CLUSTER HEADACHE AND RELATIVES
|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.
- Analgesics -- rarely effective, even narcotics.
- Indomethacin (25 TID) -- response to indomethacin suggests the diagnosis name should be changed to paroxysmal hemicrania.
- Intranasal Capsaicin. While effective for prevention, this is difficult to administer.
- Ergot and related medications including triptans.
- Ergot compounds and triptans work but may be addictive in this syndrome
due to rebound and requirements for frequent administration. Would start with
these anyway, as need a fast acting agent. The most effective agent is subcutaneous 6mg sumatriptan. According to McGeeny, SC sumatriptan and zolmatriptan nasal spray are the "premier abortive therapies" for cluster.
- Nasal DHE can be used and appears to be useful. Howver, there are better agents.
- Sumatriptan -- might differentiate migraine from neuralgia. Intranasal is the most effective method (Markey, 2003). Injectable is
the most reliable method. See also Hardebo, 1998. Oral triptans are unsuitable. Sumatriptan nasal spray is not nearly as good as the injectable method (McGeeney, 2019). Sumatriptan might be more suitable for use during the day, when an oxygen tank is not available.
- Zolmatriptan nasal spray (Markey, 2003). According to McGeeney, 6 mg of injectable sumatriptan works more quickly than zolmitriptan nasal spray.
- DHE-45 (Intranasal), or via an intravenous protocol. While this may work, there are better choices.
- Intranasal lidocaine. A 4% solution administered by drops (not spray) has been reported successful. (Markey 2003). This must be compounded as there is no commercial product.
- Oxygen (5-15 L flow x 10 min) also reportedly works in 50%.. According to McGeeney (2019), there is strong evidence for high-flow oxygen. He recommends 15 L/min via a nonbreather mask, to be administered for 15-20 minutes as soon as an attack begins. Oxygen concentators generally have a lower flow rate (1-5 L/min). A 15 L/min flow rate requires a supplier to provide a regulator that is higher than used for cardiopulmonary disease. Sometimes a "demand valve" such as used by divers is used. Welding oxygen is not inherently dangerous but is not as safe as medical oxygen (McGeeney, 2019).
- Steroids (Decadron 0.75 BID x 7 D). Other authors recommend prednisolone
(Bahra et al, 2002). Injections into the occipital area have also had some success, but this does not appear to be well documented.
- Surgical treatments
- Trigeminal nerve section -- can be used in intractable chronic cases (Jarrar
et al, 2003). We have never encountered this.
- Occipital nerve stimulation (Burns, 2009). Used in intractable cases.
- Vagus nerve stimulation (Nesbitt et al, 2015). Needs much more study.
- Xyrem (sodium oxybutate)
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
- Lithium -- equivalent to verapamil in efficacy, but more side effects (Bussone et al, 1990). One trial reported using 300 mg 3 times/day, with 50% reduction after 2 weeks.
- Melatonin, in a dose of 10 mg every evening, was reported to stop attacks in 50% afte 5 days. (Schindler and Gottschalk, 2019) Some report using as much as 30 mg.
- Verapamil (Calan) prophylaxis often works (Schindler and Gottschalk, 2019) , but may be too slow in onset
(2 week) to be useful acutely. Verapamil works best in large doses -- 240 to 480/day. When used in this dose, heart monitoring is suggested. (Blau et al, 2004; Bussone et al, 1990; Cohen et al, 2007).
- The CGRP antagonists may be especially potent in Cluster.
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.
- Bahra, A., et al. (2002). "Cluster headache: a prospective clinical study
with diagnostic implications." Neurology 58(3): 354-61.
- Blau JN. and H. O. Engel (2004). "Individualizing treatment with verapamil for cluster headache patients." Headache 44(10): 1013-8.
- Bodle, J., and P. D. Emmady. 2021. 'Chronic Paroxysmal Hemicrania.' in, StatPearls (Treasure Island (FL)).
- Brandt, T., W. Paulus, and W. Pollmann. 1991. '[Cluster headache and chronic paroxysmal hemicrania: current therapy]', Nervenarzt, 62: 329-39.
