Cluster Headache Course Over Ten Years in 189 Patients

One-hundred-and-eighty-nine cluster headache patients, referred to Parma and Pavia Headache Centres between 1976 and 1986 with a disease duration of over 10 years, were interviewed about the course of cluster headache. They were classified as episodic (n = 140) or chronic (n = 49) cluster headache patients on the basis of course during the year of onset. Episodic patients showed the following outcome: maintenance of an episodic form (primary episodic form) in 80.7% of cases, shift towards a chronic form (secondary chronic form) in 12.9% and shift towards an intermediate pattern (“combined” form) in 6.4%. In chronic patients, cluster headache was still chronic (primary chronic form) at the moment of observation in 52.4% of cases, while it turned into an episodic form (“secondary” episodic form) in 32.6% and into a “combined” form in 14.3%. Nineteen patients (10%) had had no attacks for at least three years at the moment of examination. We can conclude from our data that: cluster headache is a disease of long duration, perhaps lifelong; episodic cluster headache tends to worsen; chronic cluster headache may easily turn into a better prognostic episodic form; prophylactic drugs are unable to induce recovery. The following factors seem related to a poor outcome: a later onset, the male gender and a disease duration of over 20 years for the episodic forms.

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Clomiphene treatment may be effective in refractory episodic and chronic cluster headache

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20170119 ◽

2017 ◽

Vol 75 (9) ◽

pp. 620-624 ◽

Cited By ~ 6

Author(s):

Maria Eduarda Nobre ◽

Mario Fernando Prieto Peres ◽

Pedro Ferreira Moreira Filho ◽

Antonio José Leal

Keyword(s):

Complete Remission ◽

Cluster Headache ◽

Chronic Cluster Headache ◽

Free Time ◽

Chronic Patients ◽

Conventional Medication ◽

Episodic Cluster Headache ◽

Cluster Headaches ◽

Headache Patients

ABSTRACT Objective To describe the evolution of 15 patients who were treated for difficult-to-control episodic and chronic cluster headaches with clomiphene. Methods Clomiphene treatment was used for seven chronic and eight episodic cluster headache patients. The chronic patients were refractory to the medication being used, and the episodic patients, in addition to being resistant to conventional medication, had longer cluster headache periods, exceeding the average time of previous cluster cycles. Our main analysis was of the time to pain-free, complete remission, and the length of pain-free time and complete remission. Results Clomiphene was used for 45-180 days. The average time to being pain-free was 15 days and cluster remission was up to 60 days. The average time between being pain-free until cluster remission was 26 days. Conclusions Clomiphene treatment was significantly efficient. It interrupted chronicity in all patients, suggesting the capability of changing the pattern of attacks. It proved to be safe and well tolerated.

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Abnormal tyrosine metabolism in chronic cluster headache

Cephalalgia ◽

10.1177/0333102416640502 ◽

2016 ◽

Vol 37 (2) ◽

pp. 148-153 ◽

Cited By ~ 14

Author(s):

Giovanni D’Andrea ◽

Massimo Leone ◽

Gennaro Bussone ◽

Paola Di Fiore ◽

Andrea Bolner ◽

...

Keyword(s):

Cluster Headache ◽

Plasma Levels ◽

Primary Headache ◽

Chronic Cluster Headache ◽

Predisposing Factor ◽

Episodic Cluster Headache ◽

Tyrosine Metabolism ◽

Low Levels ◽

And Control ◽

Headache Patients

Objective Episodic cluster headache is characterized by abnormalities in tyrosine metabolism (i.e. elevated levels of dopamine, tyramine, octopamine and synephrine and low levels of noradrenalin in plasma and platelets.) It is unknown, however, if such biochemical anomalies are present and/or constitute a predisposing factor in chronic cluster headache. To test this hypothesis, we measured the levels of dopamine and noradrenaline together with those of elusive amines, such as tyramine, octopamine and synephrine, in plasma of chronic cluster patients and control individuals. Methods Plasma levels of dopamine, noradrenaline and trace amines, including tyramine, octopamine and synephrine, were measured in a group of 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster), and 16 control participants. Results The plasma levels of dopamine, noradrenaline and tyramine were several times higher in chronic cluster headache patients compared with controls. The levels of octopamine and synephrine were significantly lower in plasma of these patients with respect to control individuals. Conclusions These results suggest that anomalies in tyrosine metabolism play a role in the pathogenesis of chronic cluster headache and constitute a predisposing factor for the transformation of the episodic into a chronic form of this primary headache.

