Aberrant modulations of static functional connectivity and dynamic functional network connectivity in chronic migraine.

BACKGROUND: Chronic migraine (CM) is a common and disabling neurological disorder that affects 1-2% of the global population. The aim of the present study was to identify the functional characteristics of the CM brain using static functional connectivity (s-FC), static functional network connectivity (s-FNC), and dynamic functional network connectivity (d-FNC) analyses. METHODS: In the present study, 17 CM patients and 20 sex- and age-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We utilized independent component (IC) analysis to identify 13 ICs. These 13 ICs were then classified into the following 6 resting-state networks (RSNs): the default mode network (DMN), executive control network (ECN), dorsal attention network, auditory network (AN), visual network (VN), and cerebellum network. Subsequently, s-FC, s-FNC, and d-FNC analyses of 13 ICs were employed for between-group comparisons. Three temporal metrics (fraction of time spent, mean dwell time, and number of transitions), which were derived from the state-transition vector, were calculated for group comparisons. In addition, correlation analyses were performed between these dynamic metrics and clinical characteristics [mean visual analog scale (VAS) scores, days with headache per month, days with migraine pain feature per month, and disease duration]. RESULTS: In the comparison of s-FC of 13 ICs within RSNs between the CM and HC groups, increased connectivity was observed in the left angular gyrus (Angular_L) of the ECN (IC 2) and the right superior parietal gyrus (Parietal_Sup_R) of the AN (IC 5), and reduced connectivity was found in the left superior frontal gyrus (Frontal_Sup_2_L) of the AN (IC 5) and DMN (IC 19), the right calcarine sulcus (Calcarine_R) of the VN (IC 7), and the left precuneus (Precuneus_L) of the DMN (IC 17) in CM patients. In the comparison of the d-FNC of 13 IC pairs within RSNs between the two groups, the CM group exhibited significantly decreased connections between the DMN (IC 11) and AN (IC 5), and increased connections between the ECN (IC 2, IC 4) and DMN (IC 19), ECN (IC 4) and AN (IC 5), and ECN (IC 4) and VN (IC 13) in state 1. However, no significant differences in s-FNC were observed between the two groups during the s-FNC analysis. Between-group comparisons of three dynamic metrics between the CM and HC groups showed a longer fraction of time spent and mean dwell time in state 2 for CM patients. Furthermore, from the correlation analyses between these metrics and clinical characteristics, we observed a significant positive correlation between the number of transitions and mean VAS scores. CONCLUSIONS: Our findings suggest that functional features of the CM brain may fluctuate over time instead of remaining static, and provide further evidence that migraine chronification may be related to abnormal pattern connectivity between sensory and cognitive brain networks.

Isaacs syndrome with CASPR2 antibody: A series of three cases.

Isaacs syndrome is a form of peripheral nerve hyperexcitability, characterized by spontaneous muscle twitching and stiffness. Some patients are reported to be positive for CASPR2 antibody that may be one of the pathogenic autoantibodies in Isaacs syndrome. We reported a series of three patients with Isaacs syndrome, including their clinical features, electrophysiologic findings, laboratory parameters and therapeutic responses. All the three patients were positive for CASPR2 antibodies examined on transfected human embryonic kidney 293 cells by indirect immunofluorescence method. One patient had invasive thymoma. Symptomatic treatment was not sufficient for them, while immunotherapies including corticosteroids, double filtration plasmapheresis and rituximab provided favorable outcomes. The titers of CASPR2 antibody decreased after immune modulating therapy in parallel to clinical improvements in two patients.

Familial occurrence of headache disorders: A population-based study in mainland China.

