Episodic Cluster Headache Research Articles

Transcranial Magnetic Stimulation Reveals Cortical Hyperexcitability in Episodic Cluster Headache

Evidence shows involvement of the cerebral cortex in the pathophysiology of cluster headache (CH). Here we investigated cortical excitability in episodic CH patients by using transcranial magnetic stimulation. In 25 patients with episodic CH and 13 healthy subjects we evaluated the motor cortical response to single-pulse (ie, motor threshold, input-output curves, cortical silent period) and paired-pulse (ie, intracortical facilitation, short intracortical inhibition) transcranial magnetic stimulation in both hemispheres. Thirteen patients were evaluated outside bout and the remaining 12 patients inside bout. Our results showed increased slope of the input-output curves after stimulation of both hemispheres in patients outside bout and in the hemisphere contralateral to the headache side in patients inside bout. Increased intracortical facilitation was observed in the hemisphere ipsilateral to the headache side in patients evaluated both outside and inside bout; reduced short intracortical inhibition was observed in patients inside bout ipsilateral to the side of pain. In conclusion, we provide evidence of increased cortical excitability in episodic CH both outside and inside bout, especially in the hemisphere ipsilateral to the side of headache attacks. Our results suggest that an abnormal regulation of cortical excitability could be involved in the pathophysiology of CH. PerspectivesWe investigated cortical excitability in episodic cluster headache by using transcranial magnetic stimulation, providing evidence of cortical hyperexcitability in patients both inside and outside bout. We suggest that an abnormal state of cortical excitability could be involved in the pathophysiology of the disease.

Study of cluster headache: A hospital-based study.

Introduction:Cluster headache (CH) is uncommon and most painful of all primary headaches, and continues to be managed suboptimally because of wrong diagnosis. It needs to be diagnosed correctly and specifically treated. There are few studies and none from this region on CH.Materials and Methods:To study the detailed clinical profile of CH patients and to compare them among both the genders. Study was conducted at Mahatma Gandhi hospital, Jodhpur (from January 2011to December 2013). Study comprises 30 CH patients diagnosed according to International Headache Society guidelines (ICHD-II). Routine investigations and MRI brain was done in all patients. All measurements were reported as mean ± SD. Categorical variables were compared using the Chi-square test, and continuous variables were compared using Student's t-test. SPSS for Windows, Version 16.0, was used for statistical analyses with the significance level set at P = 0.05.Results:M: F ratio was 9:1. Age at presentation was from 22-60 years (mean - 38 years). Latency before diagnosis was 3 months-12 years (mean - 3.5 years). All suffered from episodic CH and aura was found in none. Pain was strictly unilateral (right-19, left-11), predominantly over temporal region-18 (60%). Pain intensity was severe in 27 (90%) and moderate in 3 (10%). Pain quality was throbbing in 12 (40%). Peak intensity was reached in 5 minutes-30 minutes and attack duration varied from 30 minutes to 3 hours (mean - 2.45 hours). Among autonomic features, conjunctival injection-23 (76.6%) and lacrimation-25 (83.3%) were most common. Restlessness during episode was found in 80%. CH duration varied from 10 days to 12 weeks. Circadian periodicity for attacks was noted in 24 (80%).Conclusion:Results are consistent with other studies on many accounts, but is different from Western studies with respect to low frequency of family history, chronic CH, restlessness and aura preceeding the attack. Detailed elicitation of history is paramount as misdiagnosis is common.

EHMTI-0149. Low CSF hypocretin-1 levels are associated with cluster headache

Results We found lower HCRT-1 levels in both chronic (388.67 pg/ml, p = 0.0221) and episodic cluster headache (375.36 pg/ml, p = 0.0005) compared with controls (430.96 pg/ml) and a tendency towards relatively higher values in chronic CH compared with episodic CH. A positive relationship between the CH index and HCRT concentrations was found in all patients (R2 = 0.1541, p = 0.0473). We also identified a tendency towards relatively higher HCRT concentrations in patients without chronological rhythmicity.

