A 12-week randomized double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine.

Omega-3 polyunsaturated fatty acids (PUFAs) may benefit migraine improvement, though prior studies are inconclusive. This study evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy individuals with EM participated in a 12-week randomized, double-blind, placebo-controlled trial from March 2020 and May 2022. They were randomly assigned to either the EPA (N = 35, 2 g fish oil with 1.8 g of EPA as a stand-alone treatment daily), or the placebo group (N = 35, 2 g soybean oil daily). Migraine frequency and headache severity were assessed using the monthly migraine days, visual analog scale (VAS), Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Pittsburgh Sleep Quality Index (PSQI) in comparison to baseline measurements. The EPA group significantly outperformed the placebo in reducing monthly migraine days (-4.4 ± 5.1 days vs. - 0.6 ± 3.5 days, p = 0.001), days using acute headache medication (-1.3 ± 3.0 days vs. 0.1 ± 2.3 days, p = 0.035), improving scores for headache severity (ΔVAS score: -1.3 ± 2.4 vs. 0.0 ± 2.2, p = 0.030), disability (ΔMIDAS score: -13.1 ± 16.2 vs. 2.6 ± 20.2, p = 0.001), anxiety and depression (ΔHADS score: -3.9 ± 9.4 vs. 1.1 ± 9.1, p = 0.025), and quality of life (ΔMSQ score: -11.4 ± 19.0 vs. 3.1 ± 24.6, p = 0.007). Notably, female particularly benefited from EPA, underscoring its potential in migraine management. In conclusion, high-dose EPA has significantly reduced migraine frequency and severity, improved psychological symptoms and quality of life in EM patients, and shown no major adverse events, suggesting its potential as a prophylactic for EM.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

Light Therapy in Chronic Migraine.

PURPOSE OF REVIEW: This review assesses the effectiveness and safety of light therapy, particularly green light therapy, as an emerging non-pharmacological treatment for chronic migraine (CM). It aims to highlight alternative or complementary approaches to traditional pharmacological remedies, focusing the need for diverse treatment options. RECENT FINDINGS: Despite sensitivity to light being a defining feature of migraine, light therapy has shown promising signs in providing substantial symptom relief. Studies have provided insights into green light therapy's role in managing CM. These studies consistently demonstrate its efficacy in reducing the frequency, severity, and symptoms of migraines. Additional benefits observed include improvements in sleep quality and reductions in anxiety. Importantly, green light therapy has been associated with minimal side effects, indicating its potential as a suitable option for migraine sufferers. In addition to green light, other forms of light therapy, such as infrared polarized light, low-level laser therapy (LLLT), and intravascular irradiation of blood (ILIB), are also being explored with potential therapeutic effects. Light therapies, especially green light therapy, are recognized as promising, safe, and non-pharmacological interventions for treating CM. They have been shown to be effective in decreasing headache frequency and enhancing the overall quality of life. However, current studies, often limited by small sample sizes, prompt more extensive clinical trials to better understand the full impact of light therapies. The exploration of other light-based treatments, such as LLLT and ILIB, warrants further research to broaden the scope of effective migraine management strategies.

Endovascular Treatment for Spontaneous bilateral carotid artery dissection with acute ischemic stroke: A Case Report with automated postprocessing CT perfusion findings and Review of the Literature.

Carotid artery dissection (CAD) is a common cause of stroke, accounting for up to 25% of all ischemic strokes in young and middle-aged patients. CAD should be considered in young patients with unexplained head and neck pain, with or without focal neurological symptoms and signs. While the clinical features may raise suspicion for CAD, the diagnosis is confirmed by its typical neuroimaging findings. Meanwhile, simultaneous spontaneous dissection of the bilateral carotid artery has rarely been reported. We herein describe a clinically challenging case of a simultaneous bilateral CAD that was successfully treated with bilateral carotid artery stenting (CAS). The patient recovered satisfactorily after completing the whole course of treatment. Keywords: Acute stroke, Bilateral Spontaneous carotid artery dissection, Endovascular treatment.

Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19.

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus-pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.

