scholarly journals Evidence That HFE H63D Variant Is a Potential Disease Modifier in Cluster Headache

2021 ◽  
Author(s):  
Maria Papasavva ◽  
Michail Vikelis ◽  
Martha-Spyridoula Katsarou ◽  
Vasileios Siokas ◽  
Emmanouil Dermitzakis ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Primary Headache ◽  
Headache Disorder ◽  
Allelic Frequency ◽  
Primary Headaches ◽  
Primary Headache Disorder ◽  
Disease Modifier ◽  
Potential Link

AbstractCluster headache (CH) is a primary headache disorder with a complex genetic background. Several studies indicate a potential link between iron homeostasis and the pathophysiology of primary headaches. The HFE gene encodes for a protein involved in iron metabolism, while genetic variants in HFE have been associated with hereditary hemochromatosis (HH), an iron overload disorder. The objective of the current study was to examine the association of the more common HFE H63D variant, with the susceptibility to develop CH and diverse clinical phenotypes in a population of Southeastern European Caucasian (SEC) origin. Genomic DNA samples from 128 CH patients and 294 neurologically healthy controls were genotyped for the HFE rs1799945 (H63D) variant. H63D genotypic and allelic frequency distribution did not differ significantly between patients and controls (p > 0.05). Subgroup analysis revealed a significantly more frequent occurrence of the variant G allele in chronic compared to episodic CH patients, indicative for a possible correlation of the HFE gene with the susceptibility for disease chronification. Although homozygosity for the less prevalent H63D variant G allele was minimal in the CH cohort, the results of the present study are in accordance with previous studies in CH and migraine patients, suggesting that HFE H63D variant modifies the disease clinical characteristics. Hence, despite the absence of a per se association with CH susceptibility in the current SEC cohort, variability in HFE gene may be potentially regarded as a disease modifier genetic factor in CH.

Genetics of cluster headache

Cephalalgia ◽  
2019 ◽  
Vol 39 (10) ◽  
pp. 1298-1312 ◽  
Author(s):  
Kate F Gibson ◽  
Anita Dos Santos ◽  
Nunu Lund ◽  
Rigmor Jensen ◽  
Ioannis M Stylianou
Keyword(s):  
Cluster Headache ◽  
Candidate Gene ◽  
Gene Selection ◽  
Association Studies ◽  
Twin Studies ◽  
Primary Headache ◽  
Headache Disorder ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
Primary Headache Disorder

Background Cluster headache is the most severe primary headache disorder. A genetic basis has long been suggested by family and twin studies; however, little is understood about the genetic variants that contribute to cluster headache susceptibility. Methods We conducted a literature search of the MEDLINE database using the PubMed search engine to identify all human genetic studies for cluster headache. In this article we provide a review of those genetic studies, along with an overview of the pathophysiology of cluster headache and a brief review of migraine genetics, which have both been significant drivers of cluster headache candidate gene selection. Results The investigation of cluster headache genetic etiology has been dominated by candidate gene studies. Candidate selection has largely been driven by the pathophysiology, such as the striking rhythmic nature of the attacks, which spurred close examination of the circadian rhythm genes CLOCK and HCRTR2. More recently, unbiased genetic approaches such as genome-wide association studies (GWAS) have yielded new genetic avenues of interest including ADCYAP1R1 and MME. Conclusions The majority of candidate genes studied for cluster headache suffer from poor reproducibility. Broader genetic interrogation through larger unbiased GWAS, exome, and whole genome studies may provide more robust candidates, and in turn provide a clearer understanding of the causes of cluster headache.

Headache

2015 ◽  
Author(s):  
Peter J. Goadsby
Keyword(s):  
Cluster Headache ◽  
Severe Pain ◽  
Primary Headache ◽  
Headache Disorder ◽  
Headache Disorders ◽  
Important Work ◽  
Pain Experience ◽  
Global Impact ◽  
Primary Headache Disorder ◽  
The World

Headache disorders are the dominant cause of neurological disability in the world and the most common reason for neurological referral in any country studied. Yet for much of the first half the twentieth century, research was mired in peripheral mechanistic sideshows. Migraine, the most common disabling primary headache disorder, has been established as primarily a brain problem, with important advances in classification, treatment, and biological understanding. Cluster headache, perhaps the most severe pain experience of humans, has found its nidus in the diencephalon; treatments are evolving and biology being unravelled. Contributions to headache disorders resonate across humanity, so important work here has a global impact for good.