EHMTI-0069. The low prevalence of “forehead and facial flushing” and “sensation of fullness in the ear” in Japanese cluster headache patients

Results All patients were episodic cluster headache. Two patients (9%) had “forehead and facial flushing” and 4 patients (17%) had “sensation of fullness in the ear”. The patients with “forehead and facial flushing” had also “sensation of fullness in the ear”. The prevalence of “forehead and facial flushing” and “sensation of fullness in the ear” in our study were lower than that of previous Caucasian study (20.0% reported “forehead and facial flushing” and 33.3% “sensation of fullness in the ear”). Conclusion The low prevalence of “forehead and facial flushing” and “sensation of fullness in the ear” may be clinical characteristic in Japanese cluster headache patients. No conflict of interest.

Lateralized nociceptive blink reflex habituation deficit in episodic cluster headache: Correlations with clinical features.

We previously observed impaired habituation mechanisms of the conventional blink reflex (BR) in patients with episodic cluster headache (ECH) during the bout, studying only the affected side. Here, we have studied the nociceptive-specific BR (nBR) both on the affected and non-affected sides, and in relation to clinical features. We recorded nBR in 18 ECH patients during the bout, and in 18 healthy volunteers (HVs). We compared pain threshold, area, and habituation of the nBR, recorded both for the affected and non-affected sides. In patients, the pain threshold on the affected side was lower than that of the non-affected side (p = 0.009), and lower than in HVs (p = 0.038). Reflex area was decreased on both sides (p < 0.05) compared with HVs, whereas habituation was significantly impaired only on the affected side (p = 0.025 vs. HVs; p = 0.003 vs. non-affected). The habituation slope was positively correlated with the number of days since the onset of the bout and the daily attack frequency. Our data reflect lateralized pathological variations in craniofacial nociception in ECH patients over the course of the cluster period. We hypothesized that this is due to malfunctioning of mechanisms that regulate hypothalamic activity and descending aminergic controls.

Reduced cranial parasympathetic tone during the remission phase of cluster headache.

Cluster headache (CH) attacks are accompanied by cranial autonomic symptoms indicative of parasympathetic hyperactivity and sympathetic dysfunction ipsilateral to the pain. We aimed to assess cranial autonomic function in CH patients during the remission phase of cluster headache. During a remission phase, 38 episodic CH patients underwent the following: dynamic pupillometry, measurement of the superficial temporal artery diameter by ultrasound, and measurement of the retinal vessel diameters from digital retinal photographs. Pupillometry was also performed on 30 age- and sex-matched healthy controls. Thirty patients were included (27 men, three women, mean age 50.2 years ± 12.6). Seven patients reported occasional side shift of their headache, but with a clear predominating side. Significantly reduced average pupillary constriction velocity and retinal venular diameter on the CH pain side were found. There was no asymmetry of the superficial temporal artery diameters. Compared to healthy controls, cluster patients displayed bilaterally reduced pupillary average and maximum constriction velocities, reduced constriction in percentage and increased latency of the light reflex. The present findings indicate a bilaterally reduced cranial parasympathetic tone in CH patients in remission phase, with significant lateralization to the CH pain side. This implies a central origin, and a central pathophysiological model of CH is discussed.

Sleep apnea in patients with cluster headache: a case-control study.

Polysomnographic investigations have shown an unspecific association between cluster headache and obstructive sleep apnea syndrome. The aim of this study was to investigate this association in a cluster episode compared with a symptom free interval, and to further characterize this association. We investigated 42 patients with episodic (n = 26) or chronic (n = 16) cluster headache by means of polygraphic screening for sleep apnea and compared the data to 28 healthy control subjects matched according to age, sex, and BMI. The patients with episodic cluster headache were screened twice, once in a cluster episode and once in a symptom free interval. Patients with active cluster headache showed a significantly higher respiratory distress index (8.6 ± 16.0) compared with healthy control subjects (3.4 ± 2.1; p = 0.002). More patients fulfilled the criteria for an obstructive sleep apnea syndrome (29%) than control subjects (7%; p = 0.018). Patients only, but not the control subjects, had central apneas. These differences were only significant when measured during an active cluster episode but not during a symptom free interval. Cluster headache is associated with a sleep apnea syndrome only in the active cluster episode. The increased rate of central apneas might be a result of involvement of the hypothalamus in the pathophysiology of cluster headache. Out of five anecdotal cases treated with nasal continuous positive airway pressure, only one patient showed benefit with respect to cluster headache attack frequency.

Sleep in trigeminal autonomic cephalagias: a review.

