CLUSTER HEADACHE AND RELATIVES

Indescribable faceache
Drawing of I. Rubloff entitled "indescribable faceache". (c) 2005, I. Rubloff, all rights reserved

 

Timothy C. Hain, MD • Page last modified: May 13, 2021

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Cluster headache is defined as excruciating unilateral head pain which occurs in brief episodes (15 minutes-2 hours). Clusters consist of headache that occur daily for 3 weeks to 3 months, then remit. Typically there are bouts in early July and early January. Thus cluster headaches are seasonal, and sometimes can be associated with other seasonal illnesses such as seasonal vertigo.

Cluster may awaken one from sleep (migraine and tension usually won't). Some experience flushing, droopy eye, nasal stuffiness, or eye tearing. Clusters are typically "side locked". They do not alternate sides. Men are affected 2 to 5 times more frequently than are women (reverse of migraine). Unlike the situation for migraine, menopause does not reduce the frequency and severity of headache in women. Perhaps related, attaining an advanced age does not reduce the frequency of cyclic vomiting either, which is treated somewhat similarly. There probably are several mechanisms for same symptom complex - migraine variant, sphenopalatine neuralgia, and perhaps a genetic syndrome involving circadian rhythms. Cluster headache is weakly inherited with about 5.4% of identical twins both having cluster (Waung et al, 2020). Like migraine in general, there appears to be multiple susceptibility genes, suggesting that it is not a homogeneous entity.

The reason for the peculiar periodicity of cluster headache has recently been discussed (Pringsheim T, 2002). There are two genes -- the PER or period gene located on the X chromosome and the timeless (TIM) gene. Both genes affect the suprachiasmatic (STC) nucleus of the hypothalmus. These genes generate products that control circadian rhythms. It seems reasonable to hypothesize that in cluster headache there is a disturbance of this clock.

Related headaches -- "TAC" or trigeminal autonomic cephalgias

Headaches with droopy eyelids on one side, or perhaps just red eyes on one side, are now usually attributed one of a family of headache syndromes called the trigeminal autonomic cephalgias (TACs). TACs are characterized by unilateral trigeminal nerve distribution pain that occurs in tandem with ipsilateral cranial nerve autonomic symptoms. The TACs include paroxysmal hemicrania, cluster headache, hemicrania continua, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) (Bodle and Emmady 2021). One wonders how the droopy eye and ptosis (which is not controlled by the trigeminal nerve), can be compatable with the term "TAC", although TAC is pithy and easy to remember.

All of these named variants are basically the result of "splitting", as practically while one can recognize a TAC from the droopy eye and unilateral symptoms, one still has to try out various medications as these headaches are very severe. The "lumper/splitter" problem has been discussed by Russo, A., et al. (2019).

Paroxysmal hemicrania (PH)

Paroxysmal hemicrania (PH) is similar to cluster. Both disorders are short-lived, unilateral, and accompanied by ipsilateral autonomic features. The PH patients show a female predominance, a shorter attack duration (2-30 min), and often a greater attack frequency (5 or more/day). A prompt response to indomethacin with this symptom complex confirms the diagnosis of PH, according to Lipton (Lipton et al, 2003) The name "Paryxosymal Hemicrania" seems a bit vague to us, as it translates into intermittent head pain. Perhaps an acronym that includes indomethasin responsiveness would be better -- IRPH ? or maybe IRP ? It is pithy anyway.

Other medications than indomethacin ? largely migraine treatments -- have been tried with varying success in PH including topiramate (Camarda, Camarda, and Monastero 2008),verapamil (Evers and Husstedt 1996) (Shabbir and McAbee 1994), sumatriptan (Hannerz and Jogestrand 1993) (Antonaci et al. 1998) oxygen (mainly for cluster) (Heckl 1986), Celebrex (Mathew, Kailasam, and Fischer 2000), acetazolamide (Warner, Wamil, and McLean 1994), lithium or valproate (Brandt, Paulus, and Pollmann 1991). In other words, almost the entire migraine repertoire has been tried with some success in PH, as well as unusual drugs such as oxygen and lithium. Sphenopalatine nerve blocks are reserved for "refractory" PH. (Morelli et al. 2010), sphenopalatine nerve stimulation is reported effective, again in refractory cluster (Fontaine, Santucci, and Lanteri-Minet 2018).

SUNCT -- "short-lasting unilateral neuralgiform headache attacks with conjunctival injection"

Continuing the discussion of other headaches split off from cluster, SUNCT is yet another headache sharing most of the characteristics of cluster, and having a very similar responsiveness to migraine medications as well as sphenopalatine nerve stimulation (Lambru et al, 2021).

Acute Treatment of Cluster:

Returning to cluster, these  headaches are extremely painful and the author's present practice is to use multiple medications simultaneously when it recurs. The author's usual protocol is to combine a triptan (injection or nasal spray) with steroids and verapamil for prevention.  The triptans are used for pain control, while waiting for the steroids and verapamil to take effect. McGeeney comments that injection, inhalation and nasal spray therapies are superior to oral treatment for acute treatment of cluster headache. The new family of CGRP inhibitors, may be a good idea for cluster at the onset, as they seem to work and also they last about a month.

Below are acute treatments reported in the literature.

A new approach to acute cluster was reported by Khatami et al.  Xyrem (Sodium oxybate), which induces extremely deep sleep, was reported to be effective in cluster(2011).  It is our thought that as clusters normally occur in the middle of the night, someone on Xyrem might simply sleep through them.  This seems to us to be potentially a better way of managing them than many of the medications above. Xyrem, however, has major barriers to obtaining a rapid prescription.

Butorphanol nasal spray is best avoided due to alarming rates of abuse, addiction and even death McGeeney (2019).

Prevention of cluster headache

There are a number of peculiar treatments such as Civamide (related to hot peppers), Warfarin (a blood thinner) that we advise against. The protocol here aims for an INR between 1.5-1.9. There have also been some limited reports of utility for antiepileptic migraine medications such as topiramate, gabapentin and sodium valproate. We do not think that invasive treatment such as use of simulators are reasonable in any but the persons who have failed all else.

References: