooled results from the two studies by Jesse et al. show that the 15 dimensions (15D)

HRQoL index increased from 0.8 (95% CI: 0.78–0.82) at baseline (n = 100) to 0.89 (95% CI: 0.87–0.91) after treatment (n = 79)
<table><caption>Table 1 – Main characteristics of included studies and participants.</caption><thead><tr><th>Authors</th><th>Year</th><th>Journal</th><th>n</th><th>Study design</th><th>Country</th><th>Time span</th><th>Sex - Females n (%)</th><th>Age - Years Mean (SD) median [IQR]</th><th>Orthostatic HH n (%)</th><th>Duration of spt - M a</th></tr></thead><tbody><tr><td>Brinjikji et al. [20]</td><td>2022</td><td>J NeuroIntervent Surg</td><td>40</td><td>Retrospective</td><td>USA</td><td>NR</td><td>29 (72.5%)</td><td>57.4 (10.3)</td><td>38 (95%)</td><td>NR</td></tr><tr><td>Cagnazzo et al. [24]</td><td>2024</td><td>Interv Neuroradiol</td><td>21</td><td>Retrospective</td><td>France</td><td>2022-2024</td><td>15 (71.5%)</td><td>63 [58-71]</td><td>14 (66.7%)</td><td>33 (46)</td></tr><tr><td>Carroll et al. [23]</td><td>2024</td><td>Neurology</td><td>85</td><td>Prospective, case-control</td><td>USA</td><td>2016-2018</td><td>66 (77.7%)</td><td>42.5 (13.7)</td><td>71 (83.5%)</td><td>104.4 (97.2)</td></tr><tr><td>Cheema et al. [17]</td><td>2022</td><td>BMJ Open</td><td>64</td><td>Cross-sectional, survey</td><td>UK</td><td>2022</td><td>60 (94%)</td><td>42.8 (10.2)</td><td>NR</td><td>24 (0-240)</td></tr><tr><td>Davies et al. [19]</td><td>2020</td><td>World Neurosurg</td><td>86</td><td>Retrospective</td><td>Australia</td><td>2005-2020</td><td>53 (61.6%)</td><td>49.36 (range 13-85)</td><td>80 (93%)</td><td>NR</td></tr><tr><td>El Rahal et al. [32]</td><td>2025</td><td>Oper Neurosurg</td><td>40</td><td>Retrospective</td><td>Germany</td><td>2018-2022</td><td>29 (72.5%)</td><td>44 [35-58]</td><td>38 (95%)</td><td>NR</td></tr><tr><td>Goapper et al. [33]</td><td>2025</td><td>J Headache Pain</td><td>30</td><td>Prospective</td><td>France</td><td>NR</td><td>20 (66.7%)</td><td>60.4 (14.1)</td><td>19 (67%)</td><td>33 (44)</td></tr><tr><td>Ha et al. [34]</td><td>2025</td><td>J Headache Pain</td><td>53</td><td>Retrospective</td><td>Korea</td><td>2019-2024</td><td>33 (62%)</td><td>39.9 (11.1)</td><td>NR</td><td>NR</td></tr><tr><td>Jesse et al. [21]</td><td>2024</td><td>J Neurosurg Spine</td><td>21</td><td>Prospective, cohort</td><td>Switzerland</td><td>2022-2023</td><td>14 (66.7%)</td><td>51.7 (12.5)</td><td>16 (76.2%)</td><td>NR</td></tr><tr><td>Jesse et al. [8]</td><td>2022</td><td>J Neurol</td><td>79</td><td>Retrospective</td><td>Switzerland</td><td>2013-2020</td><td>53 (67.1%)</td><td>47.7 (12.6)</td><td>67 (84.8%)</td><td>NR</td></tr><tr><td>Kapan et al. [22]</td><td>2024</td><td>Wien Klin Wochenschr</td><td>86</td><td>Cross-sectional, survey</td><td>Austria</td><td>2023</td><td>73 (84.9%)</td><td>44 (12.01)</td><td>45(52.3%)</td><td>36<sup>b</sup> [24-48]</td></tr><tr><td>Kong et al. [35]</td><td>2025</td><td>Neurosurg Rev</td><td>68</td><td>Retrospective</td><td>China</td><td>2022-2024</td><td>41 (60.2%)</td><td>40.8 (9.3)</td><td>NR</td><td>1.1 (0.7)</td></tr><tr><td>Liao et al. [29]</td><td>2023</td><td>J Neurointervent Surg</td><td>11</td><td>Retrospective</td><td>France</td><td>2016-2022</td><td>5 (45%)</td><td>48.4 (14)</td><td>20 (100%)</td><td>NR</td></tr><tr><td>Liaw et al. [27]</td><td>2023</td><td>Neurology</td><td>95</td><td>Cross-sectional, survey</td><td>USA</td><td>2021-2022</td><td>66 (69.5%)</td><td>51.1 [15.5]</td><td>NR</td><td>7.7<sup>b</sup></td></tr><tr><td>Mamlouk et al. [18]</td><td>2022</td><td>Headache</td><td>35</td><td>Retrospective</td><td>USA</td><td>2018-2022</td><td>19 (54%)</td><td>60 (11)</td><td>35 (100%)</td><td>NR</td></tr><tr><td>Parizadeh et al. [31]</td><td>2023</td><td>J NeuroIntervent Surg</td><td>18</td><td>Retrospective</td><td>USA</td><td>2020-2022</td><td>13 (72%)</td><td>58.3 (12.4)</td><td>12 (67%)</td><td>36<sup>b</sup> (range 1-60)</td></tr><tr><td>Volz et al. [25]</td><td>2024</td><td>Neurol Clin Pract</td><td>74</td><td>Prospective</td><td>Germany</td><td>2020-2022</td><td>46 (62%)</td><td>45 [36-53]</td><td>NR</td><td>5<sup>b</sup> [2-14]</td></tr><tr><td>Volz et al. [26]</td><td>2024</td><td>J Neurol</td><td>100</td><td>Retrospective</td><td>Germany</td><td>2020-2023</td><td>61 (61%)</td><td>43.5 [36-53]</td><td>NR</td><td>5 (0.3-156)</td></tr><tr><td>Volz et al. [28]</td><td>2023</td><td>Cephalalgia</td><td>80</td><td>Retrospective</td><td>Germany</td><td>2020-2022</td><td>49 (61.2%)</td><td>44 (11.1)</td><td>78 (97.5%)</td><td>4 [2-13.5]</td></tr><tr><td>Wang et al. [30]</td><td>2020</td><td>Oper Neurosurg</td><td>20</td><td>Prospective, single-arm</td><td>USA</td><td>2012-2018</td><td>16 (80%)</td><td>51.3 (13.6)</td><td>18 (90%)</td><td>NR</td></tr></tbody></table>

