Nutraceuticals in migraine.

Nutraceuticals represent substances derived from food or plants that provide medical or health benefits, and are increasingly sought by patients as a means of treating migraine in a natural, effective, and safe manner as conventional therapies often fail, are expensive, and laden with side effects. This chapter reviews various nutraceutical therapies for migraine including phytomedicines (plant-based therapies), diets for migraine management and vitamin, mineral, and supplement-based treatments for migraine with respect to preclinical and clinical evidence. Reviewed herein are a multitude of nutraceutical options for the treatment of migraine including vitamins (e.g., riboflavin), antioxidants, and plants/phytomedicines: feverfew, butterbur, cannabis, St. John's Wort, Rosa x damascena, and Gingko biloba. Dietary interventions for migraine include low lipid, vegan, ketogenic, and DASH (dietary approaches to stop hypertension). Supplements such as polyunsaturated fatty acids (PUFAs) as well as l-carnitine, pre/probiotics, and melatonin are also discussed. Migraine patients and their caregivers have an armamentarium of nutraceutical options to treat headache. While some therapies such as vitamins harbor stronger evidence with more rigorous studies, patients may also choose dietary therapies that may offer more systemic health benefits while also improving migraine. As cannabis legalization spreads worldwide, care providers must be aware of the limited evidence in migraine. Future studies may explore traditional ancient medicines for migraine at basic science and clinical level, while currently adopted and new nutraceutical treatments may benefit from partnership with industry to engage in larger trials in humans.

Nutraceuticals and Behavioral Therapy for Headache.

PURPOSE OF REVIEW: Headache affects and disables at least 1 billion people worldwide. Patients and providers seek new therapies to relieve headache without the side effects and financial burden of current treatments. This narrative review highlights recent treatment advances in integrative headache medicine: nutraceuticals and behavioral therapies. RECENT FINDINGS: Growing use of complementary and alternative medicine (CAM) therapies for headache (riboflavin, coenzyme Q10, magnesium, vitamin D, melatonin) alongside mainstream treatments is increasing with improving evidence of quality, safety, and tolerability. Increasing interest in medical cannabis is tempered by lack of evidence regarding safety and efficacy. Behavioral therapies including cognitive behavioral therapy (CBT), biofeedback, mindfulness-based stress reduction (MBSR), and acceptance and commitment therapy (ACT) improve patient resiliency and self-efficacy outcomes and reduce disability. The body of evidence for nutraceutical and behavioral CAM interventions for headache continues to grow and improve in quality. Providers and patients should educate themselves regarding CAM therapies as part of integrative headache management. Future studies should examine combinatorial trials of CAM therapies against current standards of headache care.

Diffusion Imaging of Cerebral Diaschisis in Neonatal Arterial Ischemic Stroke.

BACKGROUND: Neonatal arterial ischemic stroke is a leading cause of cerebral palsy and lifelong disability. Diffusion-weighted imaging has revolutionized diagnosis and facilitated outcome prognostication in acute neonatal arterial ischemic stroke. Diaschisis refers to changes in brain areas functionally connected but structurally remote from primary injury. We hypothesized that acute diffusion-weighted imaging can quantify cerebral diaschisis and is associated with outcome from neonatal arterial ischemic stroke. METHODS: Subjects were identified from a prospective, population-based research cohort (Alberta Perinatal Stroke Project). Inclusion criteria were unilateral middle cerebral artery neonatal arterial ischemic stroke, diffusion-weighted magnetic resonance imaging within 10 days of birth, and more than 12-months follow-up (pediatric stroke outcome measure). Diaschisis was characterized and quantified using a validated software method (ImageJ). Volumetric analysis assessed atrophy of affected structures. Diaschisis scores were corrected for infarct size and compared with outcomes (Mann-Whitney). RESULTS: From 20 eligible neonatal arterial ischemic strokes, two were excluded for poor image quality. Of 18 remaining (61% male, median age 3.2 days), 16 (89%) demonstrated diaschisis. Thalamus (88%) was the most common location in addition to corpus callosum (50%). Age at imaging was not associated with diaschisis. Affected structures demonstrated atrophy on imaging. Long-term outcomes available in 81% (median age 7.5 years) were not associated with diaschisis scores. CONCLUSIONS: Cerebral diaschisis occurs in neonatal arterial ischemic stroke and can be quantified with diffusion-weighted imaging. Occurrence is common and should not be mistaken for additional infarction. Determining clinical significance will require larger samples with well-characterized long-term outcomes.

Phytomedicines in the Treatment of Migraine.

