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.

Migraine-like headache in subjects with isolated Lambl's excrescences: a case series and literature review.

AIM: Lambl's excrescences are mobile, thin, fibrinous connective tissue strands typically found on left-sided cardiac values. Migraine is positively associated with structural cardiac anomalies. However, it remains unclear whether Lambl's excrescences are associated with migraine. METHODS: Retrospective review of 182 inpatients with Lambl's excrescences confirmed by transesophageal echocardiogram in Chinese PLA General Hospital since January 2010. Among them, those with isolated Lambl's excrescences presented with migraine-like headache were included. We collected information on the demographics and clinical profiles of all participants, and performed follow-up visits. RESULTS: A total of 8 patients presented with migraine-like headache among 15 patients with isolated Lambl's excrescences. They included 2 men and 6 women, with an average age of 44.63 ± 12.24 years. Among these patients, 3 had visual aura, and 6 manifested infarct-like lesions on magnetic resonance imaging, of which 2 developed lesions after first visit. During follow-up, 4 patients suffering from intervention for Lambl's excrescences dramatically reduced headache recurrence compared to the other 4 patients only receiving migraine preventive medications. CONCLUSIONS: This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache. And intervention for Lambl's excrescences may be crucial for preventing headache recurrence.

This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache.The small sample size study fails to make management recommendations.

AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization.

BACKGROUND: Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM. METHODS: Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention. RESULTS: Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1ß, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway. CONCLUSIONS: AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.

Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats.

BACKGROUND: Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood. METHODS: The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats. RESULTS: The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application. CONCLUSIONS: Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.

Acute sleep deprivation aggravates nitroglycerin-evoked hyperalgesia in mice.

Sleep deprivation can trigger migraine, and migraineurs often choose to sleep to relieve headaches during acute migraine. This study aimed to explore the effect of acute sleep deprivation on hyperalgesia induced by nitroglycerin in mice. In part one, after either 6-h sleep deprivation or 6-h normal sleep, mice were intraperitoneally injected with nitroglycerin or saline. The mechanical pain threshold and withdrawal latency of the hindpaw were measured every 30 min for 6 h. Next, the same sleep deprivation and injection procedure was performed with new mice, and mice were sacrificed 4.5 h after injection. The trigeminal nucleus caudalis and upper cervical spinal segments were taken for immunofluorescence Fos staining. In part two, after injection of saline or nitroglycerin, the mice were either deprived of sleep for 6 h or allowed to sleep without interference. The mechanical and thermal pain threshold were measured after 6 h. In part three, we compared the sleep time of mice after intraperitoneal injection of saline or nitroglycerin without interference. Sleep deprivation for 6 h did not cause any changes in the baseline pain thresholds in mice. However, pretreatment with 6-h sleep deprivation significantly prolonged the duration of hyperalgesia induced by nitroglycerin. Additionally, the expression of Fos at 4.5 h was significantly higher in the 6-h sleep deprivation and nitroglycerin group than in the other three groups. When intraperitoneal injection was given first, the mechanical pain threshold of the hind paw was significantly lower in the group that received nitroglycerin with 6-h sleep deprivation than in the other groups. Compared to the saline injection, one-time nitroglycerin injection would result in a significant increase in sleep latency and decrease in sleep duration for the normal mice. Acute sleep deprivation significantly aggravated the hyperalgesia induced by nitroglycerin in mice, which highlights the importance of sleep disorders for migraine.

The applicability research of the diagnostic criteria for 10.2 Heamodialysis-related headache in the international classification of headache disorders-3rd edition.