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Changes in medication cost observed in chronic cluster headache patients treated with sphenopalatine ganglion (SPG) stimulation: Analysis based on 1-year data from the Pathway R-1 Registry

Cephalalgia ◽

10.1177/0333102418784689 ◽

2018 ◽

Vol 38 (8) ◽

pp. 1455-1462 ◽

Cited By ~ 8

Author(s):

Jan B Pietzsch ◽

Simon A Weber ◽

Nunu Lund ◽

Charly Gaul

Keyword(s):

Cluster Headache ◽

Cost Savings ◽

Chronic Cluster Headache ◽

Medication Cost ◽

Base Case ◽

Sphenopalatine Ganglion ◽

Chronic Patients ◽

Medication Costs ◽

Preventive Medication ◽

Headache Patients

Background On-demand stimulation of the sphenopalatine ganglion (SPG) by means of an implantable neurostimulation system has been shown to be a safe and effective therapy for treatment-refractory cluster headache patients. Our objective was to estimate changes in cluster headache medication cost observed in SPG-treated chronic patients. Methods Detailed patient-level data of 71 chronic patients treated with the Pulsante® SPG Microstimulator System were available from the Pathway R-1 Registry through 12 months’ follow-up. We used utilization data of preventive and acute medications reported at baseline, 3, 6, 9, and 12 months to estimate annualized drug costs for SPG-treated patients and compared it to baseline. Cost estimates for all drug/dosage combinations were developed based on German medication prices for 2016. Results In the base case analysis, mean annual acute and preventive medication costs decreased from €14,178 to €6924 (−€7254; −51%), and €559 to €328 (−€231; −41%), respectively, leading to total estimated annual drug cost savings of €7484, 97% of which were attributable to acute medications. Conclusions Our analysis suggests that SPG stimulation for the treatment of chronic cluster headache is associated with pronounced reductions in cluster headache medication usage that might lead to sizable annual savings in medication costs.

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Episodic Cluster Headache in a Community: Clinical Features and Treatment

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100033758 ◽

1998 ◽

Vol 25 (2) ◽

pp. 141-145 ◽

Cited By ~ 14

Author(s):

C.M. Riess ◽

W.J. Becker ◽

M. Robertson

Keyword(s):

Cluster Headache ◽

Clinical Features ◽

International Headache Society ◽

Media Campaign ◽

Dental Procedures ◽

Prophylactic Drugs ◽

Episodic Cluster Headache ◽

Ihs Criteria ◽

The Media ◽

Headache Patients

ABSTRACT:Objective:To study the clinical features and treatment given to episodic cluster headache patients in the Calgary region.Patients:Fifty-one (51) patients who responded to a media campaign, had previously been diagnosed by their family physicians, and who met International Headache Society (IHS) criteria for episodic cluster headache, formed the population for this study.Methods:The media campaign consisted of newspaper advertisements and radio publicity including physician interviews and talk shows. Patients were required to complete a 200-item questionnaire detailing clinical features and treatment of their cluster headache syndrome. Each patient was also interviewed by our research nurse for clarification and proper completion of questionnaire.Results:Fifty-one percent (51%) of our patients had short headache attacks lasting one hour or less. Almost one-half (45%) had three or four attacks per 24 hour period. Eighty-six percent (86%) had been referred to a neurologist. Sixty-nine percent (69%) had never used oxygen, but of those who had, onehalf were still using it. Sumatriptan by injection had been tried by 26% of patients and of these, 93% considered it effective. Subcutaneous dihydroergotamine had been tried by 8%. For prophylaxis, 41% had tried methysergide, 31% prednisone, and 4% verapamil. Many patients had been prescribed migraine prophylactic drugs which are ineffective for cluster headache, and some had also undergone dental procedures or nasal and sinus surgeries.Conclusion:Many cluster headache patients had not, to their knowledge, been prescribed or used the best symptomatic and prophylactic treatments for cluster headache. This should be addressed through educational programs and through making up-to-date information on the treatment of cluster headache readily available to physicians and patients.