HH: headaches; IQR: interquartile range; M: months; n: number; NR: not reported; SD: standard deviation; spt: symptoms.

<footnote>a To the treatment, or to the study.</footnote>

<footnote>b Mean median [IQR-] (SD) (range-).</footnote>
<figure><img src="image_3.png" /><figcaption>Fig. 1 - PRISMA 2020 flow diagram for new systematic reviews, which included searches of databases, registers and other sources. QoL: quality of life; SIH: spontaneous intracranial hypotension.</figcaption></figure>

[8,21]. Similarly, our pooled estimates from studies of Volz et al. [25,26] observed an improvement in the EQ-5D-5L index score from a median of 0.68 (IQR: 0.36-0.80) at baseline (n = 174) to 0.91 (IQR: 0.79-0.95) post-treatment (n = 174). However, Liaw et al. [27] found that the median Short Form Health Survey 36 (SF-36) general health component after treatment remained relatively low at 35.0 (IQR: 20.0-52.5) in 95 patients.

## 4.6. Physical health and functioning

Physical health was the most assessed field of QoL and only two studies [22,32] did not report any item or scale that could be linked. The EQ-5D-5L breakdown was only reported by Cheema et al. [17]: 54.8% of patients continued to report mobility limitations, 38.1% had difficulty performing self-care tasks, and 83.3% still experienced limitations in usual activities.

The HIT-6 was reported by 15 of 20 studies, pooled estimates showed initial scores averaging 66.1 (95% CI: 65.4-66.7) and decreasing to 49.3 (95% CI: 48.2-50.5) following treatment. Other headache related QoL tools, including migraine disability assessment (MIDAS) and migraine-specific QoL (MSQ), were each in only study [33]. In that study, 51.7% of patients reported a severe impact of headaches on QoL before treatment, compared to 3.4% after treatment.

Conversely, SF-36 median score for physical functioning was 45 (IQR: 30-70), while the score for physical role limitations was as low as 0 (highest impact) [3].

In Fig. 3, the meta-analysis of MD in HIT-6 scores are represented: Carroll et al. [23] showed the smallest effect with MD of 3.5 (95% CI: 1.7-5.2), but other studies exhibit moderate to large effects, with MD ranging from 9.3 (95% CI: 6.8-11.8) [28] to 29 (95% CI: 23.4-34.6) [24], and an overall effect of 20.1 (95% CI: 14.7-25.6). These were significantly different when pooling MD according to treatment (EBP, surgical, and/or embolization; Supplemental material – Appendix 11). Similarly, the HIT-6 scores (and EQ-5D-5L VAS) showed the largest absolute standardized coefficients (1.6 and 1.2, respectively; after VAS assessment of pain: 3.1), as one of the main (assessed and) responsive tools assessing QoL, reported in Fig. 4.

