Ruozhuo Liu

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.

Abnormal Brain Functional Connectivity of the Hypothalamus in Cluster Headaches

The aim of this study was to detect the abnormality of the brain functional connectivity of the hypothalamus during acute spontaneous cluster headache (CH) attacks (‘in attack’) and headache-free intervals (‘out of attack’) using resting-state functional magnetic resonance imaging (RS-fMRI) technique. The RS-fMRI data from twelve male CH patients during ‘in attack’ and ‘out of attack’ periods and twelve age- and sex-matched normal controls were analyzed by the region-of-interest -based functional connectivity method using SPM5 software. Abnormal brain functional connectivity of the hypothalamus is present in CH, which is located mainly in the pain system during the spontaneous CH attacks. It extends beyond the pain system during CH attack intervals.

Application of ICHD-II Criteria in a Headache Clinic of China

Background China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese Peoples Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II). Methods and Results Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001). The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004). The peak age at onset of TTH for male and female were both in the 3rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2nd decade for females and the 1st decade for males. Conclusions/Significance This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria.

Validation of ICHD-3 beta diagnostic criteria for 13.7 Tolosa-Hunt syndrome: Analysis of 77 cases of painful ophthalmoplegia

Background Three editions of International Classification of Headache Disorders (ICHD) diagnostic criteria for Tolosa-Hunt syndrome (THS) have been published in 1998, 2004 and 2013; in ICHD-3 beta, there have been considerable changes. The validity of these new diagnostic criteria remains to be established. Methods We retrospectively identified 77 patients with non-traumatic painful ophthalmoplegia (PO) admitted between 2003 and 2013. We reviewed patients’ age at onset and gender, time courses between onset of pain and development of cranial nerve palsy, the cranial nerves involved, imaging findings, therapeutic efficacy of steroid treatment and recurrence of attacks. Results THS was the most frequent type of PO (46/77). In THS patients, the third cranial nerve was most commonly involved (76.3%). The median time interval between pain and cranial nerve palsy was two days, although in five patients (10.9%) the interval ranged from 16 to 30 days. Definitely abnormal MRI findings were found in 24 patients (52.2%). Conclusions It is essential to rule out other causes of PO in diagnosing THS, with MRI playing a crucial role in differential diagnosis. It may be helpful to understand and master the entity of THS for researchers and clinicians to adjust the gradation and ranking of the diagnostic criteria.

MTHFR C677T polymorphism and migraine risk: A meta-analysis

Many molecular epidemiological studies were carried out in recent years to assess the association between the MTHFR C677T polymorphism and migraine risk in diverse populations. However, the results remain controversial rather than conclusive. The objective of this study was to investigate the role of C677T MTHFR polymorphism in migraine pathogenesis. We performed a meta-analysis of published case-control studies concerning the association of the C677T MTHFR polymorphism and migraine. Pooled ORs were established using both random and fixed effects models. This meta-analysis on 17 studies with 8903 cases and 27,637 controls showed that the allele 677T was associated with a significantly increased risk of total migraine in Asians (TT vs. CT+CC: OR=1.62, 95% CI: 1.13-2.32, P(H)=0.573, I(2)=0.0%; T vs. C: OR=1.18, 95% CI: 1.00-1.40, P(H)=0.147, I(2)=44.1%). Similar results were also presented in Asian populations with MA (TT vs. CC: OR=1.62, 95% CI: 1.11-3.75; TT vs. CT+CC: OR=2.00, 95% CI: 1.01-3.95; T vs. C: OR=1.31, 95% CI: 1.02-1.69) without significant heterogeneity. We conclude that the C677T MTHFR polymorphism, responsible for a reduction of the MTHFR activity in folate metabolism, may act as a genetic susceptibility factor for migraine, MA in particular among the subjects of Asian descent.

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.

Factors that influence Tolosa-Hunt syndrome and the short-term response to steroid pulse treatment.