BACKGROUND: Headache during hemodialysis (HDH) is prevalent but not negligible. Despite the high prevalence of dialysis headaches, they have rarely been studied. Therefore, this study aimed to evaluate the prevalence, risk factors, and clinical characteristics of HDH and reappraise the HDH diagnostic criteria in the International Classification of Headache Disorders 3 (ICHD-3). METHODS: One hundred and fifty-four patients completed this randomized cross-sectional study. Consecutive patients who underwent haemodialysis were assessed using a semi-structured questionnaire. The patients were administered face-to-face questionnaires while undergoing dialysis. RESULTS: This study included 154 patients. Before commencing dialysis, 3.24% (5/154) of the patients had migraine without aura, 1.29% (2/154) had menstrual-related migraine, 0.6% (1/154) had tension-type headaches, and 0.6% (1/154) had an unclassifiable headache. One case (0.6%) of headache resolved after dialysis treatment. HDH was diagnosed in 9.09% (14/154) of the patients. Headache after haemodialysis (HAH) was reported in 6.49% (10/154) of patients. The most prevalent features of HDH were frontal or temporal location, bilateral headaches, dull and throbbing nature, and moderate severity. HDH started at a mean of 2.33 ± 0.79 h after dialysis commenced. The average headache duration was 6.56 ± 1.57 h (median = 3.0 h), with 66.67% of the patients reporting a duration of ≤4 h. HDH was more prevalent in females than males (P = 0.01, P < 0.05). Female sex was a risk factor for HDH (P = 0.01，P < 0.05). CONCLUSIONS: The diagnostic criteria for 10.2 HDH in ICHD-3 may miss several HAH. Therefore, ICHD-3 should be revised according to the literature and further studies.

Characteristics of headache during and/or after coronary intervention: A prospective observational study.

INTRODUCTION: Headache during and/or after coronary intervention is common but has received little attention from cardiologists and neurologists. The purpose of this study was to investigate the incidence, risk factors, and possible mechanism of coronary intervention-related headache. METHODS: Using a prospective observational design, we identified consecutive patients with coronary intervention from May 2020 to August 2020. Patients were followed up with questionnaires immediately after coronary intervention and 24 h, 72 h, 1 week and 2 weeks after the intervention. RESULTS: In total, 94 patients were enrolled, and 71 patients ultimately completed the 2-week follow-up. Among 71 patients, headache developed during and/or after coronary intervention in 18 (25.4%) patients. Two different types of headache related to coronary intervention were observed: One during and another after coronary intervention. Headache characteristics are described in detail. A history of previous headache was an independent risk factor for coronary intervention-related headache (p < 0.01). CONCLUSIONS: Coronary intervention-related headache has an incidence of 25.4%, and previous headache history was an independent risk factor. Moreover, considering that there are no relevant diagnostic criteria, it is suggested that the definition of coronary intervention-related headache should be established in the International Classification of Headache Disorders.

Temporal characteristics of astrocytic activation in the TNC in a mice model of pain induced by recurrent dural infusion of inflammatory soup.

BACKGROUND: Astrocytic activation might play a significant role in the central sensitization of chronic migraine (CM). However, the temporal characteristics of the astrocytic activation in the trigeminal nucleus caudalis (TNC) and the molecular mechanism under the process remain not fully understood. Therefore, this study aims to investigate the duration and levels change of astrocytic activation and to explore the correlation between astrocytic activation and the levels change of cytokines release. METHODS: We used a mice model induced by recurrent dural infusion of inflammatory soup (IS). The variation with time of IS-induced mechanical thresholds in the periorbital and hind paw plantar regions were evaluated using the von Frey filaments test. We detected the expression profile of glial fibrillary acidic protein (GFAP) in the TNC through immunofluorescence staining and western blot assay. We also investigated the variation with time of the transcriptional levels of GFAP and ionized calcium binding adapter molecule 1 (Iba1) through RNAscope in situ hybridization analysis. Then, we detected the variation with time of cytokines levels in the TNC tissue extraction and serum, including c-c motif chemokine ligand 2 (CCL2), c-c motif chemokine ligand 5 (CCL5), c-c motif chemokine ligand 7 (CCL7), c-c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 1 (CXCL1), c-x-c motif chemokine ligand 13 (CXCL13), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), macrophage colony-stimulating factor (M-CSF), interleukin 1beta (IL-1ß), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17A (IL-17A). RESULTS: Recurrent IS infusion resulted in cutaneous allodynia in both the periorbital region and hind paw plantar, ranging from 5 d (after the second IS infusion) to 47 d (28 d after the last infusion) and 5 d to 26 d (7 d after the last infusion), respectively. The protein levels of GFAP and messenger ribonucleic acid (mRNA) levels of GFAP and Iba1 significantly increased and sustained from 20 d to 47 d (1 d to 28 d after the last infusion), which was associated with the temporal characteristics of astrocytic activation in the TNC. The CCL7 levels in the TNC decreased from 20 d to 47 d. But the CCL7 levels in serum only decreased on 20 d (1 d after the last infusion). The CCL12 levels in the TNC decreased on 22 d (3 d after the last infusion) and 33 d (14 d after the last infusion). In serum, the CCL12 levels only decreased on 22 d. The IL-10 levels in the TNC increased on 20 d. CONCLUSIONS: Our results indicate that the astrocytic activation generated and sustained in the IS-induced mice model from 1 d to 28 d after the last infusion and may contribute to the pathology through modulating CCL7, CCL12, and IL-10 release.