## 4.7. Mental health and emotional well-being

Eight studies [17,22,23,25,27,33-35] explored mental health using eight different scales: Columbia-suicide severity rating scale (C-SSRS), depression anxiety stress scale-21 (DASS-21), generalized anxiety disorder 7-item scale (GAD-7), hospital anxiety and depression scale (HADS), patient health questionnaire-9 (PHQ-9); or mental components: from SF-36, patient-reported outcomes measurement information system (PRO-MIS), and EQ-5D-5L. This category used the most subitems to assess QoL among studies (22 versus 11 for Physical Health, Supplemental material – Appendix 10). Liaw et al. [27] reported that 22.4% of patients assessed with C-SSRS had a lifetime history of suicidal behavior. Additionally, nearly half of the patients exhibited moderate to severe depressive symptoms
<table><caption>Table 2 – Summary of reported subitems and corresponding instruments to evaluate function and QoL of patients with SIH.</caption><thead><tr><th>Instrument</th><th>Abbreviation</th><th>Purpose</th><th>n of questions</th><th>Subitem</th><th>Range values</th><th>Value for favorable</th><th>Cutoff (moderate or higher impact)</th><th>n</th><th>Baseline QoL assessment, pooled<sup>a</sup></th><th>n</th><th>After treatment QoL assessment, pooled<sup>a</sup></th><th>n studies</th></tr></thead><tbody><tr><td>15D</td><td>15D</td><td>Health-related quality of life across 15 dimensions, single index score</td><td>15</td><td>-</td><td>0-1</td><td>Higher</td><td>0.79</td><td>100</td><td>0.80 (0.11)</td><td>79</td><td>0.89 (0.11)</td><td>2 [8,21]</td></tr><tr><td rowspan="2">Columbia-Suicide Severity Rating Scale</td><td rowspan="2">C-SSRS</td><td>Severity and intensity of suicidal ideation and behavior</td><td>Varies</td><td>Suicidal ideation</td><td>1-5</td><td>Lower</td><td>4</td><td>0</td><td>-</td><td>67</td><td>5 (7.5%)</td><td>1 [27]</td></tr><tr><td></td><td>Suicidal behavior</td><td>Presence</td><td>Absence</td><td>-</td><td>0</td><td>-</td><td></td><td>67</td><td>15 (22.4%)</td><td>1 [27]</td></tr><tr><td rowspan="3">Depression Anxiety Stress Scales - 21 items</td><td rowspan="3">DASS-21</td><td>Negative emotional states of depression, anxiety, and stress</td><td>21</td><td>Depression</td><td>0-21</td><td>Lower</td><td>7</td><td>74</td><td>10 [4-18]</td><td>74</td><td>6 [1-12]</td><td>1 [22]</td></tr><tr><td></td><td>Anxiety</td><td>0-21</td><td>Lower</td><td>7</td><td>74</td><td>6 [1-12]</td><td></td><td>86</td><td>54 (62.8%)</td><td>1 [25]</td></tr><tr><td></td><td>Stress</td><td>0-21</td><td>Lower</td><td>10</td><td>74</td><td>14 [7-20]</td><td></td><td>86</td><td>65 (75.6%)</td><td>1 [22]</td></tr><tr><td rowspan="2">Dizziness Handicap Inventory</td><td rowspan="2">DHI</td><td>Self-perceived handicapping effects of dizziness</td><td>25</td><td>-</td><td>0-100</td><td>Lower</td><td>31</td><td>96</td><td>41.1 (27.7)</td><td>96</td><td>32.8 (27.4)</td><td>2 [23,33]</td></tr><tr><td>EuroQol 5-Dimensions 5-Levels</td><td>EQ-5D-5L</td><td>Health-related quality of life across five dimensions. Each combination of dimension levels corresponds to a unique health state. Health states are converted into a single index value using a country-specific value set</td><td>5 + VAS</td><td>Mobility</td><td>1-5</td><td>Lower</td><td>3</td><td>0</td><td>-</td><td>42</td><td>23 (54.8%)</td><td>1 [17]</td></tr><tr><td></td><td></td><td></td><td></td><td>Self-care</td><td>1-5</td><td>Lower</td><td>3</td><td>0</td><td>-</td><td>42</td><td>16 (38.1%)</td><td>1 [17]</td></tr><tr><td></td><td></td><td></td><td></td><td>Usual activities</td><td>1-5</td><td>Lower</td><td>3</td><td>0</td><td>-</td><td>42</td><td>35 (83.3%)</td><td>1 [17]</td></tr><tr><td></td><td></td><td></td><td></td><td>Pain/discomfort</td><td>1-5</td><td>Lower</td><td>3</td><td>0</td><td>-</td><td>42</td><td>37 (88.1%)</td><td>1 [17]</td></tr><tr><td></td><td></td><td></td><td></td><td>Anxiety/depression</td><td>1-5</td><td>Lower</td><td>3</td><td>0</td><td>-</td><td>42</td><td>19 (45.23%)</td><td>1 [17]</td></tr><tr><td></td><td></td><td></td><td></td><td>Index</td><td>0-1</td><td>Higher</td><td>0.69</td><td>174</td><td>0.68 [0.36-0.80]</td><td>174</td><td>0.91 [0.79-0.95]</td><td>2 [25,26]</td></tr></tbody></table>
<table><caption>Table 2 (Continued)</caption><thead><tr><th>Instrument</th><th>Abbreviation</th><th>Purpose</th><th>n of questions</th><th>Subitem</th><th>Range values</th><th>Value for favorable</th><th>Cutoff (moderate or higher impact)</th><th>n</th><th>Baseline QoL assessment, pooled<sup>a</sup></th><th>n</th><th>After treatment QoL assessment, pooled<sup>a</sup></th><th>n studies</th></tr></thead><tbody><tr><td>Functional Assessment of Chronic Illness Therapy</td><td>FACIT-Sp-12</td><td>Spiritual well-being in individuals with chronic illness</td><td>12</td><td>VAS</td><td>0-100</td><td>Higher</td><td>70</td><td>246</td><td>38.9 (26.7)</td><td>298</td><td>72.2 (25.8)</td><td>6 [17,21,24-26,33]</td></tr><tr><td>Generalized Anxiety Disorder 7-item scale</td><td>GAD-7</td><td>Severity of anxiety and diagnosis of generalized anxiety disorder</td><td>7</td><td>-</td><td>0-21</td><td>Lower</td><td>10</td><td>72</td><td>5.4 [0.5-10.3]</td><td>9125</td><td>26.9 [20.7-36.7]</td><td>2 [27,33]</td></tr><tr><td>Hospital Anxiety and Depression Scale</td><td>HADS</td><td>States of depression and anxiety in a hospital setting</td><td>14</td><td>Impact question A</td><td>0-3</td><td>Lower</td><td>1</td><td>0</td><td>-</td><td>106</td><td>1 [0-6] &amp; 27/106 (25.5%) ≥ 10</td><td>3 [27,33,34]</td></tr><tr><td>Headache Disability Index</td><td>HDI</td><td>Impact of headaches on daily functioning</td><td>25</td><td>D</td><td>0-21</td><td>Lower</td><td>11</td><td>98</td><td>12.3 (5.0)</td><td>98 &amp; 42</td><td>79/106 (74.5%) ≥ 1</td><td>1 [27]</td></tr><tr><td>Headache Impact Test</td><td>HIT-6</td><td>Impact of headaches on social functioning and quality of life</td><td>6</td><td>-</td><td>36-78</td><td>Lower</td><td>50</td><td>0</td><td>-</td><td>86</td><td>5.8 (3.0) &amp; 16/42 (38.1%) ≥ 11</td><td>3 [17,33,35]</td></tr><tr><td>Monthly Headache Days</td><td>MHD</td><td>Quantify the frequency of headache</td><td>1</td><td>-</td><td>0-30/31</td><td>Lower</td><td>4</td><td>30</td><td>65.3 (9.3)</td><td>314</td><td>45.9 (12.4)</td><td>9 [18,20,23,24,29-31,33,35]</td></tr><tr><td>Migraine Disability Assessment</td><td>MIDAS</td><td>Impact of migraines on daily functioning over the past 3 months</td><td>5</td><td>-</td><td>1 to 4 (grade) or 0-90 (days)</td><td>Lower</td><td>Grade 2 or 10 days</td><td>30</td><td>65.9 [60.9-70.1]</td><td>320</td><td>51.2 [46.1-60.0]</td><td>9 [17-19,26-28,31,33,34]</td></tr><tr><td>Migraine-Specific Quality of Life</td><td>MSQ</td><td>Impact of migraine in role and emotional functioning</td><td>14</td><td>Role function-restrictive; role function-preventive; emotional function</td><td>0-100</td><td>Higher</td><td>50</td><td>29</td><td>47.7 (33.8)</td><td>29</td><td>93.3 (14.6)</td><td>1 [33]</td></tr><tr><td>Neck Disability Index</td><td>NDI</td><td>Self-rated disability in patients with neck pain</td><td>10</td><td>-</td><td>0-50</td><td>Lower</td><td>15</td><td>69</td><td>46.8 (20.3)</td><td>69</td><td>42 (19.2)</td><td>1 [23]</td></tr></tbody></table>