BACKGROUND: Headache disorders are highly prevalent worldwide, and familial occurrence and heredity are contributory factors attracting the interest of epidemiological researchers. Our purpose, in a large sample drawn nationwide from the Chinese general population, was to evaluate the frequency of similar headache in first-degree relatives (FDRs) of those with different headache types. METHODS: This was a questionnaire-based nationwide cross-sectional door-to-door survey using cluster random-sampling, selecting one adult (18-65 years) per household. Headache was diagnosed by ICHD-II criteria. Participants with headache were asked whether or not any FDRs had similar headache to their own. Chi-squared test and multivariate logistic regression analysis were used to assess the strength and significance of associations. RESULTS: Of 5041 survey participants (participation rate 94.1%), 1060 (21.0%) were diagnosed with headache (migraine 469 [9.3%], tension-type headache [TTH] 543 [10.8%], headache on ≥15 days/month 48 [0.95%]). From these, 31 were excluded because of missing data about FDRs, leaving 1029 for analysis (male 350 [mean age: 46.7±11.4years]; female 679 [mean age 46.3±11.2years]). Similar headache in one or more FDRs was reported by 22.2% (95% CI: 19.6-24.7%) overall, by 25.1% (21.1-29.1%) of those with migraine, by 19.1% (15.7-22.4%) with TTH and by 29.2% (16.3-42.0%) with headache on ≥15 days/month. The differences was significant between migraine and TTH (OR=1.4, p=0.023), but were not significant between headache on ≥15 days/month and TTH (OR=1.7, p=0.093), migraine and headache on ≥15 days/month (OR=1.2,p=0.534). In multivariate analysis: for migraine versus TTH,AOR=1.2 (p=0.015); for headache on ≥15 days/month versus TTH, AOR 2.3 (p=0.018). CONCLUSION: Headache was highly prevalent in China and common among FDRs of those with any type of headache (headache on ≥15 days/month>migraine>TTH). Against the background of the general-population prevalence of each disorder, familial occurrence was a very highly influential factor in headache on ≥15 days/month. There are important implications in this for public health and education.

Elevated blood pressure and headache disorders in China--associations, under-treatment and implications for public health.

BACKGROUND: Both hypertension (HTN) and headache disorders are highly prevalent worldwide. Our purpose, in a nationwide study of the Chinese general population, was to evaluate any association between primary headache disorders and elevated blood pressure (eBP). We could not collect data on antihypertensive therapy, but took the view that, whatever such therapy might be taken, eBP was a sign that it was failing to meet treatment needs. Therefore, as a secondary purpose, important from the public-health perspective, we would present the prevalence of eBP (treated or not) as indicative of unmet health-care need in China. METHODS: This was a questionnaire-based nationwide cross-sectional door-to-door survey using cluster random-sampling, selecting one adult (18-65 years) per household. Headache was diagnosed by ICHD-II criteria and eBP as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Chi-squared test and multivariate logistic regression analysis were used to assess the strength and significance of associations. We set significance at P ≤ 0.05. RESULTS: Of 5,041 survey participants (participation rate 94.1 %), 154 were excluded because of missing BP data, leaving 4,987 for analysis [mean age: 43.6 ± 12.8 years; male 2,532 (mean age: 43.4 ± 12.9 years); female 2,455 (mean age 43.9 ± 12.8 years)]. There were 466 participants with migraine, 535 with tension type headache (TTH) and 48 with all causes of headache on ≥15 days/month. The prevalence of eBP was 22.1 % (males 22.9 %, females 21.3 %). No associations of eBP with any of the headache disorders survived multivariate adjusted analysis. The demographic and anthropometric variables most strongly associated with eBP were higher age (AOR 3.7) and being overweight (AOR 2.4), seen in both genders. Less strong were male gender, lower educational level and urban habitation. CONCLUSIONS: We found no clear-cut associations between eBP and any headache disorder. The associations with demographic and anthropometric variables may have acted as confounders in past reports to the contrary. We did find an alarmingly high prevalence of eBP, recognizing that this signals substantial under-treatment in China of a serious condition, and therefore a major public-health concern.

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Duliang Soft Capsule in Patients with Chronic Daily Headache.

Objective. To investigate the efficacy and safety of traditional Chinese medicine Duliang soft capsule (DSC) in prophylactic treatment for patients with chronic daily headache (CDH). Methods. A multicenter, double-blind, randomized, placebo-controlled clinical study was conducted at 18 Chinese clinical centers. The participants received either DSC or placebo for 4 weeks. The primary efficacy measure was headache-free rate (HFR) in a 4-week period between the pretreatment and posttreatment stages. The secondary efficacy measures were the decrease of headache days, the duration of headache attacks, the frequency of analgesic usage, quality of life, disability, and the headache severity (VAS scores). The accompanying symptoms and adverse events were also assessed. Results. Of 584 CDH patients assessed, 468 eligible patients were randomized. 338 patients received DSC, while 111 patients were assigned in the placebo group. Following treatment, there was a 16.56% difference in HFR favoring DSC over placebo (P < 0.01). Significant differences were also observed between DSC and placebo groups in the secondary measures. However, no statistical difference was found between the two groups in the associated symptoms. No severe adverse effects were observed in the study. Conclusions. DSC might be an effective and well-tolerated option for the prophylactic treatment of patients with CDH.

Health-care utilization for primary headache disorders in China: a population-based door-to-door survey.

BACKGROUND: In order to know the status quo of health care for primary headache disorders in China, questions about headache consultation and diagnosis were included in a nationwide population-based survey initiated by Lifting The Burden: the Global Campaign against Headache. METHODS: Throughout China, 5,041 unrelated respondents aged 18-65 years were randomly sampled from the general population and visited unannounced at their homes. After basic sociodemographic and headache diagnostic questions, respondents with headache answered further questions about health-care utilization in the previous year. RESULTS: Significantly higher proportions of respondents with migraine (239/452; 52.9%) or headache on ≥15 days per month (23/48; 47.9%) had consulted a physician for headache than of those with tension-type headache (TTH) (218/531; 41.1%; P < 0.05). Multivariate analysis showed associations between disability and probability of consultation in those with migraine (mild vs. minimal: AOR 3.4, 95% CI: 1.6-7.4; moderate vs. minimal: 2.5, 1.2-5.4; severe vs. minimal: 3.9, 1.9-8.1) and between rural habitation and probability of consulting in those with TTH (AOR: 3.5; 95% CI: 1.9-6.3, P < 0.001). Married respondents with TTH were less likely than unmarried to have consulted (AOR: 0.26; 95% CI: 0.07-0.93; P = 0.038). About half of consultations (47.8-56.5%) for each of the headache disorders were at clinic level in the health system. Consultations in level-3 hospitals were relatively few for migraine (5.9%) but more likely for headache on ≥15 days/month (8.7%) and, surprisingly, for TTH (13.3%). Under-diagnosis and misdiagnosis were common in consulters. More than half with migraine (52.7%) or headache on ≥15 days/month (51.2%), and almost two thirds (63.7%) with TTH, reported no previous diagnosis. Consulters with migraine were as likely (13.8%) to have been diagnosed with "nervous headache" as with migraine. "Nervous headache" (9.8%) and "vascular headache" (7.6%) were the most likely diagnoses in those with TTH, of whom only 5.6% had previously been correctly diagnosed. These were also the most likely diagnoses (14.0% each) in consulters with headache on ≥15 days/month. CONCLUSIONS: This picture of the status quo shows limited reach of headache services in China, and high rates of under-diagnosis and misdiagnosis in those who achieve access to them. This is not a picture of an efficient or cost-effective response to major causes of public ill-health and disability.

Headache yesterday in China: a new approach to estimating the burden of headache, applied in a general-population survey in China.

BACKGROUND: In order to minimize recall bias in burden estimation, questions about headache yesterday were included in a population-based survey initiated by LIFTING THE BURDEN : The Global Campaign against Headache. METHODS: Throughout China, nonrelated respondents aged 18-65 years were randomly sampled from the general population by a door-to-door survey. A validated structured questionnaire included inquiry into occurrence and burden of headache on the preceding day ("headache yesterday"). RESULTS: The participation rate was 94.1%. Of 5041 participants, 286 (5.7%) (male 3.6%, female 7.9%) reported headache yesterday. Age-weighted prevalence of headache yesterday was 4.8% (male 3.0%, female 6.6%). Headache yesterday lasted all day in 36.8%, <1 hour in 14.3% and for a mean of 3.7 ± 3.3 hours in 48.9%. Headache yesterday was moderate to severe in 79.9%; disability such that they could do less than half of what they had expected was reported by 19.9% and such that they could do nothing by a further 7.5% (total 27.4%). Almost three-quarters (71.5%) with headache yesterday took medication to treat it. CONCLUSIONS: Of the adult Chinese population, 1.8% have headache at any one time that is of moderate to severe intensity in 1.4%, and 1.3% lose the equivalent of a whole day to headache-attributed disability every day. In China this means 12.3 million people.

Body mass index and migraine: a survey of the Chinese adult population.

The objective of this study is to evaluate the association between body mass index (BMI) and migraine in general population Chinese cohort. This was a cross-sectional secondary analysis from a general population Chinese cohort of men and women of reproductive and post-reproductive age ranging between 18 and 65 years. Migraine was defined utilizing ICHD criteria. Body mass indices were calculated using measured height and weight and categorized based on the World Health Organizations criteria. The 1-year period prevalence of migraine was 9.3 %. No association was identified between migraine and those with a BMI < 30.0. Compared to those with normal BMI (18.5-23.0), those with BMI ≥ 30 (morbid obesity) had a greater prevalence of migraine (8.6 vs. 13.8 %, p = 0.000). Multivariate-adjusted odds ratio demonstrated that those with morbid obesity had a greater than twofold increased odds of migraine [OR 2.10 (1.39-3.12)] as compared to those with a BMI between 18.5 and 23.0. No association was found between obesity and migraine severity, frequency, or disability. Morbid obesity was associated with twofold increased odds of migraine in this Chinese men and women cohort of predominantly reproductive age.

