A Clinical Retrospective Study of Recurrent Painful Ophthalmoplegic Neuropathy in Adults.

INTRODUCTION: Recurrent painful ophthalmoplegic neuropathy (RPON) is quite rare and usually occurs in children. In this report, we describe the clinical features, diagnosis, and treatment of RPON in adults. METHODS: A retrospective review was conducted of all RPON cases seen and treated at the Zhongshan Ophthalmic Center of Sun Yat-sen University and the Department of Neurology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, over the period from January 2016 to May 2020. RESULTS: A total of 8 patients (3 males and 5 females) with a mean age of 42.9 years (range: 23-64 years) met the diagnostic criteria of RPON. Headaches were present prior to the onset of ophthalmoplegic neuropathy in 50% of these patients, while in the remaining 50%, headaches occurred simultaneously with eye symptoms. The degree of these headaches was described as being mild or moderate. Abnormalities involving cranial nerve III were the most frequently reported pathologies (6 cases, 75%), followed by nerve VI (4 cases, 50%) and then nerve IV (1 case, 12.5%) (more than one nerve was affected in some cases). Following either with glucocorticoid treatment or with observation only, symptoms and signs within all 8 patients completely dissipated within 3-28 days. CONCLUSIONS: All adult cases of RPON along with their clinical features as reported here were similar to those of children.

Involvement of 5-Hydroxytryptamine Receptor 2A in the Pathophysiology of Medication-Overuse Headache.

BACKGROUND: Recent studies indicated that analgesic overuse upregulated 5-hydroxytryptamine receptor 2A (5-HT2AR) and subsequently activated nitric oxide synthase (NOS) and thus induced latent sensitization, which provided a mechanistic basis for medication-overuse headache (MOH). Moreover, glycogen synthase kinase-3ß (GSK-3ß) was regulated by serotonin receptors and the phosphorylation of GSK-3ß affected NOS activity, indicating that GSK-3ß could be involved in the regulation of NOS activity by 5-HT2AR in MOH pathophysiology. Herein, we performed this study to investigate the role of 5-HT2AR in MOH pathophysiology and the role of GSK-3ß in the regulation of NOS activity by 5-HT2AR. MATERIALS AND METHODS: Wistar rats were daily administered with paracetamol (200 mg/kg) for 30 days to set animal models for pre-clinical MOH research. After the rat MOH models were successfully established, the expression of 5-HT2AR and NOS, GSK-3ß activity in trigeminal nucleus caudalis (TNC) were assayed. Then, 5-HT2AR antagonist ketanserin and agonist DOI were applied to investigate the effect of 5-HT2AR on NOS activity in TNC of MOH rats, and GSK-3ß antagonist LiCl and agonist perifosine were applied to explore the role of GSK-3ß in the activation of NOS by 5-HT2AR. RESULTS: We found that the expression of 5-HT2AR and NOS, GSK-3ß activity were enhanced in TNC of MOH rats. 5-HT2AR modulator regulated the activity of NOS and GSK-3ß in TNC of MOH rats, and drugs acting on GSK-3ß affected NOS activity. CONCLUSION: These data suggest that GSK-3ß may mediate the activation of NOS by 5-HT2AR and underline the role of 5-HT2AR in MOH pathophysiology.

Late-onset MADD in Yemen caused by a novel ETFDH mutation misdiagnosed as ADEM.

We report a case of late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) with recurrent abdominal pain, vomiting, and impaired consciousness as the initial symptoms in Yemen; the case showed distinctive characteristics from those of Asian or Caucasian patients. Initially, he was misdiagnosed with pancreatitis, acute disseminated encephalomyelitis(ADEM), and fatty liver. Final diagnosis was further confirmed by electromyography, muscle biopsy, uric organic acid analysis, and a novel missense mutation in exon 7 (c.807A>C) of ETFDH was identified by next-generation sequencing. To our knowledge, we report this mutation in an adult MADD patient as well as late-onset MADD in a Middle East country for the first time. MADD is characterised by varied genotypes and broad spectrum of clinical manifestations among different populations and ages, which requires more attention and awareness in the clinic.