<table><caption>Table 2 (Continued)</caption><thead><tr><th>Instrument</th><th>Abbreviation</th><th>Purpose</th><th>n of questions</th><th>Subitem</th><th>Range values</th><th>Value for favorable</th><th>Cutoff (moderate or higher impact)</th><th>n</th><th>Baseline QoL assessment, pooled<sup>a</sup></th><th>n</th><th>After treatment QoL assessment, pooled<sup>a</sup></th><th>n studies</th></tr></thead><tbody><tr><td>Patient Global Impression of Change</td><td>PGIC</td><td>Overall perception of improvement over time</td><td>1</td><td>-</td><td>1-7</td><td>Higher</td><td>5</td><td>-</td><td>-</td><td>75</td><td>6.3 (1.1)</td><td>2 [18,32]</td></tr><tr><td>Patient Health Questionnaire-9 items</td><td>PHQ-9</td><td>Severity of depression</td><td>9</td><td>-</td><td>0-27</td><td>Lower</td><td>14</td><td>72</td><td>6.2 [3-12.6]</td><td>30 & 106</td><td>2.0 [0-6] & 52 (49.1%)</td><td>3 [27,33,34]</td></tr><tr><td rowspan="3">Patient-Reported Outcomes Measurement System</td><td rowspan="3">PROMIS</td><td rowspan="3">Patient-reported health status across various domains</td><td rowspan="3">Varies</td><td>Physical health</td><td>T-Score Mean Lower 50 (SD 10)</td><td>60</td><td>69</td><td>32 (7)</td><td>69</td><td>35 (7)</td><td>1 [23]</td></tr><tr><td>Mental health</td><td>T-Score Mean Lower 50 (SD 10)</td><td>60</td><td>69</td><td>36.2 (8)</td><td>69</td><td>38 (9)</td><td>1 [23]</td></tr><tr><td>Applied cognition</td><td>T-Score Mean Lower 50 (SD 10)</td><td>60</td><td>69</td><td>40 (7.4)</td><td>68</td><td>40.2 (8.1)</td><td>1 [23]</td></tr><tr><td rowspan="2">Rhodes Index of Nausea, Vomiting, and Retching</td><td rowspan="2">RINVR</td><td rowspan="2">Nausea and vomiting symptoms</td><td rowspan="2">8</td><td>Mental health</td><td>T-Score Mean Lower 50 (SD 10)</td><td>60</td><td>69</td><td>36.2 (8)</td><td>69</td><td>38 (9)</td><td>1 [23]</td></tr><tr><td>Fatigue</td><td>T-Score Mean Lower 50 (SD 10)</td><td>60</td><td>69</td><td>40 (7.4)</td><td>68</td><td>40.2 (8.1)</td><td>1 [23]</td></tr><tr><td>Symptom severity scale</td><td>SSS</td><td>Global symptoms burden</td><td>4</td><td>-</td><td>0-12</td><td>Lower</td><td>4</td><td>42</td><td>5 [3-7]</td><td>-</td><td>-</td><td>1 [34]</td></tr><tr><td rowspan="7">Short Form Health Survey 36 items</td><td rowspan="7">SF-36</td><td rowspan="7">Overall health status and quality of life across eight domains</td><td rowspan="7">36</td><td>Physical functioning</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>45 [30-70]</td><td>1 [27]</td></tr><tr><td>Role functioning/physical</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>0 [0-25]</td><td>1 [27]</td></tr><tr><td>Role functioning/emotional</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>33.3 [0-100]</td><td>1 [27]</td></tr><tr><td>Energy/fatigue</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>20.0 [10-35]</td><td>1 [27]</td></tr><tr><td>Emotional well-being</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>56.0 [42-72]</td><td>1 [27]</td></tr><tr><td>Social functioning</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>37.5 [12.5-68.8]</td><td>1 [27]</td></tr><tr><td>Pain</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>32.5 [16.3-45.0]</td><td>1 [27]</td></tr><tr><td></td><td></td><td>General health</td><td>0-100</td><td>Higher</td><td>74</td><td>0</td><td>-</td><td>95</td><td>35.0 [20.0-52.5]</td><td>1 [27]</td></tr></tbody></table>
<table><caption>Table 2 (Continued)</caption><thead><tr><th>Instrument</th><th>Abbreviation</th><th>Purpose</th><th>n of questions</th><th>Subitem</th><th>Range values</th><th>Value for favorable</th><th>Cutoff (moderate or higher impact)</th><th>n</th><th>Baseline QoL assessment, pooled<sup>a</sup></th><th>n</th><th>After treatment QoL assessment, pooled<sup>a</sup></th><th>n studies</th></tr></thead><tbody><tr><td rowspan="2">Tinnitus Handicap Inventory</td><td rowspan="2">THI</td><td rowspan="2">Impact of tinnitus on 25 daily activities</td><td rowspan="2"></td><td>Physical component</td><td>Standardized Mean 50 (SD 10)</td><td>Higher</td><td>39</td><td>17</td><td>32.8 [20-50]</td><td>112</td><td>33.8 [24.9-67.4]</td><td>2 [27,33]</td></tr><tr><td>Mental component</td><td>Standardized Mean 50 (SD 10)</td><td>Higher</td><td>39</td><td>17</td><td>37.3 [20-57]</td><td>112</td><td>41.5 [31.1-72.2]</td><td>2 [27,33]</td></tr><tr><td>Visual Analog Scale for Pain</td><td>VAS-Pain</td><td>Intensity of pain experienced</td><td>1</td><td>-</td><td>0-10</td><td>Lower</td><td>4</td><td>168</td><td>7.49 (2.0)</td><td>100</td><td>1.44 (2.0)</td><td>3 [18,24,35]</td></tr><tr><td rowspan="2">Widespread Pain Index</td><td rowspan="2">WPI</td><td rowspan="2">Quantify the extent of pain across the body</td><td rowspan="2">19</td><td>-</td><td>0-19</td><td>Lower</td><td>4</td><td>42</td><td>2 [1-4]</td><td>-</td><td>-</td><td>1 [34]</td></tr><tr><td>Work impact</td><td>-</td><td>-</td><td>-</td><td>0</td><td>-</td><td>391</td><td>252 (64.5%)</td><td>5</td></tr><tr><td rowspan="3">Non Standardized 'Self-Declared' Impact [8,17,21,22,27,32]</td><td rowspan="3">N/A</td><td rowspan="3">Impact of condition on daily life</td><td rowspan="3"></td><td>Social impact</td><td>-</td><td>-</td><td>-</td><td>0</td><td>-</td><td>100</td><td>40 (40%)</td><td>2 [8,21]</td></tr><tr><td>Relationship impact</td><td>-</td><td>-</td><td>-</td><td>0</td><td>-</td><td>163</td><td>103 (63.2%)</td><td>3 [8,21,22]</td></tr><tr><td>Emotional impact</td><td>-</td><td>-</td><td>-</td><td>0</td><td>-</td><td>86</td><td>71 (82.6%)</td><td>1 [22]</td></tr></tbody></table>