The applicability research of the diagnostic criteria for 6.7.2 angiography headache in the international classification of headache disorders-3rd edition.

BACKGROUND: Angiography headache (AH) is common but not negligible, and the criteria for AH have been based on only a few studies. The purpose of this study was to investigate the incidence, risk factors and possible mechanism of AH and reappraise the diagnostic criteria for AH in the International Classification of Headache Disorders 3 (ICHD-3). METHODS: Two hundred and seventy-nine patients completed this prospective, non-randomized study, including 107 patients who underwent cerebral angiography, 101 patients who underwent coronary intervention and 71 patients who underwent extremities arterial intervention. Patients were followed up with questionnaires immediately after the procedure and 24 h, 72 h, 1 week and 2 weeks after the procedure. RESULTS: The incidence of headache was 22.4% (24/107) in cerebral angiography group, 23.8% (24/101) in coronary intervention group, and 16.9% (12/71) in extremities arterial intervention group. Headache still occurred in 12.1% (13/107), 14.9% (15/101) and 11.3% (8/71) of patients 24 h after the procedure in the three groups, respectively. Two types of headache were observed in cerebral angiography group and coronary intervention group, one during and one after the procedure, while only postoperative headache was observed in extremities arterial intervention group. Previous headache history was a risk factor for headache in the three groups (p = 0.003 in cerebral angiography group, p = 0.006 in coronary intervention group, and p = 0.016 in extremities arterial intervention group). In addition, female (p = 0.008) was a risk factor for cerebral angiography group. Headache characteristics were described in detail. CONCLUSIONS: The diagnostic criteria for 6.7.2 angiography headache in ICHD-3 may miss a number of cerebral AH with onset later than 24 h after the procedure. Therefore, it is recommended to revise it according to the literature and further studies. The incidence of headache was high during and after angiography and interventional procedure. It was suggested that the definition of headache due to coronary intervention and headache due to extremities arterial intervention should be added in ICHD.

Functional correlation of ATP1A2 mutations with phenotypic spectrum: from pure hemiplegic migraine to its variant forms.

BACKGROUND: Mutations in ATP1A2, the gene encoding the α2 subunit of Na+/K+-ATPase, are the main cause of familial hemiplegic migraine type 2 (FHM2). The clinical presentation of FHM2 with mutations in the same gene varies from pure FHM to severe forms with epilepsy and intellectual disability, but the correlation of these symptoms with different ATP1A2 mutations is still unclear. METHODS: Ten ATP1A2 missense mutations were selected according to different phenotypes of FHM patients. They caused pure FHM (FHM: R65W, R202Q, R593W, G762S), FHM with epilepsy (FHME: R548C, E825K, R938P), or FHM with epilepsy and intellectual disability (FHMEI: T378N, G615R, D718N). After ouabain resistance and fluorescence modification, plasmids carrying those mutations were transiently transfected into HEK293T and HeLa cells. The biochemical functions were studied including cell survival assays, membrane protein extraction, western blotting, and Na+/K+-ATPase activity tests. The electrophysiological functions of G762S, R938P, and G615R mutations were investigated in HEK293T cells using whole-cell patch-clamp. Homology modeling was performed to determine the locational distribution of ATP1A2 mutations. RESULTS: Compared with wild-type pumps, all mutations showed a similar level of protein expression and decreased cell viability in the presence of 1 µM ouabain, and there was no significant difference among the mutant groups. The changes in Na+/K+-ATPase activity were correlated with the severity of FHM phenotypes. In the presence of 100 µM ouabain, the Na+/K+-ATPase activity was FHM > FHME > FHMEI. The ouabain-sensitive Na+/K+-ATPase activity of each mutant was significantly lower than that of the wild-type protein, and there was no significant difference among all mutant groups. Whole-cell voltage-clamp recordings in HEK293T cells showed that the ouabain-sensitive pump currents of G615R were significantly reduced, while those of G762S and R938P were comparable to those of the wild-type strain. CONCLUSIONS: ATP1A2 mutations cause phenotypes ranging from pure FHM to FHM with epilepsy and intellectual disability due to varying degrees of deficits in biochemical and electrophysiological properties of Na+/K+-ATPase. Mutations associated with intellectual disability presented with severe impairment of Na+/K+-ATPase. Whether epilepsy is accompanied, or the type of epilepsy did not seem to affect the degree of impairment of pump function.