Radiation Outcome in Mechanical Thrombectomy of Acute Ischemic Stroke.

OBJECTIVE: Mechanical thrombectomy is recommended for acute ischemic stroke (AIS) with large artery occlusion. Radiation during the endovascular procedure would increase the risk of skin diseases. We sought to identify radiation outcomes during mechanical thrombectomy. METHODOLOGY: We prospectively collected and analyzed radiation parameters during mechanical thrombectomy in 41 patients affected with acute cerebral artery occlusion. RESULTS: There were 41 cases (68.73 ± 11.05 years) in this study, with a National Institute Health Stroke Scale (NIHSS) score of 15.66 ± 5.94. The time parameters were recorded as following: 84.45 ± 31.66 min (operation duration), 129.71 ± 81.14 s (angiographic run), 16.02 ± 11.03 min (fluoroscopy) and 18.19 ± 11.14 min (angiographic exposure). The doses produced in the procedure were: 1276.43 ± 1647.56 mGy (shot dose), 607.26 ± 412.34 mGy (fluoroscopy) and 1635.52 ± 593.65 mGy (angiographic exposure). Further analysis discovered no association between NIHSS and these time and radiation parameters (P > 0.05). CONCLUSION: This study provided the description of radiation details during mechanical thrombectomy for acute cerebral artery occlusion. The stroke severity would not influence the procedure parameters.

Cognitive Decline in Chronic Migraine with Nonsteroid Anti-inflammation Drug Overuse: A Cross-Sectional Study.

Background: Chronic migraine with medication overuse headache (CM-MOH) is the most common type of chronic migraine, and it increases risk of stroke and white matter lesions. These pathologic changes could induce cognitive decline. However, the alteration of cognitive function in CM-MOH patients is not established. Therefore, we took this study to reveal the cognitive performances in CM-MOH. Methods: This cross-sectional study was conducted between December 2015 and January 2017. Patients were divided into CM-MOH, CMwoMOH (chronic migraine without medication overuse), and MO (migraine without aura) groups. Cognitive function was assessed in all cases during interictal periods using Addenbrooke's Cognitive Examination Test (ACE-R), Trail Making Test A/B (TMT A/B), and Digit Symbol Test (DST). Detailed headache characteristics and evaluation of anxiety, depression, and living and sleep quality were collected. Results: 116 patients were included in this study. There were 21 CM-MOHs, 20 CMwoMOHs, 35 MOs, and 40 controls. Age and education were the independent risk factors of cognitive decline (P < 0.05). After adjusting, the risk of cognitive decline was higher in CM compared with control in ACE-R score and language fluency (P < 0.05). In addition, CM-MOH sufferers were in higher risk of memory and executive dysfunction (P < 0.05). The cognitive function had no difference between CM-MOH and CMwoMOH (P > 0.05). Meanwhile, CM-MOH got significantly higher scores than MO in anxiety and depression, with poorer performances in sleep and life quality (P < 0.05). Conclusion: The risk of cognitive decline increased in chronic migraine patients. Nonsteroid anti-inflammatory drugs overuse had no influence on cognitive performances among chronic migraine sufferers.

Acute phase serum cathepsin S level and cathepsin S/cystatin C ratio are the associated factors with cerebral infarction and their diagnostic value for cerebral infarction.