HRQoL: Health Related Quality Of Life; -: not attributed or not reported.

<footnote>a Results are displayed as mean (SD), median [IQR], in case of frequencies either presence of the condition or 'moderate or higher' impact on QoL (according to the scale interpretation) are reported as n (%). n stands for number(s).</footnote>
<figure><img src="image_4.png" /><figcaption>Fig. 2 – Forest plot: Mean difference meta-analysis for EuroQol 5-Dimension 5-Levels (EQ-5D-5L) visual analog scale (VAS) score. MD: mean difference (Post-Pre); 95% CI: 95% confidence interval; Het: heterogeneity.</figcaption></figure>

<figure><img src="image_5.png" /><figcaption>Fig. 3 – Forest plot of mean difference meta-analysis for head impact test 6 (HIT-6) score. MD: mean difference (Pre-Post); 95% CI: 95% confidence interval; I²: heterogeneity.</figcaption></figure>

on the PHQ-9, and 25.5% demonstrated significant anxiety levels on the GAD-7, with 74.5% indicating that anxiety impacted their ability to work. Goapper et al. reported a significant amelioration of psychological symptoms on HAD-A/D, GAD-7 and PHQ-9 at 3 months following the embolization of CSF-venous fistula [33]. Kapan et al. [22] observed improvements post-treatment using the DASS-21, noting decreases in median scores for depression (from 10 to 6), anxiety (from 6 to 4), and stress (from 14 to 8). Moderate or higher unstandardized impacts on emotional states were also high (82.6%) [22]. Similarly, Volz et al. [25] found that a substantial proportion of patients continued to experience moderate or higher levels of depression (62.8%), anxiety (75.6%), and stress (35.9%) even after treatment. These latest results were reported as long-term outcomes but were assessed only 6 months postoperatively of surgical closure. Cheema et al. [17] also identified considerable psychological morbidity, with 38.1% of patients exhibiting significant anxiety and more than half showing depression on the HADS. Collectively, these findings underscore that SIH profoundly affects patients' mental health, with a notably high prevalence of depression, anxiety, stress, and suicidal ideation.