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Great occipital nerve long-acting steroid injections in cluster headache therapy: an observational prospective study

Journal of Neurology ◽

10.1007/s00415-021-10884-0 ◽

2021 ◽

Author(s):

Elena Merli ◽

Gian Maria Asioli ◽

Valentina Favoni ◽

Corrado Zenesini ◽

Davide Mascarella ◽

...

Keyword(s):

Adverse Events ◽

Cluster Headache ◽

Chronic Cluster Headache ◽

Chronic Patients ◽

Steroid Injections ◽

Occipital Nerve ◽

First Choice ◽

Greater Occipital Nerve ◽

Long Acting ◽

Headache Patients

Abstract Background Injections targeting the occipital nerve are used to reduce headache attacks and abort cluster bouts in cluster headache patients. There is no widely accepted agreement over the optimal technique of injection, type and doses of steroids and/or anesthetics to use, as well as injection regimens. The aim of this study was to verify the effectiveness and safety of greater occipital nerve long-acting steroid injections in the management of episodic and chronic cluster headache. Methods We conducted a prospective observational cohort study on episodic (ECH) and chronic cluster headache patients (CCH). ECH were included in the study at the beginning of a cluster period. Three injections with 60 mg methylprednisolone were performed on alternate days. We registered the frequency and intensity of attacks three days before and 3, 7 and 30 days after the treatment, the latency of cluster relapse, adverse events, scores evaluating anxiety (Zung scale), depression (Beck’s Depression Scale) and quality of life (Disability Assessment Schedule II, 12-Item Self-Administered Version). Primary outcome was the interruption of the cluster after the three injections. Responders conducted a follow-up period of 12 months. Results We enrolled 60 patients, 47 with ECH and 13 with CCH. We observed a complete response in 47.8% (22/46) of episodic and 33.3% (4/12) of chronic patients. Moreover, a partial response (reduction of at least 50% of attacks) was obtained in further 10.8% (5/46) of episodic and in 33.3% (4/12) of chronic patients at 1 month. Median pain-free period was of 3 months for CCH responders. Only mild adverse events were reported in 38.3% (23/58) cases. Conclusions We suggest three greater occipital nerve injections of 60 mg methylprednisolone on alternate days as useful therapy in episodic and chronic cluster headache. This leads to a long pain-free period in chronic forms. Adverse effects are mild and support its use as first choice. Trial registration The study was inserted in AIFA observational studies register.

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Pre-attack signs and symptoms in cluster headache: Characteristics and time profile

Cephalalgia ◽

10.1177/0333102417726498 ◽

2017 ◽

Vol 38 (6) ◽

pp. 1128-1137 ◽

Cited By ~ 15

Author(s):

Agneta Snoer ◽

Nunu Lund ◽

Rasmus Beske ◽

Rigmor Jensen ◽

Mads Barloese

Keyword(s):

Cluster Headache ◽

Signs And Symptoms ◽

Structured Interview ◽

Chronic Cluster Headache ◽

Time Profile ◽

Chronic Patients ◽

Prodromal Phase ◽

Cluster Headache Attack ◽

Episodic Cluster Headache ◽

Accompanying Symptoms

Introduction In contrast to the premonitory phase of migraine, little is known about the pre-attack (prodromal) phase of a cluster headache. We aimed to describe the nature, prevalence, and duration of pre-attack symptoms in cluster headache. Methods Eighty patients with episodic cluster headache or chronic cluster headache, according to ICHD-3 beta criteria, were invited to participate. In this observational study, patients underwent a semi-structured interview where they were asked about the presence of 31 symptoms/signs in relation to a typical cluster headache attack. Symptoms included previously reported cluster headache pre-attack symptoms, premonitory migraine symptoms and accompanying symptoms of migraine and cluster headache. Results Pre-attack symptoms were reported by 83.3% of patients, with an average of 4.25 (SD 3.9) per patient. Local and painful symptoms, occurring with a median of 10 minutes before attack, were reported by 70%. Local and painless symptoms and signs, occurring with a median of 10 minutes before attack, were reported by 43.8% and general symptoms, occurring with a median of 20 minutes before attack, were reported by 62.5% of patients. Apart from a dull/aching sensation in the attack area being significantly ( p < 0.05) more frequent among men and episodic patients, compared with women and chronic patients respectively, no other differences in the prevalence of pre-attack symptoms were identified between groups. Conclusion Pre-attack symptoms are frequent in cluster headache. Since the origin of cluster headache attacks is still unresolved, studies of pre-attack symptoms could contribute to the understanding of cluster headache pathophysiology. Furthermore, identification and recognition of pre-attack symptoms could potentially allow earlier abortive treatment.