Sleep and cluster headache (CH) are believed to be interconnected but the precise relation to the other trigeminal autonomic cephalalgias (TACs) is uncertain and complex. A better understanding of these relations may eventually lead to a clarification of the underlying mechanisms and eventually to more effective therapeutic regimens. This review aims to evaluate the existing literature on the subject of TACs and sleep. An association between episodic CH and distinct macrostructural sleep phases, especially the relation to rapid eye movement (REM) sleep, has been described in some older studies but could not be confirmed in other, more recent studies. Investigations into the microstructure of sleep in these patients are lacking. Only a few case reports exist on the relation between sleep and other TACs. Recent studies do not find an association between CH and REM sleep. One older study suggests chronic paroxysmal hemicranias may be locked to REM sleep but otherwise the relation is unknown. Reports indicate that CH and obstructive sleep apnoea are associated in some individuals but results are diverging. Single cases show improvement of CH upon treatment of sleep apnoea, but the causal relationship remains in question. Other TACs are probably not connected to sleep and strictly nocturnal attacks should prompt investigations for secondary causes. The relation between CH and sleep is, however, fascinating and detailed sleep studies in carefully diagnosed patients are warranted.

Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study

BackgroundNeuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (CH). Disruptions in non-traditional pain processing areas, including the cerebellum and visual cortex, have also been reported in CH....

Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker of cranial parasympathetic activation in chronic migraine.

The aim of this article is to determine vasoactive intestinal peptide (VIP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM). Women older than 17 and diagnosed as CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. VIP levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack, the patients having taken no symptomatic medication the day before. For ethical reasons, preventives were not stopped. We assessed plasma samples from 119 women with CM, 33 healthy women, 51 matched women with EM and 18 patients (16 males) with cluster headache matched for age. VIP levels were significantly increased in CM (165.1 pg/ml) as compared to control healthy women (88.5 pg/ml) and episodic cluster headache patients (101.1 pg/ml). VIP levels in EM (134.9 pg/ml) were significantly higher compared to controls and numerically lower than those of CM. Thresholds of 71.8 and 164.5 pg/ml optimized the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. Variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventive treatment did not significantly influence VIP levels. Increased interictal VIP level measured in peripheral blood could be a biomarker helping in CM diagnosis, though it does not clearly differentiate between EM and CM.

Altered white matter microstructural connectivity in cluster headaches: A longitudinal diffusion tensor imaging study

Functional and structural disruptions to the pain matrix, which may involve changes in white matter (WM) pathways connecting the pain-processing system and hypothalamus, have been implicated in the pathophysiology of cluster headache (CH). However, previous studies have obtained inconclusive results regarding WM changes in CH, and WM variations between "in-bout" and "out-of-bout" periods of CH remain to be determined. Multiple diffusivity indices obtained by diffusion tensor imaging (DTI) and post-hoc probabilistic tractography were used to elucidate CH pathophysiology. Compared to healthy participants, in-bout CH patients showed regionally higher absolute (radial and mean) diffusivities in the left medial frontal gyrus and frontal sub-gyrus and lower absolute (axial, radial and mean) diffusivities in the right parahippocampal gyrus of the limbic lobe. These changes during the in-bout period generally persisted in the out-of-bout period, except for the left cerebellar tonsil. Post-hoc probabilistic tractography showed highly consistent anatomical connections between these altered areas and the hypothalamus across participants. Distinct WM changes were observed in episodic CH. Connections between the pain-modulation areas and hypothalamus may be involved in CH pathophysiology.

Nociception specific supraorbital nerve stimulation may prevent cluster headache attacks: Serendipity in a blink reflex study

In cluster headache, neuromodulation is offered when patients are refractory to pharmacological prophylaxis. Non-invasive peripheral neuromodulatory approaches are of interest. We will focus on these and particularly on nociception specific, transcutaneous supraorbital nerve stimulation. In a study using the nociception specific blink reflex, we made a serendipitous discovery, notably the potential prophylactic effect of bilateral, time contingent, nociception specific, transcutaneous stimulation of the supraorbital nerve. We report on a case series of seven cluster headache patients, in whom attacks seemed to disappear during repeated stimulation of the supraorbital nerves. Three patients stopped experiencing attacks since study participation. Bilateral, time contingent, nociception specific, transcutaneous supraorbital nerve stimulation may have a prophylactic effect in episodic and chronic cluster headache. Given its limited side effects and its non-invasive nature, further studies to investigate this potential peripheral neuromodulatory approach for both episodic and chronic cluster headache are warranted.

