The clinical characteristics of familial cluster headache

BACKGROUND: A positive family history predisposes to the development of cluster headache. The distinct characteristics of familial cluster headache have yet to be confirmed, however, evidence suggests a younger age of onset and higher proportion of females in this subgroup. OBJECTIVES: To assess the rate and mode of inheritance of familial cluster headache in a tertiary referral centre for headache. To describe the clinical features of familial cluster headache. METHODS: A retrospective study conducted between 2007 and 2017. Cluster headache was confirmed in probands and affected relatives. Differences in demographics, clinical characteristics, and response-to-treatment in familial cluster headache were delineated through multivariate analysis using a control cohort of 597 patients with sporadic cluster headache. RESULTS: Familial cluster headache was confirmed in 48 (7.44%) patients and predominantly reflected an autosomal dominant mode of inheritance with reduced penetrance. Familial cases were more likely to report nasal blockage (OR 4.06, 95% CI; 2.600-6.494, p < 0.001) during an attack and a higher rate of concurrent short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (OR 3.76, 95% CI; 1.572-9.953, p = 0.004). CONCLUSION: These findings add to evidence suggesting a genetic component to cluster headache. Here, we demonstrated prominent nasal blockage, and a higher occurrence of concomitant short-lasting unilateral neuralgiform headache with conjunctival injection and tearing in this subgroup, further delineating the phenotype

日本におけるSUNCT/SUNAの臨床像 : クリニックベースの研究

Objectives:This study aimed to report the clinical profiles of patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/short-lasting unilateral neuralgiform headache attacks with cranial autonomic (SUNA) in a Japanese population by surveying those enrolled at a regional headache center in Japan.Methods:In this consecutive case series study, the clinical characteristics of patients with SUNCT (eight men, three women; mean age: 59.5 ± 20.5 years) and SUNA (five men, four women; mean age: 51.3 ± 18.4 years) who visited Tominaga Hospital from February 2011 to January 2017 were examined. Headaches were diagnosed according to the International Classification of Headache Disorders, Third edition (ICHD-3) guidelines.Results:Brief clusters of separate attacks were reported by all patients. The mean duration of attacks was 91.9 ± 87.9 s. Ipsilateral rhinorrhea was observed in 9 of 20 (45.0%) cases and facial sweating was observed in 1 of 20 (5.0%) cases. An eminent response to lamotrigine was observed in 9 of 9 (100%) patients; however, adverse events were only reported in 2 of 9 (22.2%) cases. An intravenous infusion of lidocaine was demonstrated to be completely successful for short-term prevention in 5 of 6 (83.3%) SUNCT cases.Conclusions:Lamotrigine can successfully treat most patients, and intravenous lidocaine is useful for the short-term preventive therapy of severe recalcitrant attacks in Japanese patients with SUNCT/SUNA.博士（医学）・乙第1437号・令和元年9月27日Copyright © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage)

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor

PRIMARY SJÖGREN SYNDROME PATIENT PRESENTING CENTRAL NERVOUS SYSTEM MANIFESTATIONS SUCCESSFULLY TREATED WITH CORTICOSTEROIDS

We treated a case of primary Sjören's syndrome with progressive central nervous systems manifestations. Central nervous system involvement in such patients is difficult to diagnose and rarely described. A 71-year-old man presenting with vertigo and vomiting was admitted to our hospital. Intension tremor developed in the left extremities and gradually spread to the right extremities, while an articulation disorder also appeared. Results of T2-weighted cranial magnetic resonance imaging on admission showed abnormally high intensity areas in the pons, medulla oblongata, and cerebellum, nearly all of which were on the left side. Laboratory findings showed a high level of serum γ-globulin, and were positive antinuclear antibodies, anti-Ro antibodies, and anti-La antibodies, while histological findings of a minor salivary gland biopsy revealed focal sialadenitis with marked lymphocytic infiltration. These serological and histopathological findings confirmed that the patient had primary Sjören's syndrome. The patient underwent pulsed intravenous methylprednisolone therapy, and blepharoptosis, miosis, kinetic tremors improved with the therapy. In addition, the intensities in T2-weighted cranial MR images in the pons and medulla oblongata disappeared, and cerebellar intensity improved. In view of the underlying autoimmune disorder, it seemed likely that the etiology of the CNS symptoms was related to inflammatory brain changes, such as from autoimmune-related vasculitis

Clinical profile of SUNCT/SUNA in Japan: A clinic-based study.

