PURPOSE OF REVIEW: Headache disorders attributed to low and high intracranial pressure are commonly encountered in specialty headache practices and may occur more frequently than realized. While the headaches resulting from intracranial pressure disorders have what are conventionally thought of as defining characteristics, a substantial minority of patients do not manifest the “typical” features. Moreover, patients with intracranial pressure disorders may also have a preexisting primary headache disorder. Heightening the complexity of the presentation, the headaches of intracranial pressure disorders can resemble the phenotype of a primary disorder. Lastly, patients with so-called intracranial “hypotension” often have normal CSF pressure and neuroimaging studies. Thus, a high index of suspicion is needed. The published literature has inherent bias as many types of specialists evaluate and treat these conditions. This article reviews the key points to emphasize the history, examination, and laboratory evaluation of patients with intracranial pressure disorders from a neurologist’s perspective.

RECENT FINDINGS: Lumbar puncture opening pressure in patients with spontaneous intracranial hypotension was low enough to meet diagnostic criteria (≤60 mm CSF) in only 34% of patients in one study. Most patients had an opening pressure in the low normal to normal range, and 5% had an opening pressure of 200 mm CSF or more. Diskogenic microspurs are a common cause of this syndrome. The Idiopathic Intracranial Hypertension Treatment Trial found that most participants had a headache phenotype resembling migraine or tension-type headache. No “typical” or characteristic headache phenotype was found, and headache-related disability was severe at baseline. Headache disability did not correlate with the lumbar puncture opening pressure at baseline or at the 6-month primary outcome period. Although participants who were randomly assigned to acetazolamide had a lower mean CSF opening pressure at 6 months, headache disability in that group was similar to the group who received placebo.

SUMMARY: Significant overlap is seen in the symptoms of high and low CSF pressure disorders and in those of primary headache disorders. Neurologists are frequently challenged by patients with headaches who lack the typical clinical signs or imaging features of the pseudotumor cerebri syndrome or spontaneous intracranial hypotension. Even when characteristic symptoms and signs are initially present, the typical features of both syndromes tend to lessen or resolve over time; consider these diagnoses in patients with long-standing “chronic migraine” who do not improve with conventional headache treatment. While the diagnostic criteria for pseudotumor cerebri syndrome accurately identify most patients with the disorder, at least 25% of patients with spontaneous intracranial hypotension have normal imaging and over half have a normal lumbar puncture opening pressure. Detailed history taking will often give clues that suggest a CSF pressure disorder. That said, misdiagnosis can lead to significant patient morbidity and inappropriate therapy.

Address correspondence to Dr Deborah I. Friedman, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, MC 9322, Dallas, TX 75390, Deborah.Friedman@UTSouthwestern.edu.

RELATIONSHIP DISCLOSURE: Dr Friedman has received personal compensation for serving on the advisory boards of Alder BioPharmaceuticals, Inc; Amgen Inc; Avanir Pharmaceuticals, Inc; Biohaven Pharmaceutical; ElectroCore, LLC; Supernus Pharmaceuticals, Inc; Teva Pharmaceutical Industries Ltd; and Zosano Pharma Corporation. Dr Friedman has received personal compensation for serving on the board of directors of the American Headache Society, as a contributing author for MedLink Neurology, and on the editorial board of Neurology Reviews. Dr Friedman has received personal compensation as a consultant for Avanir Pharmaceuticals, Inc; Biohaven Pharmaceutical; ElectroCore, LLC; Eli Lilly and Company; Promius Pharma, LLC; and Teva Pharmaceutical Industries, Ltd and as a speaker for Allergan; Amgen Inc; Avanir Pharmaceuticals, Inc; ElectroCore, LLC; Supernus Pharmaceuticals, Inc; and Teva Pharmaceutical Industries, Ltd. Dr Friedman has received research/grant support from Autonomic Technologies, Inc; Axon Optics; Eli Lilly and Company; Merck & Co, Inc; and Zosano Pharma Corporation. Dr Friedman has served as an expert witness in legal cases involving idiopathic intracranial hypertension.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Dr Friedman discusses the unlabeled/investigational use of acetazolamide for the treatment of pseudotumor cerebri syndrome, the use of gadolinium for MRI myelography for the diagnosis of spontaneous intracranial hypotension, and the use of zonisamide for the treatment of associated headache.

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