Cathepsin S plays an important role in the pathogenesis of several cardiovascular diseases; however, the relationship between serum cathepsin S and cerebral infarction (CI) is still unknown. This study aimed to investigate the relationship between acute phase serum cathepsin S level and cerebral infarction. A total of 202 stroke patients were enrolled into this study, and were divided into cerebral infarction (n = 140) group and non-cerebral infarction group (non-CI, n = 62). Fifty healthy individuals were recruited as the control group. Serum levels of cathepsin S and cystatin C were measured at days 1, 7, and 14 posthospitalization. Compared to the non-CI group, the CI group had significantly higher rates of hypertension, dyslipidemia, and smoking (all P < 0.05). The CI group had significantly higher cathepsin S levels and cathepsin S to cystatin C ratio (CatS/CysC) at both days 1 and 7 posthospitalization (both P < 0.05). Multivariate logistic regression analysis demonstrated that cathepsin S level (day 7) and CatS/CysC (days 1 and 7) were the associated factors with CI (all P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the Area Under Curve (AUC) value of CatS-day7, CatS/CysC-day1, and CatS/CysC-day7 were 0.726 (95% CI: 0.652-0.800, P < 0.001), 0.641 (95% CI: 0.559-0.723, P = 0.001), and 0.721 (95% CI: 0.645-0.797, P = 0.039), respectively. Cathepsin S and CatS/CysC were associated with acute CI, and may have the potential to be the diagnostic biomarkers for CI. Our findings help to better understand the role of serum cathepsin S level in CI.

MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-κB and PI3K-Akt pathways.

Recent evidence have suggested that neuroinflammation and ischemia induce the activation of two different types of reactive astrocytes, termed A1 and A2. Additionally, A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative diseases, such as Alzheimer's disease (AD). In the current study, we constructed an Aß42-activated microglia-conditioned medium to induce A1 astrocytic activation via secretion of interleukin 1α, tumor necrosis factor, and complement component 1q in vitro, and indicated the regulatory role of milk fat globule epidermal growth factor 8 (MFG-E8) on A1/A2 astrocytic alteration through the downregulation of nuclear factor-κB and the upregulation of PI3K-Akt. This study showed that MFG-E8 suppressed A1 astrocytes and holds great potential for the treatment of AD.

MFG-E8 inhibits Aß-induced microglial production of cathelicidin-related antimicrobial peptide: A suitable target against Alzheimer's disease.

Neuroinflammation plays a pivotal role in the incidence and progression of Alzheimer's disease (AD). Cathelicidin-related antimicrobial peptide (CRAMP) is critically involved in the innate neuronal responses of chronic neuroinflammation in AD and thus plays a key role in the disease. Here, we show that Aß42 induced microglial production of CRAMP, which was effectively inhibited by milk-fat globule-epidermal growth factor 8 (MFG-E8). Production of CRAMP was associated with activation of ERK1/2, p38 and phospho-P65-NF-kB upregulation. Additionally, the phosphorylation of these signaling proteins was also reversed by MFG-E8. Pre-incubation with signaling inhibitors confirmed that MFG-E8 has a regulatory role on CRAMP through MAPK and NF-kB signaling pathways. MFG-E8 treatment may thus be a potential pharmacotherapy for chronic inflammation in AD.

The association between brain-derived neurotrophic factor gene polymorphism and migraine: a meta-analysis.

BACKGROUND: Migraine is a recurrent headache disease related to genetic variants. The brain-derived neurotrophic factor (BDNF) gene rs6265 (Val66Met) and rs2049046 polymorphism has been found to be associated with migraine. However, their roles in this disorder are not well established. Then we conduct this meta-analysis to address this issue. METHODS: PubMed, Web of Science and Cochrane databases were systematically searched to identify all relevant studies. Odds ratio (OR) with corresponding 95% confidence interval (CI) was used to estimate the strength of association between BDNF gene rs6265 and rs2049046 polymorphism and migraine. RESULTS: Four studies with 1598 cases and 1585 controls, fulfilling the inclusion criteria were included in our meta-analysis. Overall data showed significant association between rs6265 polymorphism and migraine in allele model (OR = 0.86, 95%CI: 0.76-0.99, p = 0.03), recessive model (OR = 0.84, 95%CI: 0.72-0.98, p = 0.03) and additive model (GG vs GA: OR = 0.85, 95%CI: 0.72-1.00, p = 0.04), respectively. We also found significant association between rs2049046(A/T) polymorphism and migraine in allele model (OR = 0.88, 95%CI: 0.79-0.98, p = 0.02), recessive model (OR = 0.80, 95%CI: 0.67-0.96, p = 0.02) and additive model (AA vs TT: OR = 0.72, 95%CI: 0.57-0.92, p = 0.008; AA vs AT: OR = 0.81, 95%CI: 0.67-0.99, p = 0.03), respectively. CONCLUSION: Our meta-analysis suggested that BDNF rs6265 and rs2049046 polymorphism were associated with common migraine in Caucasian population. Further studies are awaited to update this finding in Asian population and other types of migraine.