2022 Taiwan Guidelines for Preventive Treatment of Migraine.

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for migraine prevention in Taiwan. The subcommittee assessed the results of recently published trials, meta-analyses, and guidelines. After expert panel discussions, the subcommittee reached a consensus on the preventive treatment of migraine in Taiwan, which includes recommendation levels, the strength of evidence, and essential prescription information (i.e., dosage and adverse effects) . The recent introduction of CGRP monoclonal antibodies has had a substantial effect on migraine treatment. Thus, the subcommittee updated the previous version of the treatment guideline published in 2017. Preventive medications for migraines can be divided into the following categories: ß-blockers, anticonvulsants, calcium channel blockers, antidepressants, onabotulinumtoxinA, anti-CGRP monoclonal antibodies, and complementary and alternative medicine. For episodic migraine prevention, propranolol, flunarizine, and topiramate are recommended as the first-line medications. Second-line medications for episodic migraine prevention include valproic acid, amitriptyline, and anti-CGRP monoclonal antibodies. Other treatment options could be used as third-line treatments. For chronic migraine prevention, topiramate, flunarizine, onabotulinumtoxinA, and anti-CGRP monoclonal antibodies are recommended as first-line therapies. Preventive medications for episodic migraine can also be used as second-line treatments for chronic migraine. For menstrual migraines, nonsteroidal anti-inflammatory drugs and triptans can be used for short-term prophylaxis. Indications for starting preventive treatment include a headache frequency of ≥4 days per month, profound disabilities, failure of or contraindication to acute therapies, a complicated migraine with debilitating (e.g., hemiplegic) auras, and migrainous brain infarction. The general principle for oral preventives is to "start low and go slow" while monitoring for adverse events and comorbid conditions. Physicians could consider gradually tapering the medications in patients with sustained improvement over 3 to 6 months in episodic migraine and 6 to 12 months in chronic migraine. Education about not overusing acute medications is also essential for all patients with migraine. Key words: migraine, preventive treatment, evidence-based medicine, guidelines, CGRP monoclonal antibodies, onabotulinumtoxinA, neuromodulation.

Prevalence and association of lifestyle and medical-, psychiatric-, and pain-related comorbidities in patients with migraine: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Migraine has been associated with many comorbidities. However, lifestyle factors and the presence of comorbid diseases have not previously been extensively studied in the same sample. This study aimed to compare the prevalence of unhealthy lifestyle factors and comorbid diseases between patients with migraine and migraine-free controls with subgroup analyses to determine the pathophysiology and possible consequences. METHODS: This cross-sectional study recruited 1257 patients with migraine between the ages of 20 and 65 years from a headache outpatient clinic in Taiwan and 496 non-migraine controls. All participants completed questionnaires regarding demographics, migraine diagnosis, sleep, headache burden, and medical, pain, and psychiatric conditions. Participants also underwent a structured interview. The associations between comorbidities and migraine were investigated and further stratified by sex and aura. RESULTS: Patients with migraine with aura had an unhealthier lifestyle compared with controls in the form of current smoking status (15.5% [67/431] vs. 11.5% [57/496], p = 0.013). Furthermore, medical- (e.g., thyroid disease; 7.2% [91/1257 vs. 2.8% [14/496]; p = 0.006), psychiatric- (e.g., depression; 6% [76/1257 vs. 2.6% [13/496]; p = 0.031), and pain-related (e.g., fibromyalgia; 8% [101/1257 vs. 3.2% [16/496]; p = 0.006) comorbidities were more prevalent in patients compared with controls. Subgroup analyses revealed that chronic migraine, migraine with aura, and female sex were associated with a greater number of significant comorbidities than episodic migraine, migraine without aura, and male patients with migraine, respectively. CONCLUSION: Individuals seeking treatment for migraine reported greater levels of smoking and medical, psychiatric, and pain conditions than non-treatment-seeking healthy controls who were recruited from the community. Understanding the relationship between migraine and comorbid diseases may improve medical care as well as the quality of life.

Evidence of Potential Mechanisms of Acupuncture from Functional MRI Data for Migraine Prophylaxis.

