Association Between Obstructive Sleep Apnea and Spontaneous Cerebrospinal Fluid Leaks A Systematic Review and Meta-analysis

IMPORTANCE Spontaneous cerebrospinal fluid (CSF) leaks are a morbid condition associated with operative intervention for treatment. Understanding associations are key to diagnosis, treatment, and possible early detection. OBJECTIVE To determine the clinical association and odds of having obstructive sleep apnea (OSA) and spontaneous CSF leaks. DATA SOURCES A comprehensive search of the literature was conducted using PubMed (MEDLINE), Cochrane Library, and relevant article bibliographies. STUDY SELECTION Systematic review and meta-analysis of studies from 2005 to 2015 investigating spontaneous CSF leaks in patients with OSA. The CSF leaks were considered spontaneous when they occurred in the absence of trauma, surgery, infection, and neoplasm. Included studies provided the number of patients diagnosed as having OSA and spontaneous CSF leaks. DATA EXTRACTION AND SYNTHESIS Two independent investigators reviewed all studies for inclusion. The numbers of patients with OSA were systematically extracted from each study. Studies that compared the prevalence of OSA with spontaneous CSF leaks against their control cohort were pooled in the meta-analysis using a random-effects model. MAIN OUTCOME AND MEASURE To determine whether there was increased incidence of OSA in patients with spontaneous CSF leaks. This hypothesis was formulated prior to data collection. RESULTS The search criteria yielded 384 abstracts, and 6 clinical studies involving OSA and CSF leaks met the inclusion and exclusion criteria. They were all retrospective in nature and included 3 comparative (case-control) studies, 2 case series, and 1 case report. The cumulative reported prevalence of having OSA and spontaneous CSF leaks is 16.9%(232 of 1376 patients). Three of the studies were eligible for the meta-analysis. The odds of having OSA with a spontaneous CSF leak were 4.73 times more likely than in control cohorts (95% CI, 1.56-14.31; P = .006; I-2 = 35%). In a subgroup analysis of studies including nonspontaneous CSF leaks as their control cohort, the odds of having OSA with a spontaneous CSF leak were 2.85 times more likely than OSA with a nonspontaneous CSF leak (95% CI, 1.22-6.63; P = .02; I-2 = 0%). There was a notable difference in the age, BMI, or patients with hypertension in the comparative studies. CONCLUSIONS AND RELEVANCE The association between OSA and spontaneous CSF leaks as demonstrated by retrospective studies is confounded by heterogeneous patient characteristics. Large prospective controlled studies using polysomnography and elevated intracranial pressure measurements are required to further evaluate the relationship between OSA and spontaneous CSF leaks.