MFG-E8 Selectively Inhibited Aß-Induced Microglial M1 Polarization via NF-κB and PI3K-Akt Pathways.

Activated microglia are classified into two specific states: classically activated (M1) and alternatively activated (M2) subtypes. It is believed that the polarization of M1/M2 phenotype plays an important role in Alzheimer's disease (AD). However, the mechanisms regulating this process remain unclear. Thus, we addressed this question focusing on milk fat globule epidermal growth factor 8 (MFG-E8). MFG-E8 is a unique protein which can bind to microglia and regulate its inflammatory responses. It is speculated that it might play a role in the balance of microglial polarization. In the current study, we used fibril Aß42 in vitro to stimulate mouse primary microglial cultures and found subsequent M1 marker expression, along with retained M2 marker production. Then, we discovered that MFG-E8 pretreatment reversed the increased trend of M1 markers and the decreased expression of M2 markers, which were induced by Aß42. Moreover, MFG-E8 effects could be effectively blocked by an MFG-E8 antibody. Further analysis on the signaling pathways showed that NF-κB upregulation and Akt downregulation in microglial cultures were observed after Aß42 incubation. And the alteration of these pathways could also be reversed by MFG-E8. We then assessed the effects of NF-κB and PI3K-Akt on M1/M2 alteration using their specific inhibitors. Pyrrolidine dithiocarbamate, a NF-κB inhibitor, inhibited M1 marker expression; moreover, LY294002, an Akt inhibitor, enhanced M1 marker expression. Our study indicated the regulatory role of MFG-E8 on microglia M1/M2 alteration for the first time, providing a basis for understanding the potential role of microglia activation in AD.

Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats.

BACKGROUND: Antioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats. METHODS: The expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot. Immunofluorescence was used to demonstrate the cell-specific localization of Nrf2 in TNC. Sulforaphane, a Nrf2 activator, was administered to NTG-induced rats. Then, the number of c-Fos- and nNOS-immunoreactive neurons in TNC was evaluated using immunofluorescence, and c-Fos and nNOS protein levels were quantified using western blot. Von Frey hair testing was used to evaluate the tactile thresholds of rats at different time points in different groups. RESULTS: Total cellular and nuclear levels of the proteins Nrf2, HO1, and NQO1 were elevated in TNC after NTG injection, and Nrf2 was found to be located in the nucleus and cytoplasm of the neurons. Sulforaphane pretreatment significantly increased the nuclear Nrf2, HO1, and NQO1 levels in TNC. In addition, sulforaphane exposure effectively inhibited the expression of nNOS and c-Fos, reduced the number of nNOS and c-Fos immunoreactive neurons in TNC, and attenuated the tactile thresholds induced by NTG injection. CONCLUSION: Oxidative stress was involved in nitroglycerin-induced hyperalgesia. Activation of the Nrf2/ARE pathway inhibited the activation of TGVS and prevented the induction of hyperalgesia. Sulforaphane might therefore be an effective agent for hyperalgesia. Further studies are needed to discover the underlying mechanisms of the process.

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.

Chronic Obstructive Pulmonary Disease as a Risk Factor for Cognitive Dysfunction: A Meta-Analysis of Current Studies.