PURPOSE OF REVIEW: To summarize the clinical neuroimaging evidence pertaining to the potential mechanisms of acupuncture for migraine prophylaxis. RECENT FINDINGS: From a descriptive perspective, converging evidence from recent neuroimaging studies, mainly from functional MRI (fMRI) studies, has demonstrated that when compared with sham acupuncture, verum acupuncture could normalize the decrease of the functional connectivity of the rostral ventromedial medulla-trigeminocervical complex (RVM/TCC) network, frontal-parietal network, cingulo-opercular networks, and default mode network and could normalize sensorimotor network connectivity with sensory-, affective-, and cognitive-related brain areas. These areas overlap with those of the pain matrix. Verum acupuncture works in a more targeted and unique manner compared with sham acupuncture in patients with migraine. These findings from neuroimaging studies may provide new perspectives on the validation of acupoints specificity and confirm the central modulating effects of acupuncture as a migraine prevention treatment. However, the exact mechanism by which acupuncture works for migraine prophylaxis remains unclear and warrants investigation. Future studies with larger sample sizes are still needed to confirm the current results and to further evaluate the complex and specific effects of acupuncture by analyzing different stimulus conditions, such as verum vs. sham acupuncture, deqi vs. no deqi, different acupuncture points or meridians, and different manipulation methods. Moreover, instead of focusing on the changes in a single area of the brain, researchers should focus more on the relationships among the functional connectivity network of brain areas such as the RVM/TCC, thalamus, anterior cingulate cortex (ACC), superior temporal gyrus (STG), and supplementary motor area (SMA) to explore the underlying mechanism of the effects of acupuncture.

Fasting plasma glucose variability and HbA1c are associated with peripheral artery disease risk in type 2 diabetes.

BACKGROUND: This study investigated whether visit-to-visit fasting plasma glucose (FPG) variability, as measured by the coefficient of variation (CV), increased peripheral artery disease (PAD) risk. METHODS: Individuals with type 2 diabetes from the National Diabetes Care Management Program during the period 2002-2004, ≥ 30 years of age, and free of PAD (n = 30,932) were included and monitored until 2011. Cox proportional hazards regression models were implemented to analyze related determinants of PAD. RESULTS: A total of 894 incident cases of PAD were identified during an average 8.2 years of follow-up, resulting in a crude incidence rate of 3.53 per 1000 person-years. Both FPG-CV and HbA1c were significantly associated with PAD after multivariate adjustment, with corresponding hazard ratios of 1.24 [95% confidence interval (CI) 1.04-1.47] for FPG-CV in the third tertile and 1.50 (95% CI 1.10-2.04) for HbA1c ≥ 10%. The findings of the sensitivity analysis remained consistent after excluding potential confounders, demonstrating the consistency of the results. CONCLUSIONS: The associations between HbA1c, variability in FPG-CV, and PAD suggest a linked pathophysiological mechanism, suggesting the crucial role of glycemic variability in clinical management and therapeutic goals in preventing PAD in type 2 diabetes.

The association between melatonin and episodic migraine: A pilot network meta-analysis of randomized controlled trials to compare the prophylactic effects with exogenous melatonin supplementation and pharmacotherapy.

Although exogenous melatonin supplementation has been suggested to be effective for episodic migraine prophylaxis, there is no conclusive evidence comparing the efficacy of exogenous melatonin supplementation to the other FDA-approved pharmacotherapy for episodic migraine prophylaxis. The aim of the current network meta-analysis (NMA) was to compare the efficacy of exogenous melatonin supplementation in patients with episodic migraine. The randomized placebo-controlled trials or randomized controlled trials (RCTs) incorporating a placebo in the study designs were included in our analyses. All of the NMA procedures were conducted under the frequentist model. The primary outcome was changes in frequency of migraine days and response rate after migraine prophylaxis with melatonin supplementation or pharmacological interventions. We included 25 RCTs in total with 4499 patients (mean age = 36.0 years, mean female proportion = 78.9%). The NMA demonstrated that migraine prophylaxis with oral melatonin 3 mg/d (immediate-release) at bedtime was associated with the greatest improvement in migraine frequency [mean difference = -1.71 days, 95% confidence interval (CI): -3.27 to -0.14 days compared to placebo] and the second highest response rate (odds ratio = 4.19, 95% CI = 1.46 to 12.00 compared to placebo). Furthermore, oral melatonin 3 mg (immediate-release) at bedtime was the most preferred pharmacological intervention among all of the investigated interventions when improvements in migraine frequency, response rate, dropout rate, and rates of any adverse events were taken into account. This pilot NMA suggests the potential prophylactic role of exogenous melatonin supplementation in patients with episodic migraine.

Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice.

Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice. Design and Methods: Male CD1 mice were randomly divided into seven groups, the control Con (4) and Con (8)+saline groups were fed a standard control diet for four or eight weeks; the experimental HFD (4) and HFD (8)+saline groups were fed a high fat diet for four or eight weeks; the HFD (8)+LBNG, HFD (8)+MBNG, and HFD (8)+HBNG groups received a high fat diet along with low, moderate or high doses of BNG-1 (0.026, 0.035, and 0.052g/30g body weight) which was administered for the last four weeks of an eight-week experimental period. After the end of experiment, blood and tissue samples were taken and analyzed. Results: Mice in the HFD (4) group had higher levels of alanine aminotransferase (ALT), plasma and hepatic triglyceride and cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) compared with mice in the Con (4) group. Mice receiving the high fat diet along with the BNG-1 supplement had decreased body weight gains and lower visceral fat weights compared with the HFD (8)+saline group. They had also significantly reduced levels of abnormal ALT and HOMA-IR, and improved blood lipid profile. BNG-1-treated mice exhibited reduced hepatic lipid accumulation, lower oxidative stress, and decreased expression of pro-inflammatory cytokines (TNF-α and IL-1ß). Furthermore, BNG-1 treatment resulted in down-regulation of hepatic cyclic-AMP dependent PDE3B and up-regulation of PDE3B expression in epididymis adipose tissue. Conclusions: BNG-1 mediated changes in PDE3B expression along with reduction in oxidative stress and inflammation. BNG-1 may ameliorate insulin resistance and hepatic steatosis in the NAFLD mouse model.

Association of temporal distribution of fine particulate matter with glucose homeostasis during pregnancy in women of Chiayi City, Taiwan.

BACKGROUND: To investigate the effects of fine particulate matter (PM2.5) on the indicators of glucose homeostasis during pregnancy. METHODS: A total of 3589 non-diabetic pregnant women who underwent a 3-h 100-g oral glucose tolerance test (OGTT) were enrolled from a tertiary teaching hospital in Chiayi City, Taiwan between 2006 and 2014. Fasting, 1-h, 2-h, and 3-h glucose levels after an OGTT were used as indicators of glucose homeostasis. PM2.5 and other air pollution data were obtained from one fixed-site monitoring station (Chiayi City station) operated by Taiwan Environmental Protection Administration (EPA). We used mixed models for indicators of glucose homeostasis to estimate the effects of PM2.5. The models were adjusted for individual-specific effects (nulliparous status, age, body mass index, season, and year) and the moving averages of temperature and relative humidity in the corresponding study period. RESULTS: There were significant relationships between PM2.5 and the glucose homeostasis indicators, including fasting, 1-h, 2-h, and 3-h glucose levels in the single-pollutant covariate-adjusted model. The pre-screening 1-month to 1-year moving averages of IQR increases in PM2.5 were significantly associated with elevated fasting OGTT glucose levels (1.32-5.87mg/dL). The two-pollutant covariate-adjusted models had similar results. CONCLUSIONS: We found positive associations between PM2.5 and OGTT glucose levels during pregnancy. The association was especially pronounced for the fasting and 1-h glucose levels. PM2.5 exposure in the second trimester may enhance this effect. Exposure to PM2.5 was associated with glucose homeostasis during pregnancy.

Sleep in Patients with Chronic Migraine.