Objectives:This study aimed to report the clinical profiles of patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/short-lasting unilateral neuralgiform headache attacks with cranial autonomic (SUNA) in a Japanese population by surveying those enrolled at a regional headache center in Japan.Methods:In this consecutive case series study, the clinical characteristics of patients with SUNCT (eight men, three women; mean age: 59.5 ± 20.5 years) and SUNA (five men, four women; mean age: 51.3 ± 18.4 years) who visited Tominaga Hospital from February 2011 to January 2017 were examined. Headaches were diagnosed according to the International Classification of Headache Disorders, Third edition (ICHD-3) guidelines.Results:Brief clusters of separate attacks were reported by all patients. The mean duration of attacks was 91.9 ± 87.9 s. Ipsilateral rhinorrhea was observed in 9 of 20 (45.0%) cases and facial sweating was observed in 1 of 20 (5.0%) cases. An eminent response to lamotrigine was observed in 9 of 9 (100%) patients; however, adverse events were only reported in 2 of 9 (22.2%) cases. An intravenous infusion of lidocaine was demonstrated to be completely successful for short-term prevention in 5 of 6 (83.3%) SUNCT cases.Conclusions:Lamotrigine can successfully treat most patients, and intravenous lidocaine is useful for the short-term preventive therapy of severe recalcitrant attacks in Japanese patients with SUNCT/SUNA.博士（医学）・乙第1437号・令和元年9月27日Copyright © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).identifier:Cephalalgia Reports Vol.2 p.1-6 (2019 Feb 20)identifier:25158163identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3673identifier:Cephalalgia Reports, 2: 1-

Is pituitary MRI screening necessary in cluster headache?

Objective To determine the prevalence and clinical predictors of pituitary adenomas in cluster headache patients, in order to determine the necessity of performing dedicated pituitary magnetic resonance imaging in patients with cluster headache. Methods A retrospective study was conducted of all consecutive patients diagnosed with cluster headache and with available brain magnetic resonance imaging between 2007 and 2017 in a tertiary headache center. Data including demographics, attack characteristics, response to treatments, results of neuroimaging, and routine pituitary function tests were recorded. Results Seven hundred and eighteen cluster headache patients attended the headache clinic; 643 underwent a standard magnetic resonance imaging scan, of whom 376 also underwent dedicated pituitary magnetic resonance imaging. Pituitary adenomas occurred in 17 of 376 patients (4.52%). Non-functioning microadenomas (n = 14) were the most common abnormality reported. Two patients, one of whom lacked the symptoms of pituitary disease, required treatment for their pituitary lesion. No clinical predictors of those adenomas were identified after multivariate analysis using random forests. Systematic pituitary magnetic resonance imaging scanning did not benefit even a single patient in the entire cohort. Conclusion The prevalence of pituitary adenomas in cluster headache is similar to that reported in the general population, thereby precluding an over-representation of pituitary lesions in cluster headache. We conclude that the diagnostic assessment of cluster headache patients should not include specific pituitary screening. Only patients with standard brain magnetic resonance imaging findings or symptoms suggestive of a pituitary disorder require brain magnetic resonance imaging with dedicated pituitary views

sj-xlsx-3-cep-10.1177_03331024231156925 - Supplemental material for Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists’ diagnostic accuracy

Supplemental material, sj-xlsx-3-cep-10.1177_03331024231156925 for Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists’ diagnostic accuracy by Masahito Katsuki, Tomokazu Shimazu, Shoji Kikui, Daisuke Danno, Junichi Miyahara, Ryusaku Takeshima, Eriko Takeshima, Yuki Shimazu, Takahiro Nakashima, Mitsuhiro Matsuo and Takao Takeshima in Cephalalgia</p

sj-pdf-1-cep-10.1177_03331024231156925 - Supplemental material for Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists’ diagnostic accuracy

Supplemental material, sj-pdf-1-cep-10.1177_03331024231156925 for Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists’ diagnostic accuracy by Masahito Katsuki, Tomokazu Shimazu, Shoji Kikui, Daisuke Danno, Junichi Miyahara, Ryusaku Takeshima, Eriko Takeshima, Yuki Shimazu, Takahiro Nakashima, Mitsuhiro Matsuo and Takao Takeshima in Cephalalgia</p

sj-pdf-2-cep-10.1177_03331024231156925 - Supplemental material for Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists’ diagnostic accuracy

Supplemental material, sj-pdf-2-cep-10.1177_03331024231156925 for Developing an artificial intelligence-based headache diagnostic model and its utility for non-specialists’ diagnostic accuracy by Masahito Katsuki, Tomokazu Shimazu, Shoji Kikui, Daisuke Danno, Junichi Miyahara, Ryusaku Takeshima, Eriko Takeshima, Yuki Shimazu, Takahiro Nakashima, Mitsuhiro Matsuo and Takao Takeshima in Cephalalgia</p