The prevalence and burden of primary headaches in China: a population-based door-to-door survey.

OBJECTIVES: In the absence of reliable data on the prevalence and burden of primary headache disorders in the mainland of China, a population-based survey was initiated by Lifting The Burden: the Global Campaign against Headache. METHODS: Throughout all regions of China, 5041 non-related adult respondents aged 18-65 years were randomly sampled from the general population according to the expanded programme on immunization method established by World Health Organization. They were visited by door-to-door calling and surveyed using the structured questionnaire developed by Lifting The Burden, translated into Chinese and adapted to Chinese culture after a pilot study. RESULTS: The responder rate was 94.1%.The estimated 1-year prevalence of primary headache disorders was 23.8% (95%confidence interval 22.6-25.0%), of migraine 9.3% (95% confidence interval 8.5-10.1%), of tension-type headache (TTH) 10.8%(9.9-11.6%), and of chronic daily headache (CDH) 1.0% (0.7-1.2%). Of respondents with migraine, TTH, and CDH, moderate or severe impact and therefore high need for effective medical care were reported by 38.0%, 23.1%, and 47.9%, respectively.The World Health Organization quality of life-8 questionnaire showed that all 3 types of headache reduced life quality. The total estimated annual cost of primary headache disorders, including migraine,TTH, and CDH was CNY 672.7 billion, accounting for 2.24% of gross domestic product (GDP) (direct cost: CNY 108.8 billion, 0.36% of GDP; indirect cost: CNY 563.9 billion, 1.88%of GDP). CONCLUSION: The prevalence of primary headaches is high in China and not dissimilar from the world average. These headaches cause disability, impair work, study and daily activities, decrease life quality, and bring about a heavy and hitherto unrecognized socioeconomic burden.

The burden of headache in China: validation of diagnostic questionnaire for a population-based survey.

The objective of this study was to test the validity, in the Chinese population, of the Lifting The Burden diagnostic questionnaire for the purpose of a population-based survey of the burden of headache in China. From all regions of China, a population-based sample of 417 respondents had completed the structured questionnaire in a door-to-door survey conducted by neurologists from local hospitals calling unannounced. They were contacted for re-interview by telephone by headache specialists who were unaware of the questionnaire diagnoses. A screening question ascertained whether headache had occurred in the last year. If they had, the specialists applied their expertise and ICHD-II diagnostic criteria to make independent diagnoses which, as the gold standard, were later compared with the questionnaire diagnoses. There were 18 refusals; 399 interviews were conducted in 202 women and 197 men aged 18-65 years (mean age 44.4±12.6 years). In comparison to the specialists' diagnoses, the sensitivity, specificity, positive predictive value, negative predictive value and Cohen's kappa (95% CI) of the questionnaire for the diagnosis of migraine were 0.83, 0.99, 0.83, 0.99 and 0.82 (0.71-0.93), respectively; for the diagnosis of tension-type headache (TTH), they were 0.51, 0.99, 0.86, 0.92 and 0.59 (0.46-0.72), respectively. In conclusion, the questionnaire was accurate and reliable in diagnosing migraine (agreement level excellent), less so, but adequate, for TTH (sensitivity relatively low, false negative rate relatively high and agreement level fair to good). The non-specific features of TTH do not lend themselves well to diagnosis by questionnaire.

Report on the first Chinese family with Gerstmann-Sträussler-Scheinker disease manifesting the codon 102 mutation in the prion protein gene.

The authors found a female patient aged 33-years with dementia and cerebellar ataxia rapidly progressing for a year. EEG tracings were abnormal but without features of typical CJD. The patient died 13 months after the onset of illness. Biopsy of her cerebral cortex showed moderate spongiform changes, neuronal loss and gliosis. Numerous deposits of eosinophilic substance amorphous or in the shape of Kuru plaques were disclosed in the cerebral cortex. All deposits stained strongly with monoclonal 3F4 antibody to human prion protein. Genetic studies disclosed the Pro to Leu point mutation at codon 102 with a 102 Leu-129 Met in the PrP gene. Codon 129 was heterozygous for Met/Val, and codon 219 was homozygous for Glu/Glu. It was established; moreover, that the patient's grandfather had a similar disease and died at age 48 and the patient's brother died after a 10-year long neurological disease diagnosed as hereditary cerebellar ataxia. On the basis of clinical, neuropathological and genetic findings, the authors diagnosed the Gerstmann-Sträussler-Scheinker disease, a familial prion disease with an autosomal dominant character. This is the first report on this disease in China.