PURPOSE OF REVIEW: The biological and pathophysiological interaction between sleep and chronic migraine (CM) remains to be fully elucidated. In this article, we provide a narrative review of the literature on sleep disturbance and CM, highlighting recent advances in sleep research and insights into mechanisms that could mediate a role of sleep disturbances in migraine chronification. We discuss the potential for cognitive-behavioral insomnia therapy (CBTi) as an intervention for CM with comorbid insomnia. Finally, we propose a model of the mechanisms underlying the interactions among sleep physiology, maladaptive migraine-coping behaviors, and coexisting factors which contribute to sleep disturbances in CM based on conceptual models used in sleep research. RECENT FINDINGS: Insomnia is the most common sleep complaint among patients with CM. CM patients experience more frequent and severe insomnia symptoms than patients with episodic migraine (EM). It has been suggested that sleep disturbances may predispose individuals to migraine attacks, which may affect the pain-processing trigeminovascular system and thus play a role in migraine progression. Encouraging but limited evidence suggests that management of insomnia via behavioral sleep therapy may reverse CM to EM and possibly prevent migraine chronification. Migraine has a complex relationship with sleep. The use of objective sleep study such as polysomnographic microstructural sleep analysis and actigraphy could help connect sleep disturbances and processes related to CM. Future longitudinal studies should examine whether effective behavioral treatments such as CBTi can reverse migraine chronification.

Migraine and Risk of Ocular Motor Cranial Nerve Palsies: A Nationwide Cohort Study.

PURPOSE: To determine whether migraine is associated with an increased risk of developing ocular motor cranial nerve palsies (OMCNP). DESIGN: Nationwide retrospective cohort study. PARTICIPANTS: Medical records of patients with migraine who were entered in the National Health Insurance Research Database (NHIRD) between 2005 and 2009 were retrieved from the NHIRD in Taiwan. Two cohorts were selected: patients with migraine (n = 138 907) and propensity score-matched controls (n = 138 907). MAIN OUTCOME MEASURES: Cohorts were followed until the end of 2010, death, or occurrence of cranial nerve (CN)3, CN4, or CN6 palsies. A Cox proportional hazards regression model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), which were used to compare to the risk of developing CN3, CN4, and CN6 palsy between cohorts. RESULTS: After a mean follow-up period of 3.1 years (range, 1-6 years), the migraine cohort exhibited a greater risk of developing subsequent CN3, CN4, and CN6 palsies compared with the control cohort (HR, 2.67, P < 0.001; HR, 4.23, P < 0.001; HR, 3.37; P < 0.001). This finding was maintained after excluding potential confounders during sensitivity tests. Moreover, the significant association between migraine and OMCNP remained after we adjusted for potential risk factors of microvascular ischemia. However, different migraine subtypes showed no significant differences. CONCLUSIONS: Migraine is an unrecognized risk factor for OMCNP development in adults. Further studies are needed to validate our findings and to delineate the exact pathophysiologic mechanisms linking migraine and OMCNP.

Increased Risk of Stroke in Patients with Isolated Third, Fourth, or Sixth Cranial Nerve Palsies: A Nationwide Cohort Study.

BACKGROUND AND PURPOSE: The aim of this nationwide cohort study was to evaluate whether the occurrence of isolated 3rd, 4th or 6th cranial nerve (CN) palsies is associated with a higher risk of ischemic stroke. METHODS: This study utilized data from Taiwan Longitudinal Health Insurance Database during 1995-2012. Subjects aged 20 years or older who had isolated CN 3/4/6 palsies diagnosed by a neurologist or ophthalmologist between January 2000 and December 2011 were included. A set of propensity score matched, randomly sampled patients who had never been diagnosed with CN 3/4/6 palsies were extracted to constitute the control group (cases and controls = 1:4). All subjects were followed until death, loss due to follow-up or completion of the study. Cox proportional hazard regression model stratified by matched pairs was used to estimate the hazards ratio (HR) of ischemic stroke. RESULTS: A total of 657 patients with isolated CN 3/4/6 palsies (61.1% male, mean age 54.8 years) were identified. Compared with control group, the patients with isolated CN 3/4/6 palsies exhibited an increased risk of ischemic stroke (CN3: adjusted HR 3.69 (95% CI 2.20-6.19); CN4: 2.71 (95% CI 1.11-6.64); CN6: 2.15 (95% CI 1.31-3.52)). The association between CN 3/4/6 palsies and ischemic stroke was detected in both separate subgroup and sensitivity analyses. CONCLUSIONS: The patients with CN 3/4/6 palsies exhibited an increased risk of developing ischemic stroke. Therefore, isolated ocular motor nerves palsies appear to represent an unrecognized risk factor for ischemic stroke, and these require further confirmation and exploration.

