Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Association between Oxidative Balance Score and Severe Headache or Migraine among American Adults A Cross-Section Study.

BACKGROUND: Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored. OBJECTIVE: We aimed to examine the relationship between OBS and severe headaches or migraines among American adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation. RESULTS: The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively. CONCLUSION: The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.

Association between migraine and cardiovascular disease mortality: A prospective population-based cohort study.

OBJECTIVE: The study assessed the association between migraine and cardiovascular disease (CVD) mortality in the US population. BACKGROUND: Previous studies have drawn different conclusions about the association between migraine and CVD mortality based on different populations; therefore, it is important to explore the relationship between migraine and CVD mortality in the US population. METHODS: This prospective cohort study included 10,644 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Participants who reported having severe headache or migraine were classified as having migraine. Mortality data were obtained by linkage of the cohort database to the National Death Index as of December 31, 2019. Based on the International Classification of Diseases, Tenth Revision, CVD mortality includes the following disease codes: I00-I09 (acute rheumatic fever and chronic rheumatic heart diseases), I11 (hypertensive heart disease), I13 (hypertensive heart and renal disease), I20-I25 (ischemic heart diseases), I26-I28 (pulmonary embolism and other acute pulmonary heart diseases), I29 (various cardiovascular diseases caused by different reasons), I30-I51 (other forms of heart disease), and I60-I69 (cerebrovascular diseases). Data were analyzed from October to November 2022. RESULTS: Among 10,644 adults included in the study (mean age, 46.4 [0.3] years, 5430 men [47.4%]), 2106 (20.4%) had migraine. During a median follow-up period of 201 months, there were 3078 all-cause deaths and 997 CVD deaths. Compared to individuals without migraine, those with migraine had an adjusted hazard ratio (HR) of 1.30 (95% confidence interval [CI], 1.04-1.62; p = 0.019) for CVD mortality and 1.23 (95% CI, 1.13-1.35; p < 0.001) for all-cause mortality. In subgroup analyses, migraine was associated with CVD mortality in participants who were women (HR, 1.43; 95% CI, 1.06-1.93), aged < 45 years (HR, 1.69; 95% CI, 1.04-2.76), non-Hispanic White (HR, 1.42; 95% CI, 1.09-1.86), those with a body mass index < 30 kg/m2 (HR, 1.36; 95% CI, 1.03-1.78), former or current smokers (HR, 1.36; 95% CI, 1.00-1.85), former or current alcohol drinkers (HR, 1.33; 95% CI, 1.03-1.72), and those without metabolic syndrome (HR, 1.31; 95% CI, 1.01-1.71). The association between migraine and CVD mortality was robust in sensitivity analyses, after excluding participants who died within 2 years of follow-up (HR, 1.31; 95% CI, 1.05-1.65) or those with a history of cancer at baseline (HR, 1.28; 95% CI, 1.01-1.62). CONCLUSIONS: Migraine was associated with a higher CVD mortality rate in the US population.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

Association between inflammatory potential of diet and self-reported severe headache or migraine: A cross-sectional study of the National Health and Nutrition Examination Survey.

OBJECTIVE: Inflammation plays an important role in migraine development. Dietary interventions that reduce the inflammatory state are effective for migraine prophylaxis. However, little is yet known about the association between the inflammatory potential of diet and migraine in the general US adult population. The aim of this study was to evaluate whether the inflammatory potential of diet is associated with severe headache or migraine in US adults. METHODS: This cross-sectional study analyzed data from adult participants in the 1999-2004 National Health and Nutrition Examination Survey. Severe headache or migraine was determined based on self-reported information. Severe headache or migraine was defined as an affirmative response to the question: "Have you had a severe headache or migraine in the past 3 mo?" The dietary inflammatory index (DII) was used to assess the inflammatory potential of the diet. Multivariable logistic regression models were used to determine the odds ratio (OR) and 95 % confidence interval (95% CI) for the association between DII and severe headache or migraine. A multivariable-adjusted restricted cubic spline model was constructed to establish the OR curves at 3 knots to examine the possible non-linear dose-response association between DII and severe headache or migraine. RESULTS: Of 10359 participants included in this study (mean age, 46.3 [0.3] y; 5116 [49%] men), 2083 (22%) reported previous episodes of severe headache or migraine, whereas 8276 (78%) did not. After adjusting for potential confounders, the DII score was associated with severe headache or migraine (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03-1.15; P = 0.003). Compared with participants with the lowest tertile (T1) of DII score (i.e., T1; ≤-4.42 to ≤0.77), those with the highest tertile (i.e., T3; <2.44 to ≤5.18) had an adjusted OR for severe headache or migraine of 1.46 (95% CI, 1.20-1.77; P < 0.001). The multivariable restricted cubic spline showed a non-linear association between DII and severe headache or migraine (P = 0.012). In two piecewise regression models, the adjusted OR of developing a severe headache or migraine was 1.19 (95% CI, 1.04-1.37; P = 0.012) in participants with a DII score ≥1.48, whereas there was no association between DII and severe headache or migraine in participants with a DII score <1.48. Subgroup analyses showed that DII was associated with severe headache or migraine in women (OR, 1.73; 95% CI, 1.31-2.28), individuals 20 to 50 y of age (OR, 1.66; 95% CI, 1.29-2.14), those who were married or living with a partner (OR, 1.49; 95% CI, 1.19-1.85), individuals living alone (OR, 1.36; 95% CI, 1.02-1.81), those with a high level of education (OR, 1.72; 95% CI, 1.26-2.36), individuals with a low family income (OR, 1.58; 95% CI, 1.10-2.28), those with a medium or high family income (OR, 1.48; 95% CI, 1.17-1.86), and body mass index <25 kg/m2 (OR, 1.71; 95% CI, 1.21-2.41). CONCLUSION: The inflammatory potential of the diet is associated with severe headache or migraine in US adults.

The prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache: The survey of fibromyalgia comorbid with headache.

OBJECTIVE: The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache. BACKGROUND: Studies done in non-Chinese populations suggest that around one-third of patients with primary headache have fibromyalgia, but data from mainland China are limited. Investigations into the prevalence and clinical features of fibromyalgia in Chinese patients with primary headache would improve our understanding of these two complex disease areas and help guide future clinical practice. METHODS: This cross-sectional study included adults with primary headache treated at 23 Chinese hospitals from September 2020 to May 2021. Fibromyalgia was diagnosed using the modified 2010 American College of Rheumatology criteria. Mood and insomnia were evaluated employing the Hospital Anxiety and Depression Scale and the Insomnia Severity Index. RESULTS: A total of 2782 participants were analyzed. The fibromyalgia prevalence was 6.0% (166/2782; 95% confidence interval: 5.1%, 6.8%). Compared to primary headache patients without combined fibromyalgia, patients with primary headache combined with fibromyalgia were more likely to be older (47.8 vs. 41.7 years), women (83.7% [139/166] vs. 72.8% [1904/2616]), less educated (65.1% [108/166] vs. 45.2% [1183/2616]), and with longer-duration headache (10.0 vs. 8.0 years). Such patients were more likely to exhibit comorbid depression (34.3% [57/166] vs. 9.9% [260/2616]), anxiety (16.3% [27/166] vs. 2.7% [70/2612]), and insomnia (58.4% [97/166] vs. 17.1% [447/2616]). Fibromyalgia was more prevalent in those with chronic (rather than episodic) migraine (11.1% [46/414] vs. 4.4% [72/1653], p < 0.001) and chronic (rather than episodic) tension-type headache (11.5% [27/235] vs. 4.6% [19/409], p = 0.001). Most fibromyalgia pain was in the shoulders, neck, and upper back. CONCLUSIONS: The prevalence of fibromyalgia in mainland Chinese patients with primary headache was 6.0%. Fibromyalgia was more common in those with chronic rather than episodic headache. The most common sites of fibromyalgia pain were the neck, shoulders, and back.

Dietary zinc intake and migraine in adults: a cross-sectional analysis of the National Health and Nutrition Examination Survey 1999-2004.

OBJECTIVE: The study examined the relationship between dietary zinc intake and migraine. BACKGROUND: Neuroinflammatory and oxidative stress are involved in the pathogenesis of migraine. Little is known about the effects of zinc, an anti-inflammatory and antioxidant trace element, on migraine. METHODS: The US National Health and Nutrition Examination Survey data from 1999 to 2004 were analyzed for this cross-sectional study. Participants who had severe headache or migraine were classified as having migraine. Dietary zinc intake was evaluated using the 24 h dietary recall system. RESULTS: A total of 11,088 participants were included, of whom, 20.2% (2236/11,088) reported having migraine disease. Compared to the lowest dietary zinc intake quintile (Q1, ≤5.9 mg/day), the adjusted odds ratios for migraine in Q2 (6.0-8.4 mg/day), Q3 (8.5-11.2 mg/day), Q4 (11.3-15.7 mg/day), and Q5 (≥15.8 mg/day) were 0.73 (95% confidence interval [CI]: 0.61-0.88, p = 0.004), 0.71 (95% CI: 0.56-0.91, p = 0.013), 0.71 (95% CI: 0.57-0.90, p = 0.008), and 0.70 (95% CI: 0.52-0.94, p = 0.029), respectively. Sensitivity analysis of zinc supplementation survey participants also showed an association between dietary zinc intake and migraine. Compared to the lowest total zinc intake quintile (Q1: 0.5-9.6 mg/day), the adjusted odds ratios for migraine in Q3 (19.3-24.3 mg/day) and Q4 (24.4-32.5 mg/day) were 0.62 (95% CI: 0.46-0.83, p = 0.019) and 0.67 (95% CI: 0.49-0.91, p = 0.045), respectively. CONCLUSIONS: Our findings indicate an inverse association between dietary zinc intake and migraine in adult Americans.

Similarities and differences between SUNCT and SUNA: a cross-sectional, multicentre study of 76 patients in China.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) have not been evaluated sufficiently due to limited data, particularly in China. METHODS: Patients with SUNCT or SUNA treated in a tertiary headache centre or seven other headache clinics of China between April 2009 and July 2022 were studied; we compared their demographics and clinical phenotypes. RESULTS: The 45 patients with SUNCT and 31 patients with SUNA had mean ages at onset of 37.22 ± 14.54 years and 42.45 ± 14.72 years, respectively. The mean ages at diagnosis of SUNCT and SUNA were 41.62 ± 12.70 years and 48.68 ± 13.80 years, respectively (p = 0.024). The correct diagnosis of SUNCT or SUNA was made after an average of 2.5 (0-20.5) years or 3.0 (0-20.7) years, respectively. Both diseases had a female predominance (SUNCT: 1.14:1; SUNA: 2.10:1). The two diseases differed in the most common attack site (temporal area in SUNCT, p = 0.017; parietal area in SUNA, p = 0.002). Qualitative descriptions of the attacks included stabbing pain (44.7%), electric-shock-like pain (36.8%), shooting pain (25.0%), and slashing pain (18.4%). Lacrimation was the most common autonomic symptom in both SUNCT and SUNA patients, while eyelid oedema, ptosis, and miosis were less frequent. Triggers such as cold air and face washing were shared by the two diseases, and they were consistently ipsilateral to the attack site. CONCLUSIONS: In contrast to Western countries, SUNCT and SUNA in China have a greater female predominance and an earlier onset. The shared core phenotype of SUNCT and SUNA, despite their partial differences, suggests that they are the same clinical entity.

Medication overuse headache associated with decreased dopamine transporter availability in the medial but not in the lateral orbitofrontal cortex: a 11CFT PET/MR study.

BACKGROUNDS: Dysfunction of the mesocorticolimbic dopamine system in medication overuse headache (MOH) is unknown. This study aimed to determine dopamine transporter (DAT) availability, which is sensitive to dopamine levels, in the mesocorticolimbic dopamine system in MOH patients. METHODS: This case-control study investigated eligible MOH patients admitted to the International Headache Centre in the neurological department of Chinese PLA General Hospital between July 2018 and August 2019. All subjects underwent an integrated positron emission tomography (PET)/magnetic resonance (MR) brain scans with 11CFT, a radioligand that binds to DAT. Standardised uptake value ratio (SUVr) images were compared voxelwise between MOH patients and healthy controls (HCs). SUVr values from significantly changed regions were extracted, and partial correlation analyses with clinical measures were conducted. RESULTS: We examined 17 MOH patients and 16 HCs. MOH patients had lower SUVr levels in the medial rather than lateral orbitofrontal cortex (OFC) than HCs (T = -5.0317, PGRF < 0.01), which showed no correlation with clinical features. CONCLUSIONS: MOH is characterised by decreased DAT availability in the medial OFC, which might reflect compensatory downregulation due to low dopamine signalling within the mesocorticolimbic dopamine system and provide a new perspective to understand the pathogenesis of MOH.

Association between Dietary Niacin Intake and Migraine among American Adults: National Health and Nutrition Examination Survey.

Migraine is related to brain energy deficiency. Niacin is a required coenzyme in mitochondrial energy metabolism. However, the relationship between dietary niacin and migraines remains uncertain. We aimed to evaluate the relationship between dietary niacin and migraine. This study used cross-sectional data from people over 20 years old who took part in the National Health and Nutrition Examination Survey between 1999 and 2004, collecting details on their severe headaches or migraines, dietary niacin intake, and several other essential variables. There were 10,246 participants, with 20.1% (2064/10,246) who experienced migraines. Compared with individuals with lower niacin consumption Q1 (≤12.3 mg/day), the adjusted OR values for dietary niacin intake and migraine in Q2 (12.4−18.3 mg/day), Q3 (18.4−26.2 mg/day), and Q4 (≥26.3 mg/day) were 0.83 (95% CI: 0.72−0.97, p = 0.019), 0.74 (95% CI: 0.63−0.87, p < 0.001), and 0.72 (95% CI: 0.58−0.88, p = 0.001), respectively. The association between dietary niacin intake and migraine exhibited an L-shaped curve (nonlinear, p = 0.011). The OR of developing migraine was 0.975 (95% CI: 0.956−0.994, p = 0.011) in participants with niacin intake < 21.0 mg/day. The link between dietary niacin intake and migraine in US adults is L-shaped, with an inflection point of roughly 21.0 mg/day.

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients.

BACKGROUND: There have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors. METHODS: The study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES. RESULTS: Among the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005). CONCLUSIONS: PAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.

Rates and Predictors of Relapse in Medication Overuse Headache: A Clinic-Based Study from China.

OBJECTIVE: This study aims to further assess the rates and risk factors for relapse in medication overuse headache (MOH) patients in China. METHODS: The patients were admitted to neurology outpatient clinics at Chinese PLA General Hospital (primarily for headache) and diagnosed with MOH. They responded well to 2 months of preventive treatment and completed a 1-year consultation. General information was collected, including demographic characteristics (age, height, weight, and education level), the clinical features of the headache and the use of pain relievers (type, frequency and duration). Differences in each factor between the group with relapse and the group without relapse were analyzed by the chi-square test or Wilcoxon test. Variables with a p < 0.05 were included as independent variables in nonconditional logistic regression analysis. RESULTS: In total, 129 patients were recruited for this retrospective study. The relapse rate of the MOH patients at the 1-year follow-up was 24.8%. The relapse rate was significantly higher in the patients with migraine (29/97, 29.9%) than in the patients with tension-type headache (3/32, 9.4%) and in the patients with low education levels (middle school or lower; 24/77, 31.6%) than in those with high education levels (high school or higher; 8/52, 15.4%). Nonconditional logistic regression analysis showed that the type of primary headache was an independent risk factor for MOH relapse (OR 3.719, p = 0.044). CONCLUSIONS: The relapse rate of MOH patients at the 1-year follow-up was 24.8% in China. The type of primary headache is an independent risk factor for MOH relapse, and patients with migraine as the primary headache are more prone to relapse.