Some but not all patients with Tolosa-Hunt syndrome (THS) have dramatic responses to steroid treatment. A systematic study about the factors that may influence the steroid response of THS patients has not been published. We retrospectively identified 40 patients diagnosed with THS and treated with steroids with respect to patient age at onset, gender, the cranial nerve(s) involved, as well as imaging findings and laboratory tests. Within the context of these data we evaluated the therapeutic efficacy of steroid treatment and recurrence of attacks. We did not note a significant relationship between genders, whether THS was benign or inflammatory, the distribution of cranial nerve palsies, the initial dose of steroids and the effectiveness of steroid treatment for relief of orbital pain or cranial nerve palsies at 72 h or 1 week after treatment. Our study reveals that a rapid alleviation of pain by steroid treatment is a characteristic feature of THS patients. The alleviation of cranial nerve palsy is somewhat slower and more variable, and may involve additional mechanisms. There is an effect of patient age and whether attacks will recur (recurrence was more likely in patients who were young at the time of first attack), whether THS will be benign or inflammatory (more likely to be inflammatory in young patients) and the short-term response of cranial nerve palsy to steroid treatment, which was more effective in young patients. These relationships may be of value in counseling patients presenting with THS.

Medication-overuse headache in China: Clinical profile, and an evaluation of the ICHD-3 beta diagnostic criteria

Background Although medication-overuse headache (MOH) is common in China, its clinical profile is not yet fully established. Meanwhile, ICHD-3 beta has been published, but its diagnostic criteria require further validation. Methods We retrospectively classified the clinical features of 240 consecutive patients with MOH (55 males, 185 females), whose demographic data, headache features, overused medications (type, quantity, frequency and duration of use), headache-attributed burden, and outcomes were reviewed. We then applied the criteria of the several versions of ICHD (II, IIR and 3-beta) to these patients. Results Compared with those with other headaches, patients with MOH were more likely to be less well educated (64.6% vs 42.0% for secondary school or lower, p < 0.0001), and on lower annual incomes (72.3% vs 56.0% for an income of Chinese yuan (CNY) 30,000 or less, p < 0.0001). Combination analgesics were the most commonly overused medications, and, caffeine (89.9%), aminopyrine (70.0%), phenacetin (53.9%) and phenobarbital (48.8%) were the most commonly used specific components of these. Only two patients (0.8%) had previously been given the diagnosis of MOH; accordingly, the median time to diagnosis after the estimated onset of the disorder was 4.0 years. The majority of patients (83.7%) improved with treatment. All 240 patients fulfilled the diagnostic criteria for MOH according to ICHD-3 beta; only 134 (55.8%) satisfied the diagnostic criteria for definite MOH according to ICHD-II, while 195 (81.2%) met those of ICHD-IIR. Conclusions MOH in China is associated with lower educational level and annual income. MOH has rarely been diagnosed and correctly treated in China. ICHD-3 beta appears to be more appropriate for the diagnosis of MOH than previous versions.

Association between endothelial nitric oxide synthase gene polymorphism (T-786C) and ischemic stroke susceptibility: a meta-analysis

Background: The endothelial nitric oxide synthase (eNOS) T-786C polymorphism has been implicated in a number of studies investigating ischemic stroke (IS), yet previously published studies showed inconsistent results that recent meta-analyses have not resolved. Methods: In the comprehensive meta-analysis of 12 association studies involving 2836 IS cases and 3354 control subjects, we used a more stringent inclusion method and summarized data on the association of eNOS T-786C polymorphism and IS susceptibility. Results: We found a significantly lowered IS risk under the CC vs. TT genetic model (odds ratio, OR = 0.53, 95% confidence interval, CI = 0.29–0.98, p = 0.160, I2 = 45.5%) by random effects model in Caucasians and under the allele model C vs. T (OR = 0.42, 95% CI = 0.21–0.87) by fixed effects model in African-Americans. In addition, a significant increased risk of IS was observed in Asians (C vs. T: OR = 1.14, 95% CI = 1.02–1.28, p = 0.990, I2 = 0.0%) by fixed effects model. Stratified analysis by mean age also showed that the allele C carriers, compared with the allele T allele carriers, had higher risk of suffering IS (OR = 1.16, 95% CI = 1.03–1.31) in the population of 60–65 years without heterogeneity. Conclusions: The combined results suggest that eNOS T-786C polymorphism may be associated with IS susceptibility among the population between 60 and 65 years in particular.

Headache Care in China

Headache disorders are problematic worldwide. China is no different. A population‐based door‐to‐door survey revealed that the 1‐year prevalence of primary headache disorders in China was 23.8%, constituting a major societal burden. Many headache centers and clinics have been established in China, and headache disorders (and associated stress) are receiving an increased level of expert attention. This review summarizes the outcomes of the epidemiological survey and the progress of clinical and basic research in China, describes the present situation in terms of headache diagnosis and treatment, and discusses the future of headache care in China.