Visit-to-visit variability of fasting plasma glucose as predictor of ischemic stroke: competing risk analysis in a national cohort of Taiwan Diabetes Study.

BACKGROUND: Glycemic variation as an independent predictor of ischemic stroke in type 2 diabetic patients remains unclear. This study examined visit-to-visit variations in fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), for predicting ischemic stroke independently, regardless of glycated hemoglobin (HbA1c) and other conventional risk factors in such patients. METHODS: Type 2 diabetic patients enrolled in the National Diabetes Care Management Program, ≥30 years old and free of ischemic stroke (n = 28,354) in 2002 to 2004 were included, and related factors were analyzed with extended Cox proportional hazards regression models of competing risk data on stroke incidence. RESULTS: After an average 7.5 years of follow-up, there were 2,250 incident cases of ischemic stroke, giving a crude incidence rate of 10.56/1,000 person-years (11.64 for men, 9.63 for women). After multivariate adjustment, hazard ratios for the second, third and fourth versus first FPG-CV quartile were 1.11 (0.98, 1.25), 1.22 (1.08, 1.38) and 1.27 (1.12, 1.43), respectively, without considering HbA1c, and 1.09 (0.96, 1.23), 1.16 (1.03, 1.31) and 1.17 (1.03, 1.32), respectively, after considering HbA1c. CONCLUSIONS: Besides HbA1c, FPG-CV was a potent predictor of ischemic stroke in type 2 diabetic patients, suggesting that different therapeutic strategies now in use be rated for their potential to (1) minimize glucose fluctuations and (2) reduce HbA1c level in type 2 diabetic patients to prevent ischemic stroke.

Update on gepants for the treatment of chronic migraine.

Chronic migraine (CM) is a profoundly debilitating condition that has detrimental clinical and social outcomes. Over the past two decades, novel small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, known as gepants, and CGRP monoclonal antibodies (mAbs) have been developed, ushering in a new era of migraine-specific treatment. In this review, we discuss the literature investigating the role of gepants for the treatment of CM. Numerous completed and ongoing clinical studies have conclusively demonstrated the safety, tolerability, and efficacy of several gepants for the acute treatment of migraine. However, preventive trials involving gepants have focused on patients with episodic migraine, with atogepant being the only gepant approved for CM prevention by the US Food and Drug Administration at the time of writing. Although some preliminary positive results have been reported, further research is still required to achieve additional advancements in the future. In summary, the effectiveness of gepants for treating individuals with CM are highly expected. This review highlights the development and current progress of gepants for the treatment of CM, focusing both on their role as acute abortive agents and preventive measures and on their concomitant use with other antimigraine medications, such as CGRP mAbs or triptans.

Neuroimmunological effects of omega-3 fatty acids on migraine: a review.

Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.

Association between exposure to particulate matter and incidence of Parkinson's disease: A nationwide cohort study in Taiwan.

Objective: Emerging evidence suggests that air pollution exposure may increase the risk of Parkinson's disease (PD). We aimed to investigate the association between exposure to fine particulate matter (PM2.5) and the risk of incident PD nationwide. Methods: We utilized data from the Taiwan National Health Insurance Research Database, which was spatiotemporally linked with air quality data from the Taiwan Environmental Protection Administration website. The study population consisted of participants who were followed from the index date (January 1st, 2005) until the occurrence of PD or the end of the study period (December 31st, 2017). Participants who had a prior diagnosis of PD before the index date were excluded. To evaluate the association between exposure to PM2.5 and incident PD, we employed a Cox regression to estimate the hazard ratio with a 95% confidence interval (CI). Results: A total of 454,583 participants were included, with a mean (SD) age of 63.1 (9.9) years and a male proportion of 50%. Over a mean follow-up period of 11.1 (3.6) years, 4% of the participants (n = 18,862) developed PD. We observed a significant positive association between PM2.5 exposure and the risk of PD, with a hazard ratio of 1.22 (95% CI, 1.20-1.23) per interquartile range increase in exposure (10.17 µg/m3) when adjusting for both SO2 and NO2. Conclusion: We provide further evidence of an association between PM2.5 exposure and risk of PD. These findings underscore the urgent need for public health policies aimed at reducing ambient air pollution and its potential impact on PD.

High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.

Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.