Cluster Headache and Other Trigeminal Autonomic Cephalalgias

Abstract

The trigeminal autonomic cephalalgias are a group of distinct primary headache disorders that share common characteristics of strict unilateral headache often accompanied by unilateral cranial autonomic features. Cluster headache is the most well-known example, but other than neurologists, practitioners often have limited familiarity with these disorders and treatment options. Delays in diagnosis are typical and treatment options remain suboptimal, associated with limited scientific research into these brain disorders. Improved familiarity with core clinical features by health care providers should lead to earlier referral to specialists, and this education is the responsibility of headache medicine specialists. Optimistically, the last few years have seen lobbying for more federal research support in headache medicine and there has been renewed interest by private industry in potential new treatments for trigeminal autonomic cephalalgias.

The first-line cluster headache medication verapamil alters the circadian period and elicits sex-specific sleep changes in mice

“…As the central pacemaker is believed to be primarily responsible for driving behavioral rhythms (Moore and Eichler 1972;Ralph et al 1990;Stephan and Zucker 1972), our results suggest a central action of verapamil consistent with our current understanding of CH as a central nervous system disorder (May et al 2018). The hypothalamus is considered a potential site for the initiation of a cluster headache attack (May et al 2018;McGeeney 2018), and verapamil alters core circadian genes in the hypothalamus (specifically Bmal1, Per1, Per2, Per3, Cry1, and Cry2 in our experiments). In SCN ex vivo slices, however, there was no change in PER2:: LUC reporter oscillations, perhaps due to the exceptionally tight coupling of the SCN clock known to be resistant to genetic and pharmacological manipulation (Chen et al 2012;Liu et al 2007).…”

“…The hypothalamus and cerebellum are central nervous system structures known to have pronounced circadian oscillations and may be important structures in the pathophysiology of cluster headache (Arkink et al 2017;Clelland et al 2014;May et al 1998;Naegel et al 2014;Teepker et al 2012;Yang et al 2015). The trigeminal ganglion is an important peripheral nervous system structure for cluster headache pain (Jarrar et al 2003;May et al 2018;McGeeney 2018), though its circadian oscillations are not well studied. To examine whether verapamil treatment can affect the expression of clock genes in these areas, we measured mRNA expression levels of 10 core clock genes collected at ZT6 and ZT18 from verapamil-treated and control mice (Figure 5).…”

“…Unfortunately, current CH treatments, especially preventive medications, are not particularly effective for many patients: based on patient reports, the most effective preventive treatments are corticosteroids and verapamil, but they are highly effective in only about 50% of the patients (Lademann et al 2015). Due in part to serious side effects of corticosteroids with long-term use, verapamil is considered the first-line preventive medication (May et al 2018;McGeeney 2018). Verapamil is a canonical L-type calcium channel antagonist, though it also affects other calcium channels, sodium channels, potassium channels, and p-glycoprotein (Lemma et al 2006;Tfelt-Hansen and Tfelt-Hansen 2009).…”

A brief diagnostic screen for cluster headache: Creation and initial validation of the Erwin Test for Cluster Headache

“…This fact suggests that the other TACs are an important differential diagnosis to consider when a participant tests positive for our screening tool. However, the possible confounder of other TACs is likely negligible in many settings because paroxysmal hemicrania (30,31), SUNCT/SUNA (32,33), and hemicrania continua (30,34) are even less common than CH (which has a prevalence of 1 in 1000 [35]). A strength of our study is that our validation step included a variety of headache and facial pain disorders: it included 58 participants with diagnoses other than migraine or TACs.…”

“…Second, test-retest reliability was not evaluated. Third, we enrolled a low number of secondary headaches listed in the differential diagnosis of CH, such as tooth impaction, maxillary sinusitis, and headaches due to neoplasms such as pituitary tumors (34). We also did not characterize medication overuse headaches, though in most headache disorders medication overuse headaches do not resemble CH attacks (39).…”