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The effect of pituitary adenylate cyclase-activating peptide-38 and vasoactive intestinal peptide in cluster headache

Cephalalgia ◽

10.1177/0333102420940689 ◽

2020 ◽

Vol 40 (13) ◽

pp. 1474-1488

Author(s):

Anne Luise H Vollesen ◽

Agneta Snoer ◽

Basit Chaudhry ◽

Anja Sofie Petersen ◽

Andreas Hagedorn ◽

...

Keyword(s):

Adenylate Cyclase ◽

Cluster Headache ◽

Vasoactive Intestinal Peptide ◽

Active Phase ◽

Chronic Cluster Headache ◽

Cluster Headache Attack ◽

Episodic Cluster Headache ◽

Pituitary Adenylate Cyclase ◽

Remission Phase ◽

Headache Patients

Background Previously reported increases in serum levels of vasodilating neuropeptides pituitary adenylate cyclase-activating peptide-38 (PACAP38) and vasoactive intestinal peptide (VIP) during attacks of cluster headache could indicate their involvement in cluster headache attack initiation. We investigated the attack-inducing effects of PACAP38 and vasoactive intestinal peptide in cluster headache, hypothesising that PACAP38, but not vasoactive intestinal peptide, would induce cluster-like attacks in episodic active phase and chronic cluster headache patients. Methods In a double-blind crossover study, 14 episodic cluster headache patients in active phase, 15 episodic cluster headache patients in remission phase and 15 chronic cluster headache patients were randomly allocated to receive intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal peptide (8 pmol/kg/min) over 20 min on two study days separated by at least 7 days. We recorded headache intensity, incidence of cluster-like attacks, cranial autonomic symptoms and vital signs using a questionnaire (0–90 min). Results In episodic cluster headache active phase, PACAP38 induced cluster-like attacks in 6/14 patients and vasoactive intestinal peptide induced cluster-like attacks in 5/14 patients ( p = 1.000). In chronic cluster headache, PACAP38 and vasoactive intestinal peptide both induced cluster-like attacks in 7/15 patients ( p = 0.765). In episodic cluster headache remission phase, neither PACAP38 nor vasoactive intestinal peptide induced cluster-like attacks. Conclusions Contrary to our hypothesis, attack induction was lower than expected and roughly equal by PACAP38 and vasoactive intestinal peptide in episodic active phase and chronic cluster headache patients, which contradicts the PAC1-receptor as being solely responsible for attack induction. Trial registration: clinicaltrials.gov (identifier NCT03814226).

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Ten years of chronic cluster – attacks still cluster

Cephalalgia ◽

10.1177/0333102409351754 ◽

2010 ◽

Vol 30 (9) ◽

pp. 1123-1126 ◽

Cited By ~ 10

Author(s):

Tim P Jürgens ◽

Horst J Koch ◽

Arne May

Keyword(s):

Spectral Analysis ◽

Cluster Headache ◽

Chronic Cluster Headache ◽

Circannual Rhythm ◽

Cosinor Analysis ◽

Curve Fit ◽

Episodic Cluster Headache ◽

Headache Patients ◽

Observation Period ◽

Cosinor Models

The chronic variant can be found in 10–20% of all cluster headache patients. While circadian and circannual rhythmicity are characteristic of the episodic variant, little is known on chronobiology in chronic cluster headache. We report a patient with chronic cluster evolved from episodic who recorded a total of 5447 attacks over 10 years. After spectral analysis, cosinor models were calculated within the frequency ranges of 23–25 h (circadian) and 11–13 months (circannual), respectively. Significant results ( P < 0.01) were found for 24-h periods, but not for circannual intervals (12 months). However, with regard to circannual periodicity, a semi-circannual rhythm (5–7 months) was suitable for curve fit and yielded significant results in the cosinor analysis at 6 months ( P < 0.05). This remarkable long observation period of 10 years shows that, at least for secondary chronic cluster headache which evolved from the episodic form, a typical circadian and circannual rhythmicity comparable to that of episodic cluster headache exists.