## 4.8. Social functioning and relationships

Work impact was mostly described by six studies [8,17,21,22,27,32] but without a standardized scale: among 351 patients, 246 individuals (70.1%) reported that the burden of the disease compelled them to take extended leave exceeding three months, alter or adapt their work responsibilities, or quit their jobs entirely. El Rahal et al. [32] described 34/40 (85%) patients ineligible for employment before treatment. From the work of Jesse et al. [8], on average, patients experienced 30 weeks of sick leave and 10.1% retired early. Patients who achieved complete symptom resolution were significantly more likely to return to their previous work patterns (86.8%) compared to those with residual symptoms (56.3%). Similarly, a median score of 0 was reported in the SF-36 role functioning (physical) [27], indicating that 50% of these 95 patients experienced the most severe impact on work or daily activities due to physical health.

In an online questionnaire [17], patients revealed that SIH symptoms often confine them to bed or limit them to less than an hour upright each day, severely impacting daily activities and placing a heavy burden on families, leading to caregiver
<figure><img src="image_6.png" /><figcaption>Fig. 4 – Absolute standardized coefficient graph. This graph shows the impact of different quality-of-life (QoL) assessment tools on patient outcomes, measured as absolute standardized coefficients, sorted from high to low effect. Each bar represents a specific QoL item or scale, with the length of the bar indicating the magnitude of change according to the value of the coefficient at the end of the bars. Used values for calculations are detailed in Supplemental material – Appendix 5. EQ-5D-5L VAS: EuroQol 5-Dimensions 5-Levels Visual Analog Scale; HIT-6: Headache Impact Test-6; DASS-21: Depression Anxiety Stress Scale-21; NDI: Neck Disability Index; THI: Tinnitus Handicap Inventory; PROMIS: Patient-Reported Outcomes Measurement Information System; DHI: Dizziness Handicap Inventory; RINVR: Rhodes Index of Nausea, Vomiting and Retching; 15D Index: 15-Dimension Health-Related Quality of Life Index.</figcaption></figure>

stress, strained family dynamics, career and financial losses, and sometimes forcing them to sell businesses or change living environments. This social burden was also captured with a median of 37.5/(100) considering the social functioning component of SF-36 [27].

## 4.9. Symptom burden and specific conditions

To assess the impact of various symptoms provoked by SIH, eight specific instruments have been employed by three studies, consistently alongside general QoL scales (symptoms

severity scale (SSS) [34], dizziness handicap inventory (DHI) [23,33], headache disability index (HDI) [22], monthly headache days (MHD) [33], widespread pain index (WPI) [34], neck disability index (NDI) [23], Rhodes index of nausea, vomiting and retching (RINVR) [23], tinnitus handicap inventory (THI) [23,33]). Pooled estimates assessed the handicapping effects on daily functioning of dizziness (baseline mean scores of 41.1 (95% CI: 35.6-46.6) in 96 patients), headaches (62.7% of 86 patients experienced moderate to severe disability), neck-related symptoms (baseline mean scores of 46.8 (95% CI: 42.0-51.6) in 69 patients), nausea and vomiting (mean item scores of
1.13 [95% CI: 0.86-1.40] indicating frequent and severe
symptoms), tinnitus (baseline mean scores of 27.2 [95% CI:
21.0-33.5]).

4.10. *Fatigue and energy levels, cognitive function, spiritual well-being*

A first report of the impact of SIH on spirituality using Functional Assessment of Chronic Illness Therapy – Spiritual Well-Being 12 (Facit-Sp-12 [27,33]) was noted. Similarly, research on SIH has not extensively explored neurocognitive deficits and their response to treatment. Caroll et al. described a significant proportion that reported cognitive difficulties before epidural patching and for which treatment led to a substantial improvement [23]. In terms of fatigue, the baseline score was 66.8/100, which slightly reduced to 64.5 after treatment. Another study used the SF-36 energy and fatigue component and found the post-treatment score as low as 20, suggesting fatigue to be considered in the global burden of the disease.

**5. Discussion**

Across multiple domains, our meta-analysis found major
negative impacts on baseline QoL and heterogeneous partial
amelioration after treatment in patients with SIH. We reported
a mean pooled EQ-5D VAS score of 38.9 before and 72.2 after
treatment of SIH with its value being described at 59.7 in
multiple sclerosis [36] and 52.0 in advanced Parkinson disease
[37]. We found a pooled mean HIT-6 score of 66.1 before and
49.3 after treatment, while the mean HIT-6 score is 65.5 in
chronic migraine [38] and 59.7 in idiopathic intracranial
hypertension [39]. While some QoL scales, such as the EQ-
5D-5L and VAS, demonstrate strong responsiveness to
treatment, our study indicates that residual QoL impairments
persist. For example, the SF-36 general health component was
assessed to be low in treated patients (high impact on QoL).
Clinicians should be mindful of residual symptoms and
potential ongoing impact of QoL. These residual effects should
be considered, emphasizing the importance of gathering the
treatment effect on QoL, or evaluating the residual symptoms
on QoL. It is interesting to note that the 15D score improves by
approximately 10% post-procedure yet has about the same
absolute standardized coefficient as DASS-21 stress compo-
nent, considering treatment effect (Fig. 3). Beyond low sample
sizes inflating intervals, high variability in baseline scores or
low sensitivity of measurement scales may explain the
findings. Less sensitive tools might not detect significant
changes in QoL aspects, leading to large raw differences but
low standardized coefficients, especially if scales are broad or
not finely tuned to subtle changes, thus explaining differences
in response sizes or results between scales. Some differences
in samples studied could also confound our results. We
acknowledge heterogenous settings, treatments and symp-
tom durations across studies (Table 1, the duration of
symptoms to the treatment or to the study ranged from 0 to
240 months). A stepwise access for different treatments may
also explain the results of the subgroup analysis (Supplemen-
tal material - Appendix 10), with EBP having the least effect on

QoL. A recent systematic review and meta-analysis compared the efficacy and safety of surgical treatment and transvenous embolization in patients with SIH (therefore limited to CSF-venous fistula), and indicate that both had a comparable efficacy profiles [40]. However, the visual asymmetry found in the funnel plots fitted the distribution of treatment subgroups (Supplemental material – Appendices 6 and 7). Two embolization studies [24,33] reported similarly large QoL improvements and the embolization subgroup showed minimal heterogeneity (I² ≈ 4.6%), since this is analysis is limited to the point that both studies were led by the same group (without overlapping). A similar consideration applies to the surgical subgroup and the two studies led by Volz et al. [25,26].