Prevalence and risk factors associated with headache amongst medical staff in South China.

BACKGROUND: A previous study by our team reported the prevalence of primary headache disorders and factors associated with headache among nurses in three hospitals in North China. The aim of this cross-sectional survey was to learn more about how medical nurses in South China were affected by headache. Additionally, we determined the prevalence of headache and measured the impact of headache among doctors in mainland China for the first time. METHODS: Stratified random cluster sampling was used to select 280 physicians and 365 nurses from various departments in four hospitals in Sanya, which is one of southernmost cities in China. Information was collected on demographic data, occupational factors and headache characteristics by using a structured questionnaire. RESULTS: Among 645 medical staff, 548 (85%) responded (doctors = 240, nurses = 308). Among the medical staff, the 1-year prevalence of primary headache disorders was 50%, with 25.9% experiencing migraine and 24.1% experiencing tension-type headache (TTH). The prevalence of migraine in female doctors was higher than that in female nurses, although this difference was not significant (32.4% vs. 29.8%, P = 0.628). Multivariate analysis showed that being female and working in other specialties (Emergency Department & Radiology Department) remained independent risk factors for migraine in doctors (OR 2.314 and 3.223). In nurses, being married was a risk factor for migraine (OR 3.728), and job titles remained an independent risk factor for migraine and TTH (OR 2.294 and 4.695). Working more than 6 night-shifts per month was associated with an increased prevalence of migraine and TTH in doctors; the same was true in nurses for migraine, but not for TTH. CONCLUSION: The prevalence of primary headache disorders in both nurses and doctors is higher than that in the general population in South China. Our study shows that occupation, geography and sex may play an important role. Further, female doctors are more susceptible than female nurses to migraine. The risk factors relevant to headache that were found in this study should provide an important reference for promoting occupational health in medical staff, especially female doctors in China.

Headache attributed to cranial venous sinus stenting: A case series and literature review.

BACKGROUND: The diagnostic criteria for headache attributable to cranial venous sinus stenting were first formalized in the recently published third edition of the International Classification of Headache Disorders (ICHD-3). However, the diagnostic criteria for headache caused by cranial venous sinus stenting are based on very few data and the condition is poorly characterized. OBJECTIVES: To validate the diagnostic criteria for cranial venous sinus stenting headache by retrospectively studying the characteristics of headache in patients with isolated pulsatile tinnitus who underwent curative cranial venous sinus stenting and who had not previously complained of headache. PATIENTS AND METHODS: We retrospectively studied clinical, radiological, and manometric data from patients with isolated venous pulsatile tinnitus who had not previously reported headache. All patients underwent lateral sinus stenting in our institution between October 2010 and February 2018. RESULTS: Forty eight patients, 47 females and one male, were enrolled. The mean age at symptom onset was 36.2 ± 8.7 years and the mean body mass index was 24.0 ± 3.2 kg/m2. Lateral sinus stenosis was evident in 47 patients and a sigmoid diverticulum in one. Fourteen patients experienced headaches after recovering from general anesthesia. All were female, with a mean age of 35.5 ± 9.6 years. Headache persisted for less than 3 days in six patients (42.8%); for 3 days to 3 months in four (28.6%); and for longer than 3 months in four (28.6%). The headaches were located on the same sides as the cranial venous sinus stents in 13 patients (92.9%) and were principally occipital, being oppressive in nine patients (64.3%) and of moderate intensity in seven (50%). Age at onset of pulsatile tinnitus and body mass index were significantly associated with headache (p < 0.05; t-test). CONCLUSION: To the best of our knowledge, this is the first study to describe cranial venous sinus stenting headache in detail. We found that de novo headache developed after cranial venous sinus stenting, and was usually mild to moderate, unilateral, but oppressive; almost one-third of such headaches persisted for more than 3 months. Researchers and clinicians must become familiar with this headache spectrum; further prospective studies are required.

