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Objective The presence of aura is rare in cluster headache, and even rarer in other trigeminal autonomic cephalalgias. We hypothesized that the presence of aura in patients with trigeminal autonomic cephalalgias is frequently an epiphenomenon and mediated by comorbid migraine with aura. Methods The study retrospectively reviewed 480 patients with trigeminal autonomic cephalalgia in a tertiary medical center for 10 years. Phenotypes and temporal correlation of aura with headache were analyzed. Trigeminal autonomic cephalalgia patients with aura were further followed up in a structured telephone interview. Results Seventeen patients with aura (3.5%) were identified from 480 patients with trigeminal autonomic cephalalgia, including nine with cluster headache, one with paroxysmal hemicrania, three with hemicrania continua, and four with probable trigeminal autonomic cephalalgia. Compared to trigeminal autonomic cephalalgia patients without aura, trigeminal autonomic cephalalgia patients with aura were more likely to have a concomitant diagnosis of migraine with aura (odds ratio [OR] = 109.0, 95% CI 30.9–383.0, p Interpretation In most patients with trigeminal autonomic cephalalgia, the presence of aura is mediated by the comorbidity of migraine with aura. Aura directly related to trigeminal autonomic cephalalgia attack may exist but remains rare. Our results suggest that aura may not be involved in the pathophysiology of trigeminal autonomic cephalalgia.

Objective Headache disorders like migraine show geographic and ethnic differences between Asian and European/North American countries. In cluster headache, these differences are rarely mentioned and discussed. This article aimed to review the characteristics of cluster headache in Asian countries and compare the clinical features to those in European and North American populations. Methods We conducted a narrative literature review on the demographics, clinical presentations, and treatments of cluster headache in Asian countries. Results Patients with cluster headache in Asian populations showed a stronger male predominance compared to European and North American populations. Chronic cluster headache was rare in Asian countries. The clinical presentation of restlessness was not as common in Asian as it was in European and North American countries, and Asian patients with aura were extremely rare. Patients in Asian countries may have a lower circadian rhythmicity of cluster headache and a lower headache load, as demonstrated by lower attack frequencies per day, bout frequencies, and bout durations. Conclusions Regional differences in the presentation of cluster headache exist. Greater awareness for cluster headache should be raised in Asian regions, and further studies are warranted to elucidate the mechanisms behind observed differences.

Migraine encompasses a broader spectrum of sensory symptoms than just headache. These “other” symptoms, eg, sensory phobias, cognitive and mood changes, allodynia, and many others indicate an altered sensitivity to sensory input which can be measured, in principle, by quantifying sensory threshold changes longitudinally over time. Photophobia, for example, can be quantified by investigating the discomfort thresholds towards the luminance of light. The aim of this review is to look into how thresholds change in patients with migraine. We performed a PubMed search up to June 2018 targeting all peer-reviewed articles evaluating the changes in threshold, sensory phobia, or sensitivity in patients with migraine. Migraineurs, in general, exhibit lower sensory thresholds compared with healthy controls. These threshold changes seem to follow the different phases during a migraine cycle. In general, thresholds reach a nadir when the headache starts (the ictal phase), rise after the headache ends, and then gradually descend towards the next attack. The sensory modality of measurement – mechanical, thermal, or nociceptive – and the location of measurement –trigeminal vs somatic dermatome – also influence the sensory threshold. Functional imaging studies provide evidence that the hypothalamo-thalamobrainstem network may be the driving force behind the periodic threshold changes. In summary, there is evidence in the literature that migraine could be understood as a periodic sensory dysregulation originating from the brain. Nevertheless, the interstudy discrepancy is still high due to different study designs and a lack of focus on distinct migraine phases. Further well-designed and harmonized studies with an emphasis on the cyclic changes still need to be conducted.

Background Migraine is associated with syncope. We investigated risk factors for syncope and burden of syncope in migraine patients. Methods Participants were recruited from a headache clinic. All participants provided information on lifestyle, co-morbidity, syncope, headache and suicide, and completed the MIDAS and HADS questionnaires. Genetic data were available for a subset of participants. Risk of syncope in relation to participant’s characteristics and migraine susceptibility loci, and risks of psychological disorders associated with syncope, were calculated using logistic regression. Results Underweight, regular tea intake, diabetes mellitus, and migraine with aura were associated with increased syncope risks, with adjusted ORs of 1.76 (95% CI 1.03–3.03), 1.84 (95% CI 1.22–2.79), 4.70 (95% CI 1.58–13.95), and 1.78 (95% CI 1.03–3.10), respectively. Preliminary results showed that rs11172113 in LRP1 was associated with syncope risks. Comorbid syncope in migraine patients was associated with increased risks of depression (OR 1.95, 95% CI 1.18–3.22) and suicide attempt (OR 2.85, 95% CI 1.48–5.48). Conclusion Our study showed the potential roles of vascular risk factors in the association between migraine and syncope. Modifiable risk factors for syncope in patients with migraine include body mass index and tea intake. The debilitating psychological impact of co-morbid syncope in migraine patients warrants clinical attention of treating physicians.

Migraine is defined by attacks of headache with a specific length and associated symptoms such as photophobia, phonophobia and nausea. It is long recognized that migraine is more than just the attacks and that migraine should be understood as a cycling brain disorder with at least 4 phases: interictal, preictal, ictal and postictal. However, unlike the pain phase, the other phases are less well defined, which renders studies focusing on these phases susceptible to bias. We herewith review the available clinical, electrophysiological, and neuroimaging data and propose that the preictal phase should be defined as up to 48 hours before the headache attack and the postictal phase as up to 24 hours following the ictal phase. This would allow future studies to specifically investigate these migraine phases and to make study results more comparable.

Migraine encompasses a broader spectrum of sensory symptoms than just headache. These "other" symptoms, eg, sensory phobias, cognitive and mood changes, allodynia, and many others indicate an altered sensitivity to sensory input which can be measured, in principle, by quantifying sensory threshold changes longitudinally over time. Photophobia, for example, can be quantified by investigating the discomfort thresholds towards the luminance of light. The aim of this review is to look into how thresholds change in patients with migraine. We performed a PubMed search up to June 2018 targeting all peer-reviewed articles evaluating the changes in threshold, sensory phobia, or sensitivity in patients with migraine. Migraineurs, in general, exhibit lower sensory thresholds compared with healthy controls. These threshold changes seem to follow the different phases during a migraine cycle. In general, thresholds reach a nadir when the headache starts (the ictal phase), rise after the headache ends, and then gradually descend towards the next attack. The sensory modality of measurement-mechanical, thermal, or nociceptive-and the location of measurement-trigeminal vs somatic dermatome-also influence the sensory threshold. Functional imaging studies provide evidence that the hypothalamo-thalamo-brainstem network may be the driving force behind the periodic threshold changes. In summary, there is evidence in the literature that migraine could be understood as a periodic sensory dysregulation originating from the brain. Nevertheless, the interstudy discrepancy is still high due to different study designs and a lack of focus on distinct migraine phases. Further well-designed and harmonized studies with an emphasis on the cyclic changes still need to be conducted.

Aims The metabolic derangements in type 2 diabetes have been attributed to compositional changes in the gut microbiota. Metformin, the first-line treatment for type 2 diabetes, has been found to modulate the gut microbiota. However, no literature has reported the associations between the composition of the gut microbiota and glycemic durability to metformin monotherapy. Methods A total of 375 patients with type 2 diabetes were recruited, among which 14 and 11 patients were eligible as the metformin durable group and nondurable group, respectively. Fecal samples were collected to analyze the gut microbiota by Illumina sequencing of the 16S rRNA gene, and PICRUSt2 was adopted to infer microbial functional differences. Results Although the two groups had similar biochemical profiles and microbial metabolites, the pattern of microbiota clustering was different. The intra-group diversity was significantly reduced in the durable group. For the microbial metabolic pathways, the biosynthesis of thiamine and lipopolysaccharide was dominant in the durable group. Conclusions There were different compositions of gut microbiota with unique microbial metabolic pathways between type 2 diabetes with and without glycemic durability to metformin monotherapy. Microbial salvage by increasing thiamine biosynthesis might be beneficial for the metformin durable group to maintain optimal glycemic control.