Cognitive dysfunction has been shown to be associated with many risk factors, such as smoking, diabetes, and body mass index. Chronic obstructive pulmonary disease (COPD), a common disease within the elderly population, has also been found to be related to cognitive decline. However, whether COPD is a risk factor of cognitive dysfunction is not well established. The purpose of this meta-analysis is to investigate the role COPD plays in cognitive dysfunction. PubMed, Cochrane library and Web of Science databases were searched. Three cohort studies and eleven cross-sectional studies were found to be eligible. According to our results, COPD patients had a higher risk of cognitive dysfunction than controls (OR [odds ratio]: 1.72; 95% CI, 1.12-2.65; p = 0.01). The exacerbation of COPD was strongly correlated with cognitive decline. COPD patients performed worse than controls on the Mini- Mental State Examination test, but the results were not statistically significant (OR: -0.79; 95% CI, [-1.78, 0.19]; p = 0.11). Thus, more attention should be given to the occurrence of cognitive decline in COPD patients. The prevention and control of COPD exacerbation are critical.

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.

Curcumin inhibits Aß-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways.

Amyloid ß (Aß) plays an important role in Alzheimer's disease (AD) by inducing microglia activation. Once activated, microglial cells promote the release of reactive species and cytokines that are known to enhance immune responses in AD brain. Thus, negative regulators of microglia activation are considered as potential therapeutic candidates for AD. Curcumin, the major yellow pigment in turmeric (Curcuma longa), is proposed for its anti-inflammatory properties. Several studies have indicated the suppressive effects of curcumin on LPS-induced microglia activation and MAPK activities. However, the effects of curcumin on Aß-treated microglia and the possible mechanisms are still not fully understood. In the present study, we found that curcumin improved microglial viability against Aß42 in a time- and dose-dependent manner and remarkably suppressed Aß42-induced CD68 expression. Moreover, curcumin concentration-dependently abolished Aß42-induced interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in mRNA and protein levels in microglia. Besides, curcumin exerted an inhibitory effect on phosphorylation of ERK1/2 and p38 in Aß42-activated microglia. Further experiments indicated that blockage of ERK1/2 and p38 pathways reduced inflammatory cytokines production from microglia. These results show that curcumin suppresses ERK1/2 and p38 signaling, thus, attenuating inflammatory responses of brain microglia.

Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in Aß1-42 insult in vitro.

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer's disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aß1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aß1-42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aß1-42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1.

Efficacy of intravenous propacetamol hydrochloride in the treatment of an acute attack of migraine.

BACKGROUND: Triptans are a family of selective serotonin (5-HT1B/1D) receptor agonists that are widely used to treat acute migraine attacks. Their efficacy is limited by side effects and the gastrointestinal manifestations of migraine. AIM: To compare the efficacy of a single intravenous administration of propacetamol, a prodrug of paracetamol (acetaminophen) with a single dose of oral rizatriptan in treating acute migraine attacks. METHODS: Patients were selected from those who presented to the emergency room with a diagnosed migraine attack and who had not previously taken any analgesics. They were randomized into 2 groups: treatment with a single 1g IV dose of propacetamol or with a single oral dose of 5mg rizatriptan. Their Visual Analogue Scale (VAS) pain scores were assessed before and at 30, 60, and 120min after treatment. RESULTS: The patients who received the propacetamol had significantly improved VAS scores at 60min compared to the rizatriptan group. There were no significant differences in VAS scores at 30 or 120min post-treatment. CONCLUSION: Propacetamol is either equivalent or superior in efficacy to rizatriptan for treating acute migraine attacks, while having the advantage of parenteral administration in patients whose migraines are accompanied by nausea and vomiting.

Prevalence and burden of headache disorders in two neighboring provinces of China.