Temperature variation and the incidence of cluster headache periods: A nationwide population study

Cluster headache (CH) is well known to show a seasonal predilection; however, the impact of temperature and other meteorological factors on cluster periods (or bouts) has not been established. This nationwide survey included 758 patients with episodic CH retrieved from the Taiwan National Health Insurance Research Database from 2005 to 2009. Corresponding meteorological recordings were obtained from the Central Weather Bureau. A case-crossover study design was used to investigate the association between cluster periods and meteorological factors. A total of 2452 episodes of cluster periods were recorded. The cluster periods were most frequent in the autumn and least frequent in the winter. Seasonal changes from winter to spring and from autumn to winter also increased the frequency of cluster periods. The risk of cluster periods increased when there was a higher mean temperature on event days (odds ratio (OR), 1.014, 95% confidence interval (CI), 1.005-1.023, p = 0.003) or within seven to 56 days. Either an increase or a decrease in temperature (0.05℃/day) following a warm period (mean temperature ≥26℃) was associated with the onset of cluster periods. In contrast, a greater increase in temperature (0.15℃/day) following a cold period (mean temperature < 21℃) was needed to evoke cluster periods. No such associations were found following moderate periods (21℃ ≤mean temperature <26℃). Our study shows that temperature is associated with precipitating or priming cluster periods. The influence depends on the temperature of the preceding periods.

Cortical plasticity in episodic and chronic cluster headache.

Cluster headache (CH) is characterized by recurrent episodes of excruciatingly painful, unilateral headache attacks typically accompanied by trigeminal autonomic symptoms. Due to its rhythm with alternating episodes of pain and no-pain, it is an excellent model to investigate whether structural brain changes detected by magnetic resonance based voxel-based-morphometry (VBM) reflect the cause of the disease, may be a consequence of the underlying disease other than pain, or may simply be caused by the sensation of pain itself. We investigated 91 patients with CH in different stages of their disease using VBM and compared them to 78 age- and gender-matched healthy controls. We detected distinct regional gray matter (GM) changes in different brain regions including the temporal lobe, the hippocampus, the insular cortex and the cerebellum. The extent, location and direction of observed GM alterations depended on the state of disease and appeared dynamic in relation to pain state (i.e., pain vs. no-pain). No hypothalamic changes were detected in CH patients compared to healthy controls. The GM changes observed in this study are highly dynamic and thereby reflect the cortical plasticity of the brain in regard to pain. This observed dynamic may provide an explanation of the diverse results of previous VBM studies in pain. Regarding CH the results suggest that the disease is more likely to be caused by a network dysfunction rather than by a single malfunctioning structure.

Greater occipital nerve blocks in chronic cluster headache: a prospective open‐label study

Greater occipital nerve blockade (GONB) has been shown to be effective in episodic cluster headache. However, its use in chronic cluster headache (CCH) is less certain. The study aims to prospectively assess the efficacy and consistency of response to GONB in a large series of CCH patients. CCH patients who had a unilateral GONB and were referred to the National Hospital for Neurology and Neurosurgery were studied prospectively. Headache characteristics were collected using headache diaries. Responders were considered to be patients with a complete or partial response lasting at least 7 days. In a subgroup of responders the outcomes of serial GONB performed at 3-monthly intervals were also analysed. Eighty-three CCH patients were studied. After the first GONB, a positive response was observed in 47 (57%) patients: 35 (42%) were rendered pain free, 12 (15%) had a partial benefit and one patient obtained <50% improvement. The duration of a positive response lasted a median of 21 days (range 7-504 days). There was a transient worsening of condition in 6% of patients. The overall rate and average duration of response remained consistent after the second [n = 37; 31 responders (84%); median duration 21 days], third [n = 28; 20 responders (71%); median duration 25 days] and fourth [n = 14; 10 responders (71%); median duration 23 days] injections. GONB seems to be an efficacious treatment with reproducible effects in CCH patients. Performed three monthly, GONB may have a useful role in the management of CCH.