Objective To evaluate whether the use of intraoperative dexmedetomidine (DEX) during lung cancer surgery may reduce the incidence of acute kidney injury (AKI). Design A retrospective study. Setting An academic hospital. Participants Data were collected from 1,207 adult patients who underwent resection for non-small-cell lung cancer between January 2004 and December 2012. Interventions None. Measurements and Main Results All patients had a general balanced anesthetic technique, and dexmedetomidine use was at the discretion of the anesthesiologist. Data analysis was done utilizing the Wilcoxon rank sum tests and Chi-square tests to compare continuous variables and categoric variables between the 2 groups, respectively. Multivariate logistic analysis with backward selection was fitted to find out factors for AKI incidence. Overall, 8.1% of the patients developed AKI during their hospital stay. There were no statistically significant differences in demographic, perioperative variables, and the incidence of AKI between patients who did and did not receive DEX. A logistic regression model was fitted to determine factors independently associated with AKI. Factors that were independently associated with AKI included body mass index, American Society of Anesthesiologists 3-4, hypertension, smoking status, and thoracotomy procedure. Discussion The authors hypothesized that DEX use would be associated with a decreased incidence of AKI in thoracic surgery; however, they were unable to prove this hypothesis. Their results did demonstrate that there are 5 factors independently associated with AKI.

Objective Whether migraine is associated with urinary calculi is an unresolved issue, although topiramate, a migraine-preventive agent, is known to contribute to this complication. This study investigates the association between migraine and the risk of urinary calculi. Methods We identified a total of 147,399 patients aged ≥18 years with migraine diagnoses recorded in the Taiwan National Health Insurance Research Database between 2005 and 2009. Each patient was randomly matched with one individual without headache using propensity scores. All participants were followed from the date of enrollment until urinary calculi development, death, or the end of 2010. Results The risk of urinary calculi was greater in the migraine than the control cohort (adjusted hazard ratio (aHR), 1.58; 95% confidence interval (CI), 1.52–1.63; p Conclusions Our study showed migraine was associated with an increased risk of urinary calculi, independent of topiramate use. A higher frequency of clinic visits was associated with a greater risk.

Background:Hormonal changes in natural menstrual cycles are known to modulate and even worsen headache symptoms in migraineurs; however, the impact of oral contraceptive pills (OCP), including combined oral contraceptive (COC) and progestogen-only pills on migraine symptomatology, is little investigated.Method:In this retrospective cohort study of 1758 migraine patients, data from 1032 female patients aged 15–45 years were accessed and their contraceptive methods, if any, were analyzed. Further comparisons were conducted between patients with OCP use and those without OCP use regarding the demographics, headache symptoms, and associated symptoms. Most OCP users in this study were assumed to have used COC, but information of individual hormone content of OCP was not collected. Patients with nonoral hormonal contraceptives were excluded for further comparison.Results:The use of OCP was common (47.8%) among the study cohort. Compared to those without OCP use ( n = 410), patients with OCP use ( n = 493) were younger (27.4 ± 7.0 vs. 32.8 ± 7.9, p < 0.001), had lower headache frequency (days per month, 11.1 ± 7.5 vs. 12.3 ± 8.8, p = 0.03), were less likely to have osmophobia (47.3 vs. 54.4%, p = 0.033) or cranial autonomic symptoms (44.8 vs. 53.2%, p = 0.013), and more commonly reported menstrually-related worsening of headache (52.3 vs. 42.4%, p = 0.012). The proportion of migraine with aura or other headache characteristics including severity, unilaterality, and pulsatile characteristic showed no differences between groups.Conclusion:Our data provide real-life information about contraceptive use among patients with migraine. The use of OCP is associated with differences in migraine symptomatology. Further studies are needed to determine whether this relationship is causal and any possible underlying mechanism.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterised by amyloid beta (Aβ) plaques and tau neurofibrillary tangles in the brain. Human apolipoprotein E (ApoE) is a lipid transport protein coded by the polymorphic APOE gene, with three major alleles: e2, e3 and e4. After age, the e4 allele is the greatest risk factor for developing sporadic AD, conferring an increased risk of 3–4 and 8–12 times for one or two copies of the allele, respectively. This risk is reported to vary by demographic factors including sex, ethnicity and geography. In order to understand the risk of ApoE e4 in relation to age, the primary risk factor for developing AD, we need to understand how the prevalence of APOE genotypes changes with age. Here, we present the first data on age-related prevalence of APOE e4 in AD in three AD cohorts in Australia and the USA. There is a significant association between age and e4 prevalence, particularly for e4 homozygotes, such that as age increases the prevalence of e4 decreases. Further studies on a random, population-based sample of the population are needed to provide more generalizable data, particularly in the >90-year-old age group.