Changes in QoL among patients with SIH should be carefully evaluated over time due to the disease's complex and heterogeneous presentation, which often overlaps with preexisting long-term symptoms. Acute CSF leaks significantly alter CSF dynamics, but these patterns evolve, and many SIH patients may exhibit normal CSF pressure, explaining that a normal opening pressure does not exclude the diagnosis [41,42]. Symptom duration has been reported as a significant predictor of patient outcomes, with earlier treatment (within 12 weeks) associated with better prognoses (P = 0.013) [43]. Individuals with longer-standing symptoms might not show improvements in generic health-related QoL despite positive clinical responses specific to SIH, which has also been reported in normal pressure hydrocephalus [44]. Post-treatment scores were almost identical in two studies conducted by the same group, where patients were followed for an average of 3 months and 2 years after treatment [8,21], and other authors found that headache intensity remained stable between 3 and 12 months postoperatively [15,25]. These findings highlight the need for strategies to support patients who continue to experience residual symptoms and reduced quality of life [25]. The chronic and long-term repercussions of SIH are yet evident, with a significant portion of patients pooled across the studies unable to work or compelled to take early retirement following the onset of symptoms [2,22]. More than half experienced symptoms persisting over three years, and a considerable number reported a worsening condition over time [42].

A systematic review [45] assessed PROMs' ability to capture the impact of headaches and treatment in adults with chronic or episodic headaches and revealed that three PROMs demonstrated strong evidence for reliability and validity, among them HIT-6. HIT-6 was the most used PROM in our study, which also showed applicability across various headache types and temporal stability. Responsiveness, the ability to detect meaningful change over time, was only partially addressed in the previous review, but we showed that HIT-6 had significant responsiveness to treatment. Along with our study showing that studies equally report different central tendency and dispersion parameters, Haywood et al. [45] highlighted significant heterogeneity in outcome reporting, complicating systematic reviews and meta-analyses.

Given the wide range of symptoms related to SIH, ranging
from headache and dizziness to dementia and even move-
ment disorders [46], the challenge is to assess specific tools for
specific symptoms in SIH and understand the burden of each
symptom on different domains of QoL. Bruce et al. [47] studied
idiopathic intracranial hypertension with mild visual loss, using NEI-VFQ-25 and SF-36 to assess vision-specific and overall health-related QoL. They highlighted symptom-specific improvements and the need for QoL tools tailored to the disease, capturing both direct symptom relief and broader treatment effects. First, we can note that in our report, from the 15 studies that used HIT-6, only 9 (40%) also used another QoL tool. Second, in our context, only one study by Goapper et al. [33] reported the correlation between the change in QoL as a function of headaches, mental factors and symptoms. They have shown that EQ-5D-5L VAS changes was significantly correlated with HIT-6, MSQ and MIDAS changes, but not with SF-36 emotional nor physical components.

Although overlapping with two of our included studies [20,31] Orscelik et al. [48] analyzed nine studies, mainly case series, involving 77 patients. Among these patients, 84.4% reported either complete symptom resolution or marked symptom relief, resulting in significant improvements in QoL. Radiological findings also improved, as seen in the reduced Bern score, which denotes that it also could help in objectively quantifying treatment success, while its correlation with effectiveness and QoL is unclear and should be assessed in further studies. In our review, only 6 of the 16 studies reported the Bern score. The most recent studies found low correlations between clinical headache severity and Bern scores ($\rho$ = 0.139; 95% CI: -0.127 to -0.385) [49].

There is a need for dedicated tools and guidelines to conduct QoL evaluation for patients with SIH. In a recent conference abstract [50], Liaw et al. reported a novel survey instrument for SIH. They distributed their “SIH Impact Inventory” to patients with confirmed or suspected SIH evaluated from 2016 to 2022. Ninety-eight (42%) completed the questionnaires, nearly all participants (96 of 98) had received blood patches, with 44.7% experiencing symptom relief for at least one month and 21.0% achieving full resolution of SIH. In terms of work impact, of those employed, 95.2% (60 of 63) reported difficulties maintaining their jobs due to SIH, and 65.1% (41 of 63) eventually had to leave their employment. Among students, all 18 stated that SIH negatively impacted their attendance and academic performance. SIH also affected transportation and financial stability. While 35.7% indicated that SIH often impaired their ability to drive, 84.7% found it challenging to ride in a car. Financially, 65.3% of participants reported a burden, with most of these costs stemming from medical expenses (98.4%) and travel for healthcare (65.6%). The condition further impacted family life, as 45.9% noted effects on their marriage or romantic relationships, and among parents, 68.8% (48 of 70) said SIH interfered with their parenting abilities. This report aligns with our pooled results.

