by Deborah I. Friedman, MD, MPH, FAAN, FAHS

Idiopathic intracranial hypertension, also known as the pseudotumor cerebri syndrome, affects 25/100,000 obese women of childbearing age. Although the feared complication is permanent visual loss or even blindness, headache is the most common symptom and the largest contributor to reduced quality of life in these patients [1].

Many patients with Idiopathic Intracranial Hypertension (IIH) continue to have headaches after their intracranial pressure is well controlled, the papilledema resolves and the disorder is otherwise in remission. The headaches in these patients are frequently quite treatment-resistant. The pathogenesis of the persistent headache disorder is uncertain but may be related to trigeminal central sensitization induced by the effect of increased intracranial pressure on pain-sensitive structures in the head. 

The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) was a randomized trial studied 165 participants (161 women) with newly-diagnosed IIH to assess the effect of ACTZ compared to PBO on visual function [2]. 40% of enrollees self-reported a prior history of migraine. Although the IIHTT did not investigate a correlation between prior migraine and headache disability, the high prevalence of migraine in this cohort was striking (more than double the expected population rate). Because the headache phenotype of IIH most commonly resembles migraine [3], there is rationale to implicate calcitonin gene-related peptide in its pathophysiology.

To date, there has not been a prospective study or even large retrospective study to investigate the outcome of various headache therapies on persistent or chronic IIH-related headache. Many preventive medications are used in practice, including topiramate, zonisamide, tricyclic antidepressants, SSRIs, SNRIs, beta blockers and onabotulinumtoxinA.  However, the potential benefit of preventive treatment must be weighed against potential side effects that could cause a recurrence of IIH, the most important of which is weight gain. These considerations limit the options for many of the oral headache preventive treatments. The anti-CGRP monoclonal antibodies offer the possibility of reducing headache frequency and severity in patients with previous IIH and are well-tolerated overall.

The results of this study, if positive, could be used to influence practice and for further research. If a benefit is seen, a prospective study, possibly with an active comparator, would provide more valuable insight into forming best practices. A negative result would be equally informative, as practitioners would be less likely to prescribe the anti-CGRP monoclonal antibodies, which are relatively expensive, for the treatment of these patients.

 

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References

1. Digre KB, Bruce BB, McDermott MP et al. Quality of life in idiopathic intracranial hypertension at diagnosis: IIH Treatment Trial results.  Neurology 2015;16:2449-56
2. Wall M, McDermott MP, Kieburtz KD et al. Effect of acetazolamide on visual function in patients wtih idiopathic intracranial hypertension and mild visual loss. JAMA Neurol 2014;13:1641-51
3. Friedman DI, Quiros P, Subramanian P et al.  Headache characteristics and outcomes in the Idiopathic Intracranial Hypertension Treatment Trial. Headache 2017;57:1195-1205