Erenumab for headaches in idiopathic intracranial hypertension: A prospective open‐label evaluation

Wakerley

et al. 2021

Life

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Migraine is a highly prevalent and disabling primary headache disorder, however its pathophysiology remains unclear, hindering successful treatment. A number of key secondary headache disorders have headaches that mimic migraine. Evidence has suggested a role of mitochondrial dysfunction and an imbalance between energetic supply and demand that may contribute towards migraine susceptibility. Targeting these deficits with nutraceutical supplementation may provide an additional adjunctive therapy. Neuroimaging techniques have demonstrated a metabolic phenotype in migraine similar to mitochondrial cytopathies, featuring reduced free energy availability and increased metabolic rate. This is reciprocated in vivo when modelling a fundamental mechanism of migraine aura, cortical spreading depression. Trials assessing nutraceuticals successful in the treatment of mitochondrial cytopathies including magnesium, coenzyme q10 and riboflavin have also been conducted in migraine. Although promising results have emerged from nutraceutical trials in patients with levels of minerals or vitamins below a critical threshold, they are confounded by lacking control groups or cohorts that are not large enough to be representative. Energetic imbalance in migraine may be relevant in driving the tissue towards maximum metabolic capacity, leaving the brain lacking in free energy. Personalised medicine considering an individual’s deficiencies may provide an approach to ameliorate migraine.

Section: Headache Mechanismsmentioning

confidence: 68%

Section: Headache Mechanismsmentioning

confidence: 99%

The Role of Metabolism in Migraine Pathophysiology and Susceptibility

Wakerley

et al. 2021

Life

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“…In adults, headache features often resemble those with primary headache disorders 15 . When phenotyping headache in IIH recurrent episodes of headache may vary considerably in terms of frequency, duration, and pain intensity 15,16,19 . In a large trial, IIH headache was described as pressure‐like in 47% and throbbing in 42% 15 .…”

Section: Methodsmentioning

confidence: 99%

Headache attributed to idiopathic intracranial hypertension and persistent post‐idiopathic intracranial hypertension headache: A narrative review

2021

Headache

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Objective Headache is a near‐universal sequela of idiopathic intracranial hypertension (IIH). The aim of this paper is to report current knowledge of headache in IIH and to identify therapeutic options. Background Disability in IIH is predominantly driven by headache; thus, headache management is an urgent and unmet clinical need. At present, there is currently no scientific evidence for the directed use of abortive or preventative headache therapy. Methods A detailed search of the scientific literature and narrative review was performed. Results Headache in IIH is driven by raised intracranial pressure (ICP) and reduction of ICP has been reported in some studies to reduce headache. Despite resolution of papilledema and normalization of raised ICP, a majority suffer persistent post‐IIH headache. The lack of evidence‐based management approaches leaves many untreated. Where clinicians attempt to manage IIH headache, they use off‐label therapies to target the prevailing headache phenotype. A recent prospective open‐label study demonstrated the effective use of a calcitonin gene‐related peptide monoclonal antibody therapy in IIH for persistent post‐IIH headache. Conclusions There is overwhelming evidence of the headache burden in IIH. Studies are required to investigate the biological foundations of headache related to ICP and to develop treatments specifically directed to manage headache in IIH.

“…As the phenotype of raised ICP headache is for some not classically an early morning headache [ 74 ], but can mimic migraine, future studies may investigate the utility of mainstream headache medications for management [ 4 , 75 ]. Indeed, discoveries of therapies for headache attributable to IIH also require systematic evaluation, as there is only one open label study investigating use of a calcitonin gene related peptide monoclonal antibody to treat headache in patients with active IIH [ 76 ]. What was interesting was that a small subset of patients had reoccurrence of their papilloedema without a return of their headache symptoms, which may implicate CGRP in the underlying pathways causing headache [ 77 ].…”

Section: Management Of Iihwopmentioning

confidence: 99%

Current Perspectives on Idiopathic Intracranial Hypertension without Papilloedema

Chong

et al. 2021

Life

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The pseudotumor cerebri syndrome embraces disorders characterised by raised intracranial pressure, where the commonest symptom is headache (90%). Idiopathic intracranial hypertension without papilloedema (IIHWOP) is increasingly recognised as a source of refractory headache symptoms and resultant neurological disability. Although the majority of patients with IIHWOP are phenotypically similar to those with idiopathic intracranial hypertension (IIH), it remains uncertain as to whether IIHWOP is nosologically distinct from IIH. The incidence, prevalence, and the degree of association with the world-wide obesity epidemic is unknown. Establishing a diagnosis of IIHWOP can be challenging, as often lumbar puncture is not routinely part of the work-up for refractory headaches. There are published diagnostic criteria for IIHWOP; however, some report uncertainty regarding a pathologically acceptable cut off for a raised lumbar puncture opening pressure, which is a key criterion. The literature provides little information to help guide clinicians in managing patients with IIHWOP. Further research is therefore needed to better understand the mechanisms that drive the development of chronic daily headaches and a relationship to intracranial pressure; and indeed, whether such patients would benefit from therapies to lower intracranial pressure. The aim of this narrative review was to perform a detailed search of the scientific literature and provide a summary of historic and current opinion regarding IIHWOP.