Insomnia and Periodicity of Headache in an Arctic Cluster Headache Population

To assess the prevalence of chronic insomnia and the periodicity of headache attacks in an Arctic cluster headache population. Cluster headache is a sleep-related disorder, and attacks have both circadian and circannual rhythmicity. Through a retrospective hospital chart review, we identified all subjects diagnosed with episodic cluster headache (ICD-10 G 44.0) at the Neurological Departments in Northern Norway (located north of 66°33'N) between January 1, 2000 and December 31, 2010. Patients with a confirmed diagnosis (ICHD-2) received a comprehensive questionnaire covering demographic data, clinical characteristics, sleep, and periodicity of attacks. A total of 196 subjects were registered, and 178 received the questionnaire. The response rate was 88/178 (49%). Fifty-eight men (aged 49.2 ± 13.6) and 12 women (aged 49.7 ± 15.5) were included. Forty percent of the responders suffered from chronic insomnia (Diagnostic and Statistical Manual of Mental Disorders 4th edition). Forty-nine percent of the responders and 42% of the non-responders were shift workers, which is much higher than compared with the general population (24%). Insomnia was significantly associated with shift work and experiencing longer-lasting cluster bouts. One third attributed their insomnia to the cluster headache. Thirty-seven percent reported a seasonal predilection of the cluster periods, and 58% a diurnal periodicity of attacks. Eighty percent often or always had headache attacks during sleep, the most frequent time interval being at 12:00-4:00 am. Shift workers were significantly more likely to see lack of sleep as a cluster attack trigger than daytime workers. Chronic insomnia and shift work seem to be common among Arctic cluster headache patients. The small number of subjects included in this study implies that conclusions should be drawn with caution, but the findings support the idea of cluster headache as a circadian rhythm disorder.

Carotid dissection mimicking a new attack of cluster headache

BackgroundSymptomatic cluster headache (CH) secondary to internal carotid artery dissection (ICAD) has been frequently reported, however, as far as we know, the coexistence of episodic CH and acute symptomatic CH secondary to ICAD has not.Case reportA 39 year-old man, affected by episodic CH since the age of 19, presented an atypical headache associated with his usual autonomic symptoms. After a series of negative tests, MRA eventually revealed dissection of the right distal internal carotid artery.Discussion and conclusionsThe coexistence of episodic CH and acute CH symptomatic of ICAD in our patient suggests that, at least in some cases, CH and ICAD may be different expressions of a common underlying cause: hidden vessel wall damage. When risk factors and the change - though partial - of clinical features suggest symptomatic cases, CH patients have to be strictly monitored over time. Given the lack of a gold standard investigation for dynamic diseases such as dissections, these patients require multimodal diagnostic investigation over time, even in cases where exams are normal at onset.

Spotlight on the October 1 Issue

Plasma samples were assessed from 103 women with chronic migraine, 31 controls, 43 women with episodic migraine, and 14 patients with episodic cluster headache. Increased CGRP level measured in peripheral blood outside migraine attacks and in the absence of symptomatic medication could be a biomarker aiding the diagnosis of chronic migraine. See p. 1191; Editorial, p. 1184 The authors performed a clinicoserologic study of 163 patients with neuromyelitis optica. Cell-based assays were most sensitive for AQP4-IgG detection; further, the timing of blood draws and immunosuppressant therapy influenced serostatus. Disability outcome was more favorable for patients in the …

Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine

To determine calcitonin gene-related peptide (CGRP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM). Women older than 17 years and diagnosed with CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. CGRP levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before. For ethical reasons, preventatives were not stopped. We assessed plasma samples from 103 women with CM, 31 matched healthy women, 43 matched women with EM, and 14 patients with episodic cluster headache matched for age. CGRP levels were significantly increased in CM (74.90 pg/mL) as compared with control healthy women (33.74 pg/mL), women with EM (46.37 pg/mL), and patients with episodic cluster headache (45.87 pg/mL). Thresholds of 43.45 and 58.22 pg/mL optimize the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. In the CM group, CGRP levels were significantly increased in women with a history of migraine with aura vs those only experiencing migraine without aura. Variables such as age, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption, or kind of preventative treatment did not significantly influence CGRP levels. Increased CGRP level measured in peripheral blood outside migraine attacks and in the absence of symptomatic medication could be a biomarker helping in the diagnosis of CM.

Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil

BackgroundEpisodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode.Methods and designPredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH.DiscussionPredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil.Trial registrationGerman Clinical Trials Register DRKS00004716