scholarly journals Update on Treatment of Cluster Headache

2021 ◽  
Vol 39 (3) ◽  
pp. 113-120
Author(s):  
Jong-Hee Sohn ◽  
Mi Ji Lee ◽  
Soo-Jin Cho
Keyword(s):  
Cluster Headache ◽  
Preventive Treatment ◽  
Primary Headache ◽  
Headache Disorder ◽  
Preventive Therapy ◽  
Systemic Steroid ◽  
Novel Treatments ◽  
Primary Headache Disorder ◽  
Cranial Autonomic Symptoms ◽  
High Flow Oxygen

Cluster headache (CH) is characterized by severe unilateral short-lasting headache attacks, accompanying ipsilateral cranial autonomic symptoms or the sense of restlessness and agitation, or both. CH is a highly disabling primary headache disorder but often not optimally treated. High-flow oxygen and parenteral triptans are the most effective treatment to treat an acute CH attack. Transitional treatments include systemic steroid therapy and sub-occipital steroid injection. For preventive therapy, verapamil and lithium are recommended as first-line treatments. Novel treatments have appeared, such as neuromodulation and medication targeting calcitonin gene-related peptide (CGRP) or its receptor. Galcanezumab, the only anti-CGRP receptor monoclonal antibody with proven efficacy for the preventive treatment of episodic CH, represents an important advance for pharmacological treatment of CH. Neuromodulation strategies, such as the non-invasive vagus nerve stimulation and the sphenopalatine ganglion stimulation, have been proven effective in reducing the intensity and frequency of attacks, and also to be safe and well tolerated.

scholarly journals Failure to identify underlying autoimmunity and primary headache disorder might be the reasons for refractoriness of trochlear headaches

2020 ◽  
Vol 3 ◽  
pp. 251581632095177
Author(s):  
Pawan Ojha ◽  
Vikram Aglave ◽  
Suranjana Basak ◽  
Jayendra Yadav
Keyword(s):  
Primary Headache ◽  
Headache Disorder ◽  
Tension Type Headache ◽  
Prior History ◽  
Primary Headaches ◽  
Primary Headache Disorder ◽  
Local Injections ◽  
Poor Outcomes ◽  
Type Headache ◽  
A Minor

Introduction: A better understanding of etiology might improve poor outcomes of trochlear headaches (TRHs). Aims: To study clinical spectrum, etiology, and therapeutic response of TRH. Methods: Fifty-three TRH patients seen in a single center between 2015 and 2020 were included, excluding Trigeminal Autonomic Cephalalgia (TAC). Results: Mean age was 36.45 years (range 11–85 years), with 77.35% being females. Twenty-five patients had continuous trochlear headache (CTRH) and 28 episodic trochlear headache (ETRH). Tension-type headache (TTH) occurred in 9 ETRH patients and 24 of 25 CTRH patients, and migraine-like headaches occurred in 19 ETRH patients and 8 CTRH (trochlear migraine) patients. Prior history of headaches was noted in 22 of 28 ETRH and 11 of 25 CTRH patients. Twenty-eight responded to migraine/TTH prophylaxis, 25 being nonresponders (partial/no response). Fourteen of 25 nonresponders, 4 of 28 responders (4 of 4 secondary and 5 of 9 idiopathic trochleitis (IT), 3 of 9 primary TRH (PTRH), and 6 of 28 ETRH) had autoantibodies, that is, 11 antinuclear antibodies (ANAs) and 7 antithyroid antibodies. Ten of 14 (71.42%) antibody-positive nonresponders improved with immunosuppressants including steroids/hydroxychloroquine and only 11 required local injections. Finally, 38 patients had good response, 13 partial, and 2 no response. The etiology and refractoriness of IT can be attributed to underlying autoimmunity and a minor contribution by primary headaches, vice versa being the case for PTRH and ETRH. Refractory TRHs should be evaluated for underlying autoimmunity and primary headaches. Conclusion: Identification and treatment of underlying autoimmunity and primary headaches can help improve outcome of TRH.

