Abnormal tyrosine metabolism in chronic cluster headache

Cephalalgia ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 148-153 ◽  
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.

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

2017 ◽  
Vol 75 (9) ◽  
pp. 620-624 ◽  
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.

Cluster Headache Course Over Ten Years in 189 Patients

Cephalalgia ◽  
1991 ◽  
Vol 11 (4) ◽  
pp. 169-174 ◽  
Author(s):  
Gian Camillo Manzoni ◽  
Giuseppe Micieli ◽  
Franco Granella ◽  
Cristina Tassorelli ◽  
Carla Zanferrari ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Disease Duration ◽  
Chronic Cluster Headache ◽  
Chronic Patients ◽  
Chronic Form ◽  
Prophylactic Drugs ◽  
Long Duration ◽  
Episodic Cluster Headache ◽  
The Moment ◽  
Headache 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.

The M-Chlorophenylpiperazine Test in Cluster Headache

Cephalalgia ◽  
1997 ◽  
Vol 17 (6) ◽  
pp. 666-672 ◽  
Author(s):  
M Leone ◽  
A Attanasio ◽  
D Croci ◽  
G Libro ◽  
L Grazzi ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Plasma Levels ◽  
Baseline Level ◽  
Serum Levels ◽  
Receptor Subtypes ◽  
Hormonal Responses ◽  
Mean Values ◽  
Basal Cortisol ◽  
Episodic Cluster Headache ◽  
Headache Patients

The central serotoninergic agonist m-chlorophenylpiperazine (m-CPP) stimulates several 5HT receptor subtypes. It induces the release of both cortisol and prolactin (PRL). In this study we investigated central serotoninergic responsiveness in cluster headache by monitoring cortisol and PRL responses to m-CPP administration. Twenty-three patients with episodic cluster headache and 17 sex-matched and age-matched healthy subjects were studied. The cluster headache patients were tested during a cluster period, and none were receiving prophylaxis. A single oral dose of m-CPP, 0.5 mg/kg, was given at time 0. Blood samples were drawn at 30, 0, 30, 60, 90, 120, 150 and 180 min. PRL and cortisol levels were assayed in the samples. PRL and cortisol delta maxima: delta maximum = maximum response-baseline level at time 0/baseline level at time 0) were evaluated in each patient and mean values compared. Serum levels of m-CPP were detected by HPLC and correlated to hormonal responses. Reduced cortisol ( p<0.02) and increased PRL ( p<0.05) delta maxima were observed in cluster headache patients. Increased basal cortisol plasma levels ( p<0.05) and reduced basal PRL plasma levels ( p=0.06) also characterized cluster headache patients. This is the first study evaluating central serotoninergic responsiveness to m-CPP in cluster headache and these data suggest impaired central serotoninergic function in this pathology.

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

Cephalalgia ◽  
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).

Ten years of chronic cluster – attacks still cluster

Cephalalgia ◽  
2010 ◽  
Vol 30 (9) ◽  
pp. 1123-1126 ◽  
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.

scholarly journals Calcitonin gene-related peptide and disease activity in cluster headache

Cephalalgia ◽  
2019 ◽  
Vol 39 (5) ◽  
pp. 575-584 ◽  
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.

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

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.

scholarly journals Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts

Cephalalgia ◽  
2020 ◽  
Vol 40 (14) ◽  
pp. 1574-1584 ◽  
Author(s):  
Ruth Ruscheweyh ◽  
Gregor Broessner ◽  
Gudrun Goßrau ◽  
Katja Heinze-Kuhn ◽  
Tim P Jürgens ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Calcitonin Gene Related Peptide ◽  
Chronic Cluster Headache ◽  
Individual Treatment ◽  
Attack Frequency ◽  
Peptide Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Receptor Antibodies ◽  
Headache Patients

Objective To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions. Background Calcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies. Methods Data from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres. Results The number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2–11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by −9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody ( p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (−6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (−9.8 ± 7.6, p < 0.001) and pain intensity during attacks (−1.2 ± 2.0, numerical rating scale (NRS) [0–10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was −8.0 ± 8.4 ( p = 0.004) and −9.1 ± 10.0 ( p = 0.024), respectively. Conclusion Under real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.

Sleep in cluster headache revisited: Results from a controlled actigraphic study

Cephalalgia ◽  
2018 ◽  
Vol 39 (6) ◽  
pp. 742-749 ◽  
Author(s):  
Nunu LT Lund ◽  
Agneta Henriette Snoer ◽  
Poul Jørgen Jennum ◽  
Rigmor Højland Jensen ◽  
Mads Christian J Barloese
Keyword(s):  
Cluster Headache ◽  
Hospital Environment ◽  
Sleep Diaries ◽  
Time In Bed ◽  
Episodic Cluster Headache ◽  
Remission Phase ◽  
Headache Center ◽  
Homeostatic Mechanisms ◽  
Headache Patients

Background and aim Cluster headache attacks exhibit a nocturnal predilection, but little is known of long-term sleep and circadian rhythm. The aim was to compare actigraphy measures, firstly in episodic cluster headache patients in bout and in remission and, secondly, to compare each disease phase with controls. Methods Episodic cluster headache patients (ICHD III-beta), from the Danish Headache Center and healthy, age- and sex-matched controls participated. Sleep and activity were measured using actigraphy continuously for 2 weeks, along with sleep diaries and, for patients, also attack registration. Results Patients in bout (n = 17, 2.3 attacks/day) spent more time in bed (8.4 vs. 7.7 hours, p = 0.021) and slept more (7.2 vs. 6.6 hours, p = 0.036) than controls (n = 15). In remission (n = 11), there were no differences compared with controls. Neither were there differences between patients in the two disease phases. In five patients, attacks/awakenings occurred at the same hour several nights in a row. Conclusion Actigraphy offers the possibility of a continuous and long study period in a natural (non-hospital) environment. The study indicates that sleep does not differ between the bout and remission phase of episodic cluster headache. The repeated attacks/awakenings substantiate that circadian or homeostatic mechanisms are involved in the pathophysiology. The protocol was made available at ClinicalTrials.gov (NCT02853487).

Neuromodulatory Approaches to the Management of Medically Refractory Cluster Headache

2010 ◽  
Vol 5 (1) ◽  
pp. 97
Author(s):  
Arne May ◽  
Peter J Goadsby ◽  
◽  
Keyword(s):  
Cluster Headache ◽  
Treatment Options ◽  
Primary Headache ◽  
Chronic Cluster Headache ◽  
Primary Headache Disorders ◽  
Greater Occipital Nerve ◽  
Term Data ◽  
Deep Brain ◽  
Stimulation Of

The trigeminal autonomic cephalalgias are a group of primary headache disorders characterised by unilateral trigeminal distribution of pain that occurs in association with ipsilateral cranial autonomic features. The most prominent one is cluster headache, a dreadful disease with excrutiating pain attacks. These attacks last no longer than two hours but may occur several times per day. It is mandatory to find an efficient therapy for these patients, but some are unresponsive to all treatments. In these intractable cases invasive procedures are introduced, but the available evidence (while conflicting) illustrates that trigeminal denervation may not be effective in preventing the headache attacks or autonomic symptoms of chronic cluster headache. Modern neurostimulating approaches, such as stimulation of the greater occipital nerve and hypothalamic deep brain stimulation, supersede neurodestructive procedures. Both stimulation methods are exquisite and potentially lifesaving treatment options in otherwise intractable patients, but they need to be better characterised and further long-term data are needed.

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