To our knowledge, studies concerning the prevalence and burden of primary headache in China are limited to specific regions without comparison of different districts. A survey in a different area with similar climate and culture may enhance our knowledge of the factors causing primary headache and the burden of headache. We conducted a 1 year survey on the prevalence and burden of primary headache in the Chinese provinces of Guangdong and Guangxi. Our study also evaluated the factors behind similarities and differences affecting prevalence in the two regions of study. The survey methodology, which was used in an Expanded Program on Immunization by the World Health Organization, was adopted to investigate the prevalence and burden of headache patients. Random samples of 372 local residents in Guangdong and 182 local residents in Guangxi aged 18-65 years were invited to a face-to-face interview. The education level and mean household income were higher in Guangdong (p<0.05). The 1 year prevalence of primary headache was 22.6% (84/372) in Guangdong and 41.2% (75/182) in Guangxi (p<0.001). The average financial burden of primary headache is 2.1% and 3.7% of the mean household income in Guangdong and Guangxi, respectively (p=0.001). The district with lower economic status had a higher prevalence of primary headache, and inevitably bears a heavier burden even with the same disease cost.

5-HT7 receptors are involved in neurogenic dural vasodilatation in an experimental model of migraine.

Neurogenic dural vasodilation has been demonstrated to play an important role in migraine. 5-HT(7) receptors have been found on trigeminal nerve endings and middle meningeal arteries and demonstrated involved in the dilatation of meningeal arteries. The aim of the present study was to demonstrate whether 5-HT(7) receptors are involved in neurogenic dural vasodilation in migraine. The neurogenic dural vasodilation model of migraine was used in this study. Unilateral electrical stimulation of dura mater was performed in anesthetized male Sprague-Dawley rats. Animals were pretreated with selective 5-HT(7) receptor agonist AS19, 5-HT(7) receptor antagonist SB269970, 5-HT1B/1D receptor agonist sumatriptan, or vehicles. Blood flow of the middle meningeal artery (MMA) was measured by a laser Doppler flowmetry. AS19 significantly increased the basal and stimulated blood flows of the middle meningeal artery following electrical stimulation of dura mater, and its effect was dose dependent at the early stage. SB269970 and sumatriptan significantly reduced the basal and stimulated blood flows of middle meningeal artery. The present study demonstrates for the first time that 5-HT(7) receptors are involved in neurogenic dural vasodilation evoked by electrical stimulation of dura mater and maybe of relevance in the pathophysiology and treatment of migraine.

White matter lesions in chronic migraine with medication overuse headache: a cross-sectional MRI study.

Analgesic overuse often happens to migraine patients, especially chronic migraineurs, and migraine has been demonstrated to be associated with white matter lesions (WMLs). The aim of this study was to investigate the relationship between medication overuse headache (MOH) and WMLs in chronic migraine (CM) patients. Subjects were enrolled and divided into three groups: healthy controls, CM without MOH (CMwoMOH), and CM with MOH (CM-MOH). Most of the CM patients used non-steroidal anti-inflammatory drugs (NSAIDs) as acute headache medications. All the participants underwent magnetic resonance imaging scans and images were obtained for WML evaluation with semiquantitative scales. One hundred and forty-one participants were included, 45 of them for controls, 38 for CMwoMOH, and 58 for CM-MOH. In women, CMwoMOH patients had a higher prevalence of high WML load compared with controls and CM-MOH patients. In men, however, all the study groups showed no differences in the prevalence of high WML load. CMwoMOH women had increased risks of high deep white matter lesion (DWML) load compared with controls, while they had no risks of high periventricular white matter lesion (PVWML) load. CM-MOH women had no risks of high DWML load, but they had reduced risks of high PVWML load. The association of CM-MOH with high WML load in women was not changed when compared with CMwoMOH. Age was independently associated with high WML load among women. These data suggest that MOH caused by NSAIDs is not a risk factor for WMLs. Rather, NSAID overuse probably protects MOH patients from WMLs through anti-inflammatory effects.