Cluster headache, characterized by severe, recurrent unilateral headache attacks and ipsilateral autonomic cranial symptoms, is today still a primary headache whose pathophysiology is poorly understood, even if we know that it There is a close interrelationship between genetics, smoking and sex hormones. While its symptoms are similar globally, regional differences in prevalence and burden are noted.
The discovery of effective treatments has broadened the understanding of this pathology, in particular through the identification of eight genetic loci. Additionally, targeting the autonomic trigeminal reflex through neurostimulation, or targeting calcitonin gene-related peptide (CGRP), could reduce the impact of pain attacks.
Currently, the European Academy of Neurology (EAN) recommends 100% oxygen therapy in the acute phase with a flow rate of at least 12 L/min for 15 min associated with 6 mg of sumatriptan SC. Prophylaxis of cluster headache attacks with verapamil at a daily dose of at least 240 mg is also recommended, combined with corticosteroids at a minimum dose of 100 mg prednisone orally (up to 500 mg IV /day) for 5 days as a relay treatment.
Lithium, topiramate and galcanezumab (only for episodic cluster headaches), or even valproic acid or melatonin, are alternatives while non-invasive stimulation of the vagus nerve is effective in episodic headaches but not when they are chronic.
Finally, while superior occipital nerve block is recommended, electrical stimulation is not due to side effects. Furthermore, a block of the greater occipital nerve with corticosteroids combined with lidocaine has shown great possibilities and makes it possible to reduce the doses of verapamil.
However, studies have shown a risk of seizures switching to the side not previously affected, without knowing the reason. Regardless, researchers still need to determine whether the effect of neuromodulation is related to an anti-inflammatory effect or a central action.
A strong involvement of smoking
Genetically correlated with smoking, risky behaviors, attention deficit hyperactivity disorder, depression and musculoskeletal pain, cluster headache was the subject of a first meta-analysis of genome-wide association in ways that provide clues to its biological basis.
The estimated heritability of cluster headache based on SNPs was 14.5%, while the authors identified 9 independent signals in 7 genome-wide significant loci in the primary meta-analysis, and an additional locus in the trans-ethnic meta-analysis. Five of these loci were already known.
Finally, the 20 genes identified as potentially causal for cluster headaches showed enrichment in arteries and brain tissue. Mendelian randomized analysis also indicated a causal effect of smoking intensity on cluster headache. Three of the loci identified were associated with migraine.
The link with smoking is therefore obvious, concludes Rolf Fronczek (Leiden, Netherlands), which is supported by the observation of a very high prevalence of tobacco users and parental smoking in patients suffering from cluster headaches. However, while early work suggested that stopping smoking did not reduce seizure frequency, a recent population study demonstrated the opposite.
There is still a lot of work left, he concludes, in particular to determine why the hypothalamus is dysfunctional (to trigger the seizure or to shift the seizures to the unaffected side in the case of greater occipital block), but also to know the role sexual hormones (hypogonadism is frequently found), the role of sleep and that of the biological clock suggested by the presence of mutations in the genes which regulate it, the role of vasoactive substances and the importance of epigenetics.
