Cluster headache pathophysiology — insights from current and emerging treatments

Wei, Diana Y.; Goadsby, PJ

doi:10.1038/s41582-021-00477-w

Cited by 60 publications

(91 citation statements)

References 236 publications

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“…Imaging studies provided evidence of network disruption and altered hypothalamic functional connectivity that back the idea of multifactorial disease [146]. Likewise, the effect of acute and preventive medication provides insights into the pathophysiology of the disorder [147]. However, these studies did not indicate where these alterations add together to trigger an attack.…”

Section: Discussionmentioning

confidence: 99%

Cluster Headache Pathophysiology—A Disorder of Network Excitability?

Pohl

Sándor

Michels

et al. 2021

CTN

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Patients’ accounts of cluster headache attacks, ictal restlessness, and electrophysiological studies suggest that the pathophysiology involves Aδ-fibre nociceptors and the network processing their input. Continuous activity of the trigeminal autonomic reflex throughout the in-bout period results in central sensitization of these networks in many patients. It is likely that several factors force circadian rhythmicity upon the disease. In addition to sensitization, circadian changes in pain perception and autonomic innervation might influence the excitability of the trigeminal cervical complex. Summation of several factors influencing pain perception might render neurons vulnerable to spontaneous depolarization, particularly at the beginning of rapid drops of the pain threshold (“summation headache”). In light of studies suggesting an impairment of short-term synaptic plasticity in CH patients, we suggest that the physiologic basis of CH attacks might be network overactivity—similarly to epileptic seizures. Case reports documenting cluster-like attacks support the idea of distinct factors being transiently able to induce attacks and being relevant in the pathophysiology of the disorder. A sustained and recurring proneness to attacks likely requires changes in the activity of other structures among which the hypothalamus is the most probable candidate.

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Section: Discussionmentioning

confidence: 99%

Cluster Headache Pathophysiology—A Disorder of Network Excitability?

Pohl

Sándor

Michels

et al. 2021

CTN

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“…11 This framework provides a rationale for the use of interventional therapies in HC. 12 Symptomatic improvement has been observed after sphenopalatine ganglion blockade and non-invasive vagus nerve stimulation, perhaps via modulation of the trigeminal-autonomic reflex. 5 6 13 In a cross-over study of six patients receiving occipital nerve stimulation, a branch of the C2 nerve root, five patients reported significant symptom improvement.…”

Section: Discussionmentioning

confidence: 99%

Temporary resolution of hemicrania continua following ipsilateral ear piercing

Bryson

2021

BMJ Neurol Open

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BackgroundHemicrania continua is an uncommon subtype of trigeminal autonomic cephalgia that exhibits dramatic therapeutic response to indomethacin. Unfortunately, indomethacin is associated with a range of adverse effects, including neuropsychiatric complications, which limits its use in many patients. Although no other effective pharmacologic agents exist, there is emerging evidence for interventional treatments such as occipital nerve and vagus nerve stimulation, which may act by modulating neural activity within the trigeminovascular system.CaseWe present a 30-year-old woman with long-standing refractory hemicrania continua who suffered adverse effects to indomethacin. She experienced temporary, but near-complete, symptom resolution following piercing of the crus of the ear helix ipsilateral to her headache, whereas contralateral piercing produced no benefit.ConclusionsTo our knowledge, this case is the first to describe a therapeutic benefit following ear piercing in a patient with trigeminal autonomic cephalgia. We argue that symptom relief was obtained through a similar mechanism to occipital or vagus nerve stimulation.

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“…The pathogenesis of this disease is, at the current state of knowledge, based on the derangement of the complex interactions existing between the trigeminovascular system activating the trigeminal-autonomic reflex, leading to the release of specific neuropeptides like calcitonin gene-related peptides (CGRP) and pituitary adenylate cyclase-activating polypeptide 38 (PACAP-38), and its interactions with a deranged (putative) hypothalamic control center [5,6]. Further multiple basic and clinical research approaches have added important information on the role of neurosteroids, neuroimaging and neurophysiology data, sleep disorders, and psychiatric comorbidities in this still not completely clear pathophysiological picture of CH [7][8][9][10].…”

Section: Cluster Headache the Cinderella Among The Primary Headachesmentioning

confidence: 99%

Cluster Headache is Still Lurking in the Shadows

Martelletti

Curto

2021

Pain Ther

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Cluster headache, apart from its legendary reputation as the most violent headache that can exist, suffers from an average 60-month delay in diagnosis. The simplicity of the clinical manifestations, although dramatic, makes this delay inexplicable. The education of emergency department physicians and various specialists not specifically dedicated to headaches allows cluster headache to remain in a lurking position with flourishing periods of disease that are often unpredictable in both onset and disappearance.Older drugs have always shown high efficacy but also an equally high rate of adverse events, often discouraging their appropriate use. The availability of a new drug class such as monoclonal antibodies for calcitonin gene-related peptide or its receptor (CGRP (r) ), which have already been efficient for migraine, shows a jeopardized geography of access in the world, and this favors the progression of the episodic form into chronic and of the chronic into refractory.

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Cluster headache pathophysiology — insights from current and emerging treatments

Cited by 60 publications

References 236 publications

Cluster Headache Pathophysiology—A Disorder of Network Excitability?

Cluster Headache Pathophysiology—A Disorder of Network Excitability?

Temporary resolution of hemicrania continua following ipsilateral ear piercing

Cluster Headache is Still Lurking in the Shadows

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