- Burns B, Watkins L, goadsby P. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients. Neurology 2009:72:341-345
- Bussone, G et al. (1990). "Double blind comparison of lithium and verapamil in cluster headache prophylaxis." Headache 30(7): 411-7.
- Camarda, C., R. Camarda, and R. Monastero. 2008. 'Chronic paroxysmal hemicrania and hemicrania continua responding to topiramate: two case reports', Clin Neurol Neurosurg, 110: 88-91.
- Cohen AS et al. (2007). "Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy." Neurology 69(7): 668-75.
- Evers, S., and I. W. Husstedt. 1996. 'Alternatives in drug treatment of chronic paroxysmal hemicrania', Headache, 36: 429-32.
- Fontaine, D., S. Santucci, and M. Lanteri-Minet. 2018. 'Managing cluster headache with sphenopalatine ganglion stimulation: a review', J Pain Res, 11: 375-81.
- Hannerz, J., and T. Jogestrand. 1993. 'Intracranial hypertension and sumatriptan efficacy in a case of chronic paroxysmal hemicrania which became bilateral. (The mechanism of indomethacin in CPH)', Headache, 33: 320-3.
- Hardebo JE, Dahlof C. Sumatriptan nasal spray (20 mg/dose) in the acute treatment of cluster headache. Cephalgia 1998, 18:487-489
- Heckl, R. W. 1986. '[Cluster headache and chronic paroxysmal hemicrania--effectiveness of oxygen inhalation]', Nervenarzt, 57: 311-3.
- Jarrar RG and others. Outcome of trigeminal nerve section in the treatment
of chronic cluster headache. Neurology 2003:60:1360-62
- Lambru, G., et al. (2021). "Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis." J Neurol Neurosurg Psychiatry 92(3): 233-241.
- Lipton RB and others. Why headache treatments fail. Neurology 2003:60:1064-1070
- Mathew, N. T., J. Kailasam, and A. Fischer. 2000. 'Responsiveness to celecoxib in chronic paroxysmal hemicrania', Neurology, 55: 316.
- Morelli, N., M. Mancuso, G. Felisati, P. Lozza, A. Maccari, G. Cafforio, S. Gori, L. Murri, and D. Guidetti. 2010. 'Does sphenopalatine endoscopic ganglion block have an effect in paroxysmal hemicrania? A case report', Cephalalgia, 30: 365-7.
- Nesbitt, A. D., et al. (2015). "Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment." Neurology 84(12): 1249-1253.
- Khatimi R, Tararotti S, Siccoli MM, Bassetti CL, Sandor PS. Long term efficacy of sodium oxybate in 4 patients with chronic cluster headache. Neurology 2011:77:67-70
- Markey HL. Topical agents in the treatment of cluster headache. Current pain and headache reports 2003, 7: 139-143
- McGeeney BE. Cluster headache acute therapies. Practical Neurology May 2019, 99-
- Pringsheim, T. (2002). "Cluster headache: evidence for a disorder of circadian
rhythm and hypothalamic function." Can J Neurol Sci 29(1): 33-40.
- Russo et al. (2019)"The "Cluster-SUNCT Syndrome": The Lumper-Splitter Problem." Pain Med 20(2): 421-423.
- Schindler EAD, Gottschalk C. Cluster headache preventive therapies. Practical Neurology May 2019, 93-
- Shabbir, N., and G. McAbee. 1994. 'Adolescent chronic paroxysmal hemicrania responsive to verapamil monotherapy', Headache, 34: 209-10.
- Shakra S, Becker WJ, Werner J, et al. Zolmitriptan nasal spray is effective, fast-acting and well tolerated during both short and long-term treatment. Neurology 2002, 58(suppl 3) A414.
- Warner, J. S., A. W. Wamil, and M. J. McLean. 1994. 'Acetazolamide for the treatment of chronic paroxysmal hemicrania', Headache, 34: 597-9.
- Waung MW and others. Family history of Cluster Headache A systemic review. JAMA neurology. 2020:77(7):887-896