A Chinese family with familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2.

BACKGROUND: ATP1A2 has been identified as the genetic cause of familial hemiplegic migraine type 2. Over 80 ATP1A2 mutations have been reported, but no data from Chinese family studies has been included. Here, we report the first familial hemiplegic migraine type 2 Chinese family with a novel missense mutation. METHODS: Clinical manifestations in the family were recorded. Blood samples from patients and the unaffected members were collected for whole-exome sequencing to identify the pathogenic mutation. Seven online softwares (SIFT, PolyPhen-2, PROVEAN, PANTHER, MutationTaster2, MutationAssessor and PMut) were used for predicting the pathogenic potential of the mutation. PredictProtein, Jpred 4 and PyMOL were used to analyze structural changes of the protein. The mutation function was further tested by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. RESULTS: All patients in the family had typical hemiplegic migraine attacks. Co-segregation of the mutation with the migraine phenotype in four generations, with 10 patients, was completed. The identified novel mutation, G762S in ATP1A2, exhibited the disease-causing feature by all the predictive softwares. The mutation impaired the local structure of the protein and decreased cell viability. CONCLUSION: G762S in ATP1A2 is a novel pathogenic mutation identified in a Chinese family with familial hemiplegic migraine, which causes loss of function by changing the protein structure of the Na+/K+-ATPase α2 subunit.

A case report of cough headache with transient elevation of intracranial pressure and bilateral internal jugular vein valve incompetence: A primary or secondary headache?

Background Primary cough headache (PCH) is precipitated by coughing or the Valsalva manoeuver (VM), and its underlying pathophysiology remains unclear. Case report We report a case of recurrent cough headaches precipitated by VM with transient increase of intracranial pressure (ICP) diagnosed by measuring left sigmoid sinus pressure. Bilateral internal jugular vein valve incompetence (IJVVI) was also diagnosed by Doppler ultrasonography during a VM. Indomethacin was administered for over four months, and the headache had completely disappeared at the four-month follow-up. Conclusions Cough headache might be associated with a transient increase of ICP induced by IJVVI, which might partially explain the pathophysiology of VM-induced headache. Detecting the internal jugular vein during a VM might be used as diagnostic procedure for patients who have PCH during resting and VM. If it is necessary, monitoring the ICP could be considered.

Laugh-Induced Headache: Clinical Features and Literature Review.

BACKGROUND: Laughing is a rare precipitating factor for headaches, and the pathogenesis underlying laugh-induced headache (LH) remains unclear. METHODS: Two cases of headache triggered predominantly by laughing were presented in this article. We also reviewed the published English literature regarding LH, summarized the clinical characteristics of LH, and discussed the probable pathophysiological mechanisms. RESULTS: In the first patient, magnetic resonance imaging of the brain revealed cerebellar tonsillar herniation through the foramen magnum. In the second patient, we did not find any evidence of intracranial disease. The literature review showed that LH is a mild to severe, non-pulsating headache. In most cases, the duration of each attack was limited to a few minutes. The headache usually bursts after laughing and reaches its peak almost immediately. In some cases, the headache can only be induced by mirthful laughing rather than by fake laughing. CONCLUSION: LH can be categorized as primary LH and secondary LH. Changes in the spatial structure in the posterior cranial fossa and cerebrospinal fluid circulation may contribute to the development of secondary LH. Primary LH, primary cough headache, and primary exercise headache may share some common pathogenesis. And we speculate that the regions of the brain associated with the expression of mirth might be associated with LH.