Findings from a clinical trial reported in Headache were unable to show a cause and effect relationship between headache and cerebrospinal fluid (CSF) pressure in idiopathic intracranial hypertension (IIH), despite the fact that headache is generally the first presenting symptom. “You cannot predict the headache disability from the CSF pressure and treating the CSF pressure doesn’t always help the headache,” study co-investigator Deboral L. Friedman, MD, MPH, explained to Neurology Advisor.

Understanding the nature of headache in IIH has been challenging. Dr Friedman, from the department of neurology and neurotherapeutics at the University of Southwestern Texas Medical Center in Dallas, and colleagues found that headache was present at baseline in 84% of participants with newly diagnosed IIH (139 of 165) and mild vision loss in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). The types of headaches varied, including migraine (52%), tension-type (22%), probable migraine (16%), and probable tension-type (4%), with the rest unclassified. Headache locations were equally varied, and mean severity across the cohort was 6.3 on a scale of 0 to 10 (±1.9). Of the participants, 23% reported a headache frequency of 12 or more days per month.

Despite the high rate of comorbidity, the IIHTT investigators found no direct correlation between disability from headache, measured by the Headache Impact Test-6 (HIT-6), and CSF pressure at baseline or 6 months, suggesting that other factors may be involved in the evolution of headache in the presence of IIH. The investigators wrote that “migraine and other headache types may co-exist and be exacerbated by elevated intracranial pressure.”

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An earlier publication of the study in Headache evaluated the secondary benefits of acetazolamide (ACZ) treatment in headache in patients with IIH compared with weight loss and placebo.2 While ACZ therapy improved visual field loss, CSF opening pressure, measures of papilledema, and quality of life in participants with IIH with mild vision loss, it did not improve headache severity.2

Clinically, this suggested that relief of intracranial pressure was not therapeutic for headache, and Dr Friedman noted that “many patients will need concurrent treatment for the intracranial hypertension and the pain.” The IIHTT study group concluded that the current recommendation for CSF pressure reduction therapy to relieve headaches attributed to IIH should be removed from the International Classification of Headache Disorders (ICHD)-3b criteria.3

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Study limitations1,2 included the fact that the investigators relied on patient responses to a questionnaire for headache subtypes and patient-reported comorbidities. There were several problems with quantifying headache days, such as a recall bias, since participants were not asked to keep a calendar, and, more significantly, the questionnaire asked about number of headaches instead of number of headache days, both of which may have resulted in underestimating headache frequency.


  1. Friedman DI, Quiros PA, Subramanian PS, et al. Headache in idiopathic intracranial hypertension: findings from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT)Headache. 2017;57(8):1195-1205.
  2. Smith SV, Friedman DI. The Idiopathic Intracranial Hypertension Treatment Trial: A review of the outcomesHeadache. 2017;57(8):1303-1310.
  3. The International Classification of Headache Disorders, 3rd edition (beta version). Headache Classification Committee of the International Headache Society (IHS). Cephalgia. 2013;33(9):629-808.