Background.—The link between arterial thromboembolism and migraine is well-documented; however, few studies investigated the link between venous thromboembolism (VTE) and migraine. We aimed to evaluate the association between migraine and VTE and to examine whether demographics or comorbid risk factors modulate VTE development. Methods.—We conducted a cohort study accessing a nationwide claims-based database with an adult cohort of 102,159 neurologist-diagnosed migraine patients, and 102,159 nonheadache comparison subjects, matched on sex and propensity score for the diagnosis of migraine. Both cohorts were followed until the end of 2010, death, or VTE development. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards regression analyses and compared between the two groups. Results.—During a mean follow-up period of 4.2 years, VTE developed in 226 patients (460,047 person-years) in the migraine cohort and in 203 subjects (462,401 person-years) in the comparison cohort. Overall, likelihood of VTE for the migraine cohort did not differ from that in the comparison cohort (aHR 1.12; 95% CI, 0.92–1.35; P = .251). However, subgroup analysis by migraine subtypes (P = .004 for interaction) revealed an elevated risk of VTE in patients with migraine with aura (aHR 2.42; 95% CI, 1.40–4.19; P = .002), but not in those with migraine without aura. The association was not altered in subsequent subgroup analyses and sensitivity analyses. Conclusions Risk of VTE development is elevated specifically in patients diagnosed with migraine with aura. This association suggests a linked disease mechanism and warrants further exploration.

Idiopathic intracranial hypertension (IIH) is a rare disorder that typically affects obese women of childbearing age, but can also occur in paediatric populations. Patients usually present with diffuse, daily headache and visual disturbances, but either symptom can occur in isolation. Patients with IIH often have papilloedema; however, IIH without papilloedema is fairly common in patients with chronic daily headache. The pathogenesis of IIH is unknown; the high incidence of comorbid bilateral transverse sinus stenosis (BTSS) in patients with IIH suggests that the two conditions are linked, although no direct causal relationship has been established. Cerebrospinal fluid (CSF) pressure monitoring or lumbar puncture-which provides immediate symptomatic relief-are important in making a diagnosis of IIH. Current treatments for IIH include weight reduction, medical treatment, CSF diversion surgery, optic nerve sheath fenestration and, potentially, endovascular stenting (in patients with BTSS). Prevention of visual loss (which can be substantial) is the main goal of treatment. Residual headache and IIH recurrence are not uncommon after treatment, and regular follow-up is, therefore, warranted even in patients who achieve remission. This Review provides an update of current knowledge of the aetiology, pathophysiology and treatment of IIH.

Headache disorder is a major public health issue and is a great burden for the person, the health care system, and society. This article reviews epidemiological surveys of primary headache disorders including migraine and tension-type headache (TTH) among adults in the Asia-Pacific region using the International Classification of Headache Disorders (ICHD), first or second edition. Chronic daily headache (CDH), which is not an official diagnosis in the ICHD, was also reviewed. In the Asia-Pacific region, the median (range) 1-year prevalence of primary headache disorders was 9.1% (1.5-22.8%) for migraine, 16.2% (10.8-33.8%) for TTH, and 2.9% (1.0-3.9%) for CDH. The 1-year prevalence of migraine and TTH were rather consistent; however, the extremes in the 1-year prevalence of migraine in earlier studies from Hong Kong (1.5%) and South Korea (22.3%) were not repeated in later surveys (Hong Kong: 12.5%; South Korea: 6%). According to the United Nations, the estimated population of the Asia-Pacific region was 3.85 billion in 2010, equaling to headache suffers of 350 million patients with migraine, 624 million with TTH, and 112 million with CDH; many remain to be treated. The prevalence of headache disorders has remained stable over the last 2 decades in this region, where the diversity of geography, race, and development is wide. Thus, the pursuit of better headache care in this region might be our next challenge.