A Comparative Analysis of Amytripiline, Flunnarazine and Topiramate in the treatment of Primary Headache

2021 ◽  
Vol 18 (2) ◽  
pp. 45-48
Author(s):  
Babu Ram Pokharel ◽  
Gopal Raman Sharma ◽  
Prabhaw Upadhyaya ◽  
Samip Jung Budhathoki ◽  
Santosh Thapa ◽  
...  
Keyword(s):  
Impact Test ◽  
Primary Headache ◽  
Headache Disorder ◽  
Categorical Variables ◽  
Primary Headaches ◽  
Chi Square ◽  
Headache Patient ◽  
Primary Headache Disorder ◽  
Chi Square Test ◽  
Headache Impact

Introduction Primary headache disorder, characterized by recurrent headache is the most prevalent disease leading to widespread ill health and impaired quality of life. In Nepal headache is one of the most common cause of patient attending neurology clinic. Amitriptyline, Flunarizine and Topiramate are common drugs in the treatment of primary headache. We conducted this study to compare the efficacy of drugs namely Amitriptyline, Flunarizine and Topiramate in the treatment of primary headache Materials and Methods This is the retrospective data analysis of primary headache patient treated with amitriptyline, flunarizine and topiramate. On their first, second and third subsequent visits, Headache Impact Test 6 Scoring was done by a medical person. Patient were treated clinically. After third follow up data were analyzed using SPSS version 20.0. Categorical variables were compared by chi-square test, paired sample t-test, ANOVA test and Welch test. Results A total of 142 patient data was analyzed. The most common age group were between 20 to 39 years (56.34%) followed by 40 to 59 years (33.80%). Female were predominant in the group 124 (87.32%).  All three medication Amitriptyline, Flunarizine and Topiramate were able to significantly lower Headache impact test  -17.23 ± 6.643, -14.06 ± 7.155, -15.82 ± 5.907 respectively (P- <0.001). Amitriptyline was found to be better than other two drugs in reducing Headache Impact Test. Conclusion All three drugs namely Amitriptyline, Flunarizine and Topiramate, are significantly effective in the treatment of primary headache. Though tension type of headache is the most common type of headache, amitriptyline seems to be equally effective in treatment with other primary headaches.

CACNA1A Gene Polymorphisms in Cluster Headache

Cephalalgia ◽  
2001 ◽  
Vol 21 (10) ◽  
pp. 953-958 ◽  
Author(s):  
C Sjöstrand ◽  
V Giedratis ◽  
K Ekbom ◽  
E Waldenlind ◽  
J Hillert
Keyword(s):  
Cluster Headache ◽  
Primary Headache ◽  
Headache Disorder ◽  
Familial Hemiplegic Migraine ◽  
Hemiplegic Migraine ◽  
Promising Candidate ◽  
Primary Headache Disorder ◽  
Increased Risk ◽  
Ihs Criteria ◽  
Cacna1a Gene

Cluster headache (CH) is a primary headache disorder where the aetiological and pathophysiological mechanisms still are largely unknown. An increased risk of CH in first- and second-degree relatives suggests the importance of genetic factors. Mutations of the P/Q type calcium channel alpha 1 subunit (CACNA1A) gene on chromosome 19p13 have been shown to cause several neurological disorders with a wide clinical spectrum, mainly episodic diseases. Missence mutations of the gene cause familial hemiplegic migraine (FHM) and it is also likely to be involved in the more common forms of migraine. The CACNA1A gene is thus a promising candidate gene for CH. In this study we performed an association analysis of an intragenic polymorphic (CA)n-repeat with marker D19S1150 and a (CAG)n-repeat in the 3′UTR region, in 75 patients with CH according to IHS criteria and 108 matched controls. Genotypes and allele frequencies were similarly distributed in patients and controls. Linkage disequilibrium between the two markers was similar in patients and controls. We conclude that an importance of the CACNA1A gene in sporadic CH is unlikely.

Prevalence of Primary Headache Disorders in Kuwait

2017 ◽  
Vol 48 (3-4) ◽  
pp. 138-146 ◽  
Author(s):  
Jasem Yousef Al-Hashel ◽  
Samar Farouk Ahmed ◽  
Raed Alroughani
Keyword(s):  
Medication Overuse Headache ◽  
Primary Headache ◽  
Headache Disorder ◽  
Episodic Migraine ◽  
Tension Type Headache ◽  
Primary Headaches ◽  
Primary Headache Disorder ◽  
Work Related ◽  
Primary Headache Disorders ◽  
Kuwaiti Population

Background: Only an insignificant quantum of data exists on the prevalence of primary headaches among those living in Kuwait. We aimed to determine the prevalence of primary headaches among the Kuwaiti population. Methods: This community-based study included Kuwaiti population aged 18-65 years. Using systematic random sampling, data was collected by the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation questionnaire. Responses to the diagnostic questions were transformed into diagnoses algorithmically to confirm the diagnosis of primary headache. Results: A total of 15,523 patients were identified of whom 9,527 (61%) were diagnosed with primary headache disorder; a female predominance of 62.2% was observed. The mean age was 34.84 ± 10.19. Tension-type headache (TTH) was the most prevalent at 29% followed by episodic migraine (23.11%), chronic migraine (5.4%), and medication overuse headache (2.4%). Primary headache prevalence declined steadily from 71% in those aged 18-30 years to 23% in those over 50 (p < 0. 037). The female:male ratio was 1.7:1. Frequency and severity of primary headache were correlated significantly with lost work days (r = 0.611, p < 0.001 and r = 0.102, p = 0.001, respectively). Conclusions. In Kuwait, primary headache disorder is more frequent in young adults and females. TTH followed by episodic migraine were the more prevalent types of headache. Higher frequency and severe headaches were associated with increasing social and work-related burden.