Qualitative interviews describe the experiences of patients [51] in their daily life, the most disruptive aspects of SIH were the limitations it imposed on daily activities, social interactions, and physical functioning, with patients often needing to restrict their routines to avoid exacerbating symptoms. Many described the challenges of losing independence, missing family activities, and being unable to work, which significantly affected their QoL. Beyond HR QoL, researchers identified multiple life domains [52] that significantly impact QoL, which could be objective (relationships, work, money,

health, and leisure) or subjective (mindfulness, self-esteem, past life events, mental style, and life management). These were partially assessed by our study. A notable percentage of patients reported severe to moderate effects on their relationships, with some cases leading to divorce and ongoing social challenges despite treatment efforts. Work-life is equally affected, with many patients requiring extended sick leave or totally left workforce.

All studies converged to note the significant impact of treatment on SIH-related QoL, but also a strong remaining alteration of QoL in different subdomains. While much improvement occurs post-treatment, persistent psychological challenges remain, highlighting the critical need for ongoing mental health support in the management of SIH. Mental health and fatigue symptoms are missing from many studies of SIH, and yet these symptoms are often not fully corrected by treatment. In many cases, a serious burden of depression and suicidal behavior remains.

This review and meta-analysis have several limitations. First, all included studies were observational (with no randomized trials), and many were retrospective case series, introducing potential selection bias and unmeasured confounding. Second, there was, as demonstrated, considerable high statistical heterogeneity, and the low number of studies in each treatment group limit our subgroup analyses. Third, the outcome assessment was not uniform: studies employed a variety of QoL instruments, and not all domains were consistently evaluated, limiting cross-study comparisons. We pooled the most reported outcomes, but combining pre- vs. post-changes without patient-level data required assumptions (treating changes as independent for lack of paired variance), which may affect precision. Fourth, the possibility of publication bias exists: studies with positive results may be overrepresented and this review was not prospectively registered, which may increase the risk of reporting bias. Finally, generalizability is limited by the fact that most data come from specialized centers.

## 6. Conclusion

Recent years have seen a growing interest in examining QoL in patients with SIH. There is heterogeneity in reporting and use of QoL assessment tools. General health and physical functioning have been the most extensively explored domains, with the EQ-5D-5L (for both) and HIT-6 being the primary assessment tools that also showed high responsiveness to treatment. HIT-6 has also been employed to evaluate treatment effectiveness in previous studies, and we found significant effects among treatments studied. The burden of SIH on Mental Health is the second most reported and pooled results showed significant rates of depression and suicidal behavior. QoL in SIH patients, when untreated, is profoundly impaired across all assessed areas. Treatment interventions have shown significant positive impacts on QoL in SIH, but chronic symptoms of SIH ahead of successful treatment may cause both chronic pre-treatment and chronic residual impacts on various domains of QoL. The variability in study time points and potential recall bias in retrospective studies may affect these outcomes. More comprehensive research is
needed that involves larger patient populations and longitu-
dinal designs to better understand the natural history of QoL in
SIH and the specific effects of actual treatments on different
QoL domains. Additionally, establishing a dedicated evalua-
tion pipeline for QoL, with a tailored series of tests that address
patients' specific symptoms and burdens are underway and
may be essential for advancing the assessment and manage-
ment of QoL in SIH patients.

Availability of data and materials

All data generated or analyzed during this study are included
in this published article and its supplementary information
files.

Declaration of generative AI and AI-assisted
technologies in the writing process

During the preparation of this work the authors used Open AI ChatGPT 4.0 to perform language – English editing. After using this tool, the authors reviewed and edited the content as needed and took full responsibility for the content of the publication.

Author contributions

J.O. writing original draft, data curation, visualization and formal analysis; G.E.H: data curation and formal analysis; S.G.: methodology and formal analysis; J.K.C., A.A.M. and R.K.: writing reviewing and editing; D.F.K. and W.B.: project administration and supervision. All authors reviewed and validated the final version of the manuscript.

Disclosure of interest

J.O. received research grants from the French Society of Neuroradiology SFNR, the French network of University Hospitals HUGO ('Hôpitaux Universitaires du Grand Ouest'), INNOVEO-CHU De Brest, Medtronic, Phenox, Institut Servier, Philippe Foundation, Philips, and receives consulting fees from Balt.

G.E., S.G., J.K.C., A.A.M. declare that they have no
competing interest.

R.K. received research support from Cerenovus Inc, Medtronic, Endovascular Engineering, Frontier Bio, Sensome Inc, Endomimetics, Ancure LLC, Neurogami Medical, MIVI Biosciences, Monarch Biosciences, Stryker, Conway Medical, Piraeus Medical, Rion Inc, and Bionaut Labs. He holds the following research grants: NIH (R01NS076491, R44NS107111, R43NS110114 and R21NS128199) and NSF (081215707).

D.F.K. holds equity in Nested Knowledge, Superior Medical Editors, and Conway Medical, Marblehead Medical and Piraeus Medical. He receives grant support from MicroVention, Medtronic, Balt, and Insera Therapeutics; has served on the Data Safety Monitoring Board for Vesalio, and received royalties from Medtronic.

W.B. holds equity in Nested Knowledge, Superior Medical Editors, Piraeus Medical, Sonoris Medical, and MIVI Neurovascular. He receives royalties from Medtronic and Balloon Guide Catheter Technology. He receives consulting fees from Medtronic, Stryker, Imperative Care, Microvention, MIVI Neurovascular, Cerenovus, Asahi, and Balt. He serves in a leadership or fiduciary role for MIVI Neurovascular, Marblehead Medical LLC, Interventional Neuroradiology (Editor in Chief), Piraeus Medical, and WFITN.

**Appendix A. Supplementary data**

Supplementary data associated with this article can be
found, in the online version, at https://doi.org/10.1016/j.
neurol.2025.08.002.

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