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Calcitonin gene-related peptide and disease activity in cluster headache

Cephalalgia ◽

10.1177/0333102419837154 ◽

2019 ◽

Vol 39 (5) ◽

pp. 575-584 ◽

Cited By ~ 15

Author(s):

Agneta Snoer ◽

Anne Luise H Vollesen ◽

Rasmus P Beske ◽

Song Guo ◽

Jan Hoffmann ◽

...

Keyword(s):

Cluster Headache ◽

Vasoactive Intestinal Polypeptide ◽

Active Phase ◽

Calcitonin Gene Related Peptide ◽

Chronic Cluster Headache ◽

Related Peptide ◽

Episodic Cluster Headache ◽

Calcitonin Gene ◽

Headache Patients ◽

Intestinal Polypeptide

Objective To investigate the role of calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide in cluster headache, we measured these vasoactive peptides interictally and during experimentally induced cluster headache attacks. Methods We included patients with episodic cluster headache in an active phase (n = 9), episodic cluster headache patients in remission (n = 9) and patients with chronic cluster headache (n = 13). Cluster headache attacks were induced by infusion of calcitonin gene-related peptide (1.5 µg/min) in a randomized, double-blind, placebo controlled, two-way cross-over study. At baseline, we collected interictal blood samples from all patients and during 11 calcitonin gene-related peptide-induced cluster headache attacks. Results At baseline, episodic cluster headache patients in remission had higher plasma levels of calcitonin gene-related peptide, 100.6 ± 36.3 pmol/l, compared to chronic cluster headache patients, 65.9 ± 30.5 pmol/l, ( p = 0.011). Episodic cluster headache patients in active phase had higher PACAP38 levels, 4.0 ± 0.8 pmol/l, compared to chronic cluster headache patients, 3.3 ± 0.7 pmol/l, ( p = 0.033). Baseline levels of vasoactive intestinal polypeptide did not differ between cluster headache groups. We found no attack-related increase in calcitonin gene-related peptide, PACAP38 or vasoactive intestinal polypeptide levels during calcitonin gene-related peptide-induced cluster headache attacks. Conclusions This study suggests that cluster headache disease activity is associated with alterations of calcitonin gene-related peptide expression. Future studies should investigate the potential of using calcitonin gene-related peptide measurements in monitoring of disease state and predicting response to preventive treatments, including response to anti-calcitonin gene-related peptide monoclonal antibodies.

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Efficacy of transdermal rotigotine in chronic cluster headache: A case series

Cephalalgia Reports ◽

10.1177/2515816318809697 ◽

2018 ◽

Vol 1 ◽

pp. 251581631880969

Author(s):

Cherubino Di Lorenzo ◽

Lanfranco Pellesi ◽

Gianluca Coppola ◽

Vincenzo Parisi ◽

Maurizio Evangelista ◽

...

Keyword(s):

Cluster Headache ◽

Case Series ◽

Chronic Cluster Headache ◽

Drug Resistant ◽

Transdermal Patch ◽

Full Resolution ◽

Episodic Cluster Headache ◽

Monoaminergic System ◽

Rotigotine Transdermal Patch ◽

Effective Treatments

Cluster headache (CH) is one of the most severe forms of headache, but the number of effective treatments is still limited. Recently, we reported the case of a drug-resistant CH patient responsive to the rotigotine transdermal patch, which is used in the treatment of Parkinson’s disease. This report formed the basis for a case series where other drug-resistant CH patients were treated with rotigotine. Here are the results of this study. Twenty-two CH patients underwent the treatment. Eight were episodic cluster headache (ECH) patients and 14 were chronic cluster headache (CCH) patients. Of the eight ECH patients, four reported that their CH had been stopped by the treatment. Of the 14 CCH patients, 11 were considered responders to the treatment (5 experienced a full resolution of headache, and 6 had a headache reduction of at least 50% in terms of mean monthly number of attacks). Our case series confirms the previous observation that rotigotine could be helpful in the treatment of CH. It may even influence the monoaminergic system that has a key role in the pathogenesis of CH.

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