Unnecessary Neuroimaging for Patients With Primary Headaches.

Background - Headache may be due to either a primary or secondary disorder, and neuroimaging assessments can play an important role when differentiating between these types of headache. Although many studies have reported no significant differences between primary headache patients and the general population in terms of abnormal neuroimaging findings, others have shown that neuroimaging may be employed to rule out secondary causes of headache that could impact morbidity and mortality. This issue remains under debate. Thus, the present study compared the neuroimaging findings of headache patients and healthy controls. Methods - This study recruited 1070 healthy controls and 1070 primary headache patients from the Chinese People's Liberation Army General Hospital. The primary headache patients were diagnosed by computerized clinical decision support systems, and re-diagnosed by a specialist. All participants were assessed with either computed tomography or magnetic resonance imaging (MRI) scans. The neuroimaging findings were classified as significant abnormalities, non-significant abnormalities, or normal. Results - All the significant abnormalities were found using MRI scans. Significant abnormalities were identified in 4 primary headache patients (0.58%) and 5 healthy controls (0.73%); the rate of significant abnormalities was not significant different between both groups (P > .05). Conclusions - The present study found that neuroimaging was unnecessary for the primary headache patients.

Isolated lymphomatoid granulomatosis of the central nervous system: A case report and literature review.

Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoproliferative disease which can involve multiple organs of the body and is most common in the lungs. Its pathological features are proliferation of large atypical B-cells related to Epstein-Barr virus, T-cell infiltration and tissue necrosis. This disease is rare, and LYG which uniquely involves the central nervous system (CNS) is extremely rare. In this paper, we report a case of isolated lymphomatoid granulomatosis of the CNS (iCNS-LYG) diagnosed by histological biopsy and we review the clinical features of all similar cases reported in the past 46 years. A total of 49 cases of iCNS-LYG have been reported to date. The clinical, imaging and pathological features of iCNS-LYG are discussed in combination with a literature review.

Characteristics of Headache After an Intracranial Endovascular Procedure: A Prospective Observational Study.

BACKGROUND: Two editions of the International Classification of Headache Disorders (ICHD) diagnostic criteria for "Headache attributed to an intracranial endovascular procedure" have been published, in 2004 and 2013.1,2 Despite studies that have suggested that the former is not very practical, the ICHD-3 beta did not contain major changes. Moreover, so far no consensus exists regarding characteristics of headache after intracranial endovascular procedure. Thus, there is a need for sound suggestions to improve the ICHD-3 beta diagnostic criteria. METHODS: Using a prospective design, we identified consecutive patients with unruptured intracranial aneurysms (UIAs) with neuroendovascular treatment from January 2014 to December 2014. RESULTS: In total, 73 patients were enrolled, and 58 patients ultimately completed the 6-month follow-up. After the procedure, five of the 29 patients (17.2%) with pre-existing headache experienced marked worsening after the procedure, while seven of the 29 patients without prior headache developed new-onset headache post-procedurally. The headaches started within 24 hours, with a mean duration of 24-72 hours. The headaches were moderate to severe. The eligibility of these events to be considered headaches caused by neuroendovascular procedures according to the ICHD-3 beta diagnostic criteria for designation was far from ideal. CONCLUSIONS: Most cases of markedly worsening headaches and new-onset headaches started within 24 hours and persisted longer than that specified in the ICHD-3 beta diagnostic criteria. Moreover, considering that some items are not very practical, the ICHD-3 beta diagnostic criteria should be revised in the light of recent literature reports.

[Only overlapping stents therapy for intracranial vertebral artery dissection aneurysms].

OBJECTIVE: To evaluate the feasibility, safety, clinical, and angiographic follow-up of only overlapping stents therapy for intracranial vertebral artery dissection aneurysms (VADA). METHODS: Eight consecutive patients (6 men, 2 women; mean age 46.8 years ranging from 34 to 62 years) with intracranial VADA admitted to Department of Neurology, Chinese People's Liberation Army General Hospital from June 2008 to June 2014 were retrospectively reviewed. All patients were diagnosed intracranial VADA by MRI or digital subtraction angiography (DSA). All patients were treated by only overlapping stents therapy under general anesthesia. In the endovascular treatment process 2 to 3 Solitaire, Neuroform or Wingspan self-expandable stents were overlapping implanted in the segment of the aneurysms. All patients received routine antiplatelet therapy before and after endovascular treatment. RESULTS: The operative procedures were succeeded in all patients. Eight patients were implanted 18 stents (2 patients, 3 stents; 6 patients, 2 stents). The stents were located accurately and implanted smoothly, none perioperative complications occurred. All patients lived and worked normally and had no recurrent symptoms on follow-up of 6 to 48 months. All patients performed DSA reexamination on follow-up. The aneurysm blocked in 2 patients, the size lessened in 2 patients, and the size had no change in 3 patients. CONCLUSIONS: Only overlapping stents therapy for treating intracranial VADA is feasible and has good operation safety. Preliminary follow-up results show that it can reduce the probability of thrombosis or hemorrhage and can improve the patients' life quality.