Cluster headache

2020 ◽  
pp. 182-189
Author(s):  
Ilse F. de Coo ◽  
Leopoldine A. Wilbrink ◽  
Joost Haan
Keyword(s):  
Nervous System ◽  
Cluster Headache ◽  
Sensory System ◽  
Primary Headache ◽  
Headache Disorder ◽  
Primary Headache Disorder ◽  
Oxygen Inhalation ◽  
First Choice ◽  
Temporal Course ◽  
Subcutaneous Sumatriptan

Cluster headache is a primary headache disorder characterized by attacks of severe-to-very severe unilateral pain, located in the orbital, supraorbital, and/or temporal regions, with ipsilateral autonomic symptoms and/or restlessness. By definition, cluster headache attacks last between 15 and 180 minutes. Based on the temporal course, cluster headache can be categorized into episodic and chronic. A subdivision can also be made in primary and secondary chronic and secondary episodic. The cause of cluster headache is unknown, but probably the hypothalamus, trigeminal sensory system, some cranial blood vessels, and the autonomic nervous system are involved. A combination of acute (oxygen inhalation and/or subcutaneous sumatriptan) and prophylactic (first choice verapamil) treatment is usually necessary. For treatment-resistant patients, some experimental invasive options exist.

Pathophysiology of hypnic headache

Cephalalgia ◽  
2014 ◽  
Vol 34 (10) ◽  
pp. 806-812 ◽  
Author(s):  
Dagny Holle ◽  
Steffen Naegel ◽  
Mark Obermann
Keyword(s):  
Electrophysiological Study ◽  
Primary Headache ◽  
Headache Disorder ◽  
Primary Headaches ◽  
Hypnic Headache ◽  
Primary Headache Disorder ◽  
Study Results ◽  
Symptomatic Headache ◽  
Underlying Mechanisms ◽  
Underlying Pathophysiology

Background Hypnic headache (HH) is a rare primary headache disorder that is characterized by strictly sleep related headache attacks. Purpose The underlying pathophysiology of HH is mainly enigmatic but some clinical characteristics such as circadian rhythmicity and caffeine responsiveness may point toward possible underlying mechanisms. Method Current studies that deal with the pathophysiology of HH are summarized. Data on cerebral imaging, sleep, electrophysiology studies, effectiveness of drugs, and symptomatic headache types are discussed to illuminate underlying pathophysiologic mechanisms. Conclusion HH can be clearly differentiated by its clinical presentation as well as imaging and electrophysiological study results from other primary headaches such as migraine or cluster headache. The underlying pathophysiology is still enigmatic but a hypothalamic involvement seems to be likely.

Device review: Pulsante™ sphenopalatine ganglion microstimulator

2019 ◽  
Vol 9 (6) ◽  
pp. 535-541
Author(s):  
Nenna Nwazota ◽  
Srinivas Pyati ◽  
Kyle Fisher ◽  
Lance Roy
Keyword(s):  
Remote Control ◽  
Cluster Headache ◽  
Treatment Option ◽  
Primary Headache ◽  
Headache Disorder ◽  
Sphenopalatine Ganglion ◽  
Primary Headache Disorder ◽  
Fixation Plate ◽  
Stimulating Electrodes ◽  
Autonomic Reflex

Cluster headache (CH) is a primary headache disorder. The use of neuromodulation in treatment of CH is well documented. The sphenopalatine ganglion (SPG) has long been a target for management of CH. Intervention at the level of the SPG can interrupt the trigemino-autonomic reflex, which mediates CH pain. The Pulsante system is the only device on the market created for SPG stimulation. The Pulsante device consists of the device body, a lead with six stimulating electrodes placed in the pterygopalatine fossa, and a fixation plate to allow anchoring of the device to the maxilla. Stimulation is administered via a patient-controlled handheld remote control held over the cheek. SPG stimulation is an important treatment option for CH patients.

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