Cluster Headache Highlights at AHS 2019


The latest advances in diagnosis and treatment are discussed in meeting presentations and recent studies and reviews.

Headache skeleton brain

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Advances in cluster headache treatment are highlighted at the American Headache Society 61st Annual Scientific Meeting in Philadelphia. The meeting takes place from July 11 to 14, 2019.

Recent FDA approvals

The FDA approved galcanezumab-gnlm (Emgality®) for the treatment of episodic cluster headache in adults on June 4, 2019. A self-injection treatment, galcanezumab was approved by the FDA for the preventive treatment of migraine in adults in September 2018.

Key studies and reviews

Study patients who had cluster headache with comorbid migraine had a shorter duration of cluster headache after the first episode, a lower frequency of episodic cluster headache, and a higher frequency of chronic cluster headache. Psychiatric comorbidities did not differ between patients who did or did not have comorbid migraine. The headaches could be distinguished based on their trigeminal autonomic symptoms, pulsating character, severity, and pain location. The authors concluded that the distinct characteristics of cluster headache remain unchanged in patients with comorbid migraine, except for an increased frequency of chronic cluster headache and suggested that clinicians check the history of preceding migraine, particularly in cases of chronic cluster headache.

• The authors of a review of management options for cluster headache noted that most patients with cluster headache have a delayed diagnosis and will have seen three general practitioners before being referred to neurology services. They suggested that early diagnosis allows for appropriate treatment, acute management should involve sumatriptan subcutaneous injections and oxygen, patients with atypical cluster headaches and those who do not respond to treatment should undergo MRI scanning of the brain with gadolinium and pituitary function testing, and patients with episodic cluster headache should be weaned off prophylaxis after the bout ends.

• In two randomized, double-blind, sham-controlled trials that evaluated noninvasive vagus nerve stimulation (nVNS) as acute treatment for cluster headache, nVNS was superior to sham in episodic but not chronic cluster headache. The authors concluded that nVNS is a well-tolerated and effective acute treatment for episodic cluster headache.

• In a recent study, burst occipital nerve stimulation produced a statistically significant mean reduction of 10.2 headache days per month in patients with chronic migraine. There were significant mean reductions in headache frequency (92%) and intensity (42%) in patients with chronic cluster headache.

Review authors hypothesized that changes in the brain’s state associated with light, sleep, and the biological clock can lower the threshold for activating the trigeminal-autonomic reflex and result in a cluster headache attack. They suggested that understanding the mechanisms that contribute to the daily and seasonal fluctuations in cluster headache attacks may provide new therapeutic targets.

Researchers measured plasma levels of 4 neurosteroids-allopregnanolone, epiallopregnanolone, dehydroepiandrosterone and deydroepiandrosterone sulfate-in patients affected by episodic migraine, chronic migraine, or cluster headache. Their findings showed that that large and disease-specific changes in circulating neurosteroid levels are associated with chronic headache disorders and that fluctuations of neurosteroids at their site of action might shape the natural course of migraine and cluster headache.

• In a comparison of cluster headache attack descriptions, investigators found important differences between prospectively and retrospectively reported attacks. Retrospective attack descriptions were significantly longer and more severe for untreated attacks than prospective reports. The number of autonomic symptoms was significantly higher in the retrospective reports than in the prospective reports. Within‐patient variability for attack duration, pain severity, and number of autonomic and migrainous symptoms was low. Women reported longer and more severe attacks with more migrainous symptoms. The researchers suggested that the high prevalence of symptoms typically associated with migraine should raise more diagnostic awareness for cluster headache, especially in women.


1. Global Leaders in Migraine Research to Convene at The American Headache Society 61st Annual Scientific Meeting [press release]. Mount Royal, NJ: American Headache Society. July 8, 2019. Accessed July 9, 2019.

2. Recent Developments in Migraine and Cluster Headache Treatment [press release]. Mount Royal, NJ: American Headache Society. June 6, 2019. Accessed July 10, 2019.

3. Song TJ, Lee MJ, Choi Y, et al. Differences in characteristics and comorbidity of cluster headache according to the presence of migraine. J Clin Neurol. 2019;15:334-338. doi: 10.3988/jcn.2019.15.3.334.

4. Wei DY, Khalil M, Goadsby PJ. Managing cluster headache. Pract Neurol. 2019 Jul 5. pii: practneurol-2018-002124. doi: 10.1136/practneurol-2018-002124. [Epub ahead of print]

5. de Coo IF, Marin JC, Silberstein SD, et al. Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: a meta-analysis. Cephalalgia. 2019;39:967-977. doi: 10.1177/0333102419856607. Epub 2019 Jun 10.

6. Garcia-Ortega R, Edwards T1Moir L, et al. Burst occipital nerve stimulation for chronic migraine and chronic cluster headache. Neuromodulation. 2019 Jun 14. doi: 10.1111/ner.12977. [Epub ahead of print]

7. Naber WC, Fronczek R, Haan J, et al. The biological clock in cluster headache: a review and hypothesis. Cephalalgia. 2019;29:333102419851815. doi: 10.1177/0333102419851815. [Epub ahead of print]

8. Koverech A, Cicione C, Lionetto L, et al. Migraine and cluster headache show impaired neurosteroids patterns. J Headache Pain. 2019 May 27;20(1):61. doi: 10.1186/s10194-019-1005-0.

9. Snoer AH, Lund N, Jensen RH, et al. More precise phenotyping of cluster headache using prospective attack reports. Eur J Neurol. 2019 May 6. doi: 10.1111/ene.13980. [Epub ahead of print]

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