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.

DNA methylation of RAMP1 gene in migraine: an exploratory analysis.

BACKGROUND: Receptor activity modifying protein 1(RAMP1) is a key receptor subunit of calcitonin gene related peptide (CGRP) playing a critical role in migraine. But variations in RAMP1 gene have not been found to link with migraine. Still it is elusive that DNA methylation at RAMP1 promoter is associated with migraine. METHODS: A total of 51 blood DNA samples from 26 patients with migraine and 25 matched healthy controls were collected, extracted and treated with bisulfate. Subsequently DNA methylation levels at RAMP1 promoter region were measured using Sequenom Mass ARRAY systems. RESULTS: Among 13 detected CpG sites or units at RAMP1 promoter region, there were no significant differences between the migraine and control groups, but indicating a low methylation trend overall in migraine group (total average methylation level: 8.41 % ±1.92 % vs. 9.90 % ± 3.88 %, p = 0.197). Stratification analysis showed that methylation level at (+25, +27, +31, related to the transcription start site) CpG unit was higher in migraineurs with migraine family history compared to those without (13.92 % ± 5.97 % vs. 8.77 % ± 6.61 %, p = 0.034), and methylation level at (+89, +94, +96) CpG unit was lower in migraine female than that in healthy female (2.18 % ± 1.91 % vs. 5.85 % ± 5.41 %, p = 0.02). For female with methylation level at (+89, +94, +96) CpG unit below 3.50 %, the probability of being a migraine patient was significantly higher than those with methylation level above the threshold (OR: 7.313; 95%CI: 1.439-37.164). CONCLUSIONS: This study provides the first evidence that DNA methylation at RAMP1 promoter might play a role in migraine. A low methylation trend overall was presented in migraine subjects, and two CpG units were observed to link with positive migraine family history and female migraine, respectively. Lower methlytion level at (+89, +94, +96) CpG unit may be a risk of migraine in females.

The second to fourth digit ratio (2D:4D): a risk factor of migraine and tension-type headache.

BACKGROUND: Migraine and Tension-type headache (TTH) are common and disabling primary headache disorders. They are more prevalent in females. The second to fourth digit ratio (2D:4D) is sexually dimorphic in humans and is considered to be a marker for the balance of prenatal testosterone and estrogen exposure. Therefore, we investigated the hypothesis that prenatal sex steroids constitute an independent risk factor for adult headaches later in life. METHODS: A total of 891 individuals (303 males, 588 females) of 18-68 years in age (a mean of 37.0 ± 10.1 years), including 279 migraine, 300 TTH, and 312 healthy subjects were enrolled. The 2D:4D ratio was measured by a single investigator using a digital Vernier caliper. RESULTS: The females in the migraine group had lower 2D:4D ratios than those in the control group (left hand: 0.947 ± 0.034 vs. 0.955 ± 0.038, p = 0.048; right hand: 0.952 ± 0.035 vs. 0.965 ± 0.037, p = 0.001). There was a similar relationship between the TTH group and the control group (left hand: 0.946 ± 0.034 vs. 0.955 ± 0.038, p = 0.034; right hand: 0.954 ± 0.035 vs. 0.965 ± 0.037, p = 0.005), although this was not observed in males. Males showed lower 2D:4D ratios than females for the right hand in the control group (0.954 ± 0.039 vs. 0.965 ± 0.037, p = 0.015). No significant difference was found in the left hand. CONCLUSIONS: These results suggested that the 2D:4D ratio is a risk factor of migraine and TTH and that the balance of prenatal estrogen and testosterone in utero may impact adult primary headache disorders.

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.