Migraine is a disabling neurovascular disorder with few targeted, tolerable and effective treatments. Phytomedicines, or plant-based medicinal formulations, hold great promise in the identification of novel therapeutic targets in migraine. Many patients also turn toward herbal and plant-based therapies for the treatment of their migraines as clinical and preclinical evidence of efficacy increases. Patients seek effective and tolerable treatments instead of or in addition to current conventional pharmacologic therapies. We review some phytomedicines potentially useful for migraine treatment-feverfew (Tanacetum parthenium), butterbur (Petasites hybridus), marijuana (Cannabis spp.), Saint John's Wort (Hypericum perforatum) and the Damask rose (Rosa × damascena)-with respect to their mechanisms of action and evidence for treatment of migraine. The evidence for feverfew is mixed; butterbur is effective with potential risks of hepatotoxicity related to preparation; marijuana has not been shown to be effective in migraine treatment, and data are scant; Saint John's Wort shows relevant physiological activity but is a hepatic enzyme inducer and lacks clinical studies for this purpose; the Damask rose when used in topical preparations did not show efficacy in one clinical trial. Other plant preparations have been considered for migraine treatment but most without blinded randomized, placebo-controlled trial evidence.

Nutraceuticals in Migraine: A Summary of Existing Guidelines for Use.

BACKGROUND: The use of nutraceuticals or food/herbal products for health benefits is expanding in adults with migraine as they seek relief from pain in an effective and tolerable manner not always afforded by current conventional pharmacologic therapies. Guidelines from the American Academy of Neurology/American Headache Society, Canadian Headache Society, and European Federation of Neurological Societies have discussed nutraceuticals in varying degrees of detail with at times conflicting recommendations. CONCLUSION: This review serves to provide a summary of existing guidelines for the use of certain nutraceuticals including riboflavin, coenzyme Q10, magnesium, butterbur, feverfew, and omega-3 polyunsaturated fatty acids. The review will also discuss the regulation of nutraceuticals in North America and the current controversy regarding butterbur and its safety.

Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis.

BACKGROUND: Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply leads to a decrease in spina bifida (a birth defect of the spine). Still, many countries around the world have yet to approve mandatory fortification through government legislation. OBJECTIVES: We sought to perform a systematic review and meta-analysis of period prevalence of spina bifida by folic acid fortification status, geographic region, and study population. SEARCH METHODS: An expert research librarian used terms related to neural tube defects and epidemiology from primary research from 1985 to 2010 to search in EMBASE and MEDLINE. We searched the reference lists of included articles and key review articles identified by experts. SELECTION CRITERIA: Inclusion criteria included studies in English or French reporting on prevalence published between January 1985 and December 2010 that (1) were primary research, (2) were population-based, and (3) reported a point or period prevalence estimate of spina bifida (i.e., prevalence estimate with confidence intervals or case numerator and population denominator). Two independent reviewers screened titles and abstracts for eligible articles, then 2 authors screened full texts in duplicate for final inclusion. Disagreements were resolved through consensus or a third party. DATA COLLECTION AND ANALYSIS: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, abstracting data related to case ascertainment, study population, folic acid fortification status, geographic region, and prevalence estimate independently and in duplicate. We extracted overall data and any subgroups reported by age, gender, time period, or type of spina bifida. We classified each period prevalence estimate as "mandatory" or "voluntary" folic acid fortification according to each country's folic acid fortification status at the time data were collected (as determined by a well-recognized fortification monitoring body, Food Fortification Initiative). We determined study quality on the basis of sample representativeness, standardization of data collection and birth defect assessment, and statistical analyses. We analyzed study-level period prevalence estimates by using a random effects model (α level of < 0.05) for all meta-analyses. We stratified pooled period prevalence estimates by birth population, fortification status, and continent. RESULTS: Of 4078 studies identified, we included 179 studies in the systematic review and 123 in a meta-analysis. In studies of live births (LBs) alone, period prevalences of spina bifida were (1) lower in geographical regions with mandatory (33.86 per 100,000 LBs) versus voluntary (48.35 per 100,000 LBs) folic acid fortification, and (2) lower in studies of LBs, stillbirths, and terminations of pregnancy in regions with mandatory (35.22 per 100,000 LBs) versus voluntary (52.29 per 100,000 LBs) fortification. In LBs, stillbirths, and terminations of pregnancy studies, the lowest pooled prevalence estimate was in North America (38.70 per 100,000). Case ascertainment, surveillance methods, and reporting varied across these population-based studies. CONCLUSIONS: Mandatory legislation enforcing folic acid fortification of the food supply lags behind the evidence, particularly in Asian and European countries. This extensive literature review shows that spina bifida is significantly more common in world regions without government legislation regulating full-coverage folic acid fortification of the food supply (i.e., Asia, Europe) and that mandatory folic acid fortification resulted in a lower prevalence of spina bifida regardless of the type of birth cohort. African data were scarce, but needed, as many African nations are beginning to adopt folic acid legislation.