Background The International Burden of Migraine Study (IBMS) showed chronic migraine (CM) was associated with a higher disease burden than episodic migraine (EM). However, in this study Asians with CM were underrepresented. Objectives We investigated if CM and EM differed in headache-related disability, health-related quality of life (HRQoL) and health care resource utilization in Taiwan. Methods This study recruited patients with EM and CM from two headache clinics in Taiwan. Diagnosis was made by physicians based on Silberstein-Lipton criteria. Participants completed a questionnaire including sociodemographics, Migraine Disability Assessment (MIDAS), EuroQol five-dimensions (EQ-5D), Migraine-Specific Quality of Life v2.1 (MSQ), Patient Health Questionnaire-4 (PHQ-4), productivity and health care resource utilization. Results A total of 331 patients (EM, n = 164 (49.5%); CM, n = 167 (50.5%)) completed the study. CM patients reported a significantly higher MIDAS score, lower generic (EQ-5D visual analogue scale score and EQ-5D index score) and migraine-specific (all three domains of MSQ) HRQoL, higher levels of anxiety and depression (PHQ-4 ≥ 6) and greater health care resource utilization and productivity loss than those with EM. Positive correlations were found between these instruments and levels of anxiety and depression. Conclusion Compared to EM, CM was significantly associated with higher disability, lower HRQoL and greater health care resource utilization and productivity loss.

Introduction: International Classification of Headache Disorders (ICHD-2) criteria for new daily persistent headache (NDPH) require tension-type headache features. Many patients with ‘new-onset persistent’ headache fail to fulfil such criteria due to prominent migrainous features. Subjects and methods: We reviewed all NDPH patients in our headache clinic, using the definition of persistent headache 3 months. The patients were dichotomised: patients meeting ICHD-2 criteria (NDPH-S) and patients failing to meet ICHD-2 criteria due to prominent migrainous features (NDPH-M). All patients had completed a structured intake form including demographics, headache profiles, Beck Depression Inventory (BDI), Short Form 36 (SF-36) Health Survey, and Migraine Disability Assessment (MIDAS). A telephone interview was conducted for follow-up. Results: A total of 92 NDPH patients were enrolled (59 (64.1%) NDPH-M, 33 (35.9%) NDPH-S). Between the two subgroups, the sociodemographics were indistinguishable, but the patients with NDPH-M had higher headache intensity, BDI scores, MIDAS scores, and lower scores of most SF-36 subscales. After an average of 2 years of follow-up, 57 (66%) had a good outcome (≥ 50% reduction in headache frequency). Cox proportional analysis showed that disease duration ≤ 6 months and NDPH-S diagnosis predicted good outcomes. Conclusion: Migrainous features were common in patients with NDPH. Unlike prior studies, our study showed NDPH-M represented a more severe subgroup with a poorer outcome compared with NDPH-S.

The purpose of our study was to evaluate the feasibility and treatment outcomes of recombinant adenovirus-p53 (rAd-p53, trademarked as Gendicine) combined with fractionated stereotactic radiotherapy (fSRT) in treatment of primary hepatocellular carcinoma (HCC). We randomly enrolled 40 patients with HCC treated by fSRT alone (fSRT group) or rAd-p53 combined with fSRT (combined group). Tumor size was 2–5.2 cm (average 3.2 cm). We prescribed 50 Gy in 10 fractions at the 50%–80% isodose line of the planning target volume for 2 weeks in two groups. The combined group was treated with two intratumoral injections of rAd-p53 on day 1 and 8 while fSRT started on day 3. Tumor response was assessed after treatment using modified WHO criteria. The follow-up period was 11–44 months (median 35 months). The overall response rate of fSRT group was 70%, with 4 patients showing complete response (20%), 10 partial response (50%) and 6 stable disease (30%). Correspondingly the overall response rate of combined group was 85%, with 7 patients showing complete response (35%), 10 partial response (50%) and 3 stable disease (15%). The 1-year survival rates of fSRT group and combined group were 70.0% and 90.0%, respectively. The 1-year disease-free survival rates of fSRT group and combined group were 65% and 85%, respectively. These treatments were well tolerated, because grade 3 or 4 toxicity was not observed. These results suggest that rAd-p53 combined with fSRT is a relatively safe and effective method for treating primary hepatocellular carcinoma compared with only fSRT. Thus, rAd-p53 combined with fractionated SRT may be preferred as a choice of local treatment for primary HCC when the patients are inoperable or when the patients refuse operation.

Many patients in the US require inter-hospital transfer for acute myocardial infarction (MI) care. Whether transferred patients are transitioned back to their local community as well as those hospitalized directly is unknown. Patients over age 65 in ACTION Registry-GWTG discharged alive after acute