The Efficacy of Physical Therapy and Rehabilitation Approaches in Chronic Migraine: A Systematic Review and Meta-Analysis.

BACKGROUND: Pharmacological treatment is the primary approach in chronic migraine (CM), although non-drug interventions such as physical therapy are used as adjunct treatments. We aimed to review the efficacy of physical therapy and rehabilitation approaches for CM and their impact on quality of life (QoL) and disability. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included randomized controlled trials (RCTs) in adults with CM. The primary outcomes were changes in intensity, frequency, duration of headache, disability, and QoL. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Data synthesis and quantitative analysis were conducted on relevant studies. RESULTS: Seven RCTs were included in the narrative review, and five of them were eligible for quantitative analysis. Aerobic exercise (AE), osteopathic manipulative treatment (OMT), occipital transcutaneous electrical stimulation (OTES), acupressure, hydrotherapy, instrument-assisted soft tissue mobilization (IASTM), facial proprioceptive neuromuscular facilitation (FPNF), and connective tissue massage (CTM) were used in CM. AE combined with pharmacological therapy reduced the frequency, duration, and intensity of headache. OMT combined with medication improved QoL and reduced disability, intensity of pain, and migraine days per month. Hydrotherapy combined with medication also resulted in improvements in the intensity of headache, frequency, and overall QoL. IASTM and OTES reduced the intensity of headache, alleviated neck pain, and improved QoL, although there were conflicting findings following OTES alone on disability and intensity of headache. Both FPNF and CTM reduced the intensity of headache. Acupressure as an adjunct to medication did not show additional benefits on the intensity of headache and QoL. Quantitative analysis of the data showed that manual physical therapy combined with medication reduced the intensity of headache (p = 0.0796), and manual or AE combined with medication reduced the headache days per month (p = 0.047). CONCLUSIONS: A limited number of RCTs investigating the efficacy of physical therapy and rehabilitation approaches show promise in improving headache symptoms, reducing disability, and enhancing QoL in CM. Meta-analysis of the data also supported favorable outcomes for both intensity and headache days per month. Further research is needed to better understand the efficacy, optimal duration, and safety of physical therapy and rehabilitation approaches for CM, and to explore alternative interventions.

Antiseizure medications as migraine preventatives: a call for action for a teratogenic and neurodevelopmental risk removal.

INTRODUCTION: A recent study has demonstrated an increased risk of neurodevelopmental disorders, including autism spectrum disorder, in individuals exposed to either valproate or topiramate monotherapy. Regulatory bodies have initiated a review to reassess the safety of topiramate exposure during pregnancy. These novel findings raise concerns regarding the recommendation of antiseizure medications in women of childbearing potential. This manuscript highlights current research defining concerns specific to the use of valproate and topiramate in women of childbearing potential. AREAS COVERED: This manuscript summarizes recent findings regarding the safety of valproate and topiramate when compared to alternative therapies for the preventative treatment of migraine in women of childbearing potential. The studies included in this review were selected following a comprehensive literature review of multiple relevant databases. All studies that were published within the past 15 years were considered for inclusion. EXPERT OPINION: The use of valproate and topiramate in women of childbearing potential should be highly discouraged. Our recommendations include a review of current prescribing guidelines, further public education regarding the neurodevelopmental and congenital risks associated with the use of valproate and topiramate, and an appeal for further research defining the safety of alternative medications for migraine prevention when intrauterine exposure is possible.

A Pilot Study on the Association of Lead, 8-Hydroxyguanine, and Malondialdehyde Levels in Opium Addicts' Blood Serum with Illicit Drug Use and Non-Addict Persons.

While a large body of literature has shown the health problems of illicit drug use, research is needed on how substance abuse impacts DNA damage and contaminants in blood, especially given Pb-contaminated opium. This pilot study aimed to evaluate the levels of lead (Pb), 8-hydroxy di-guanine (8-oxo-Gua), and malondialdehyde (MDA) in the blood serum of opium addicts and non-addict people. The current study is a case-control study with a cross-sectional design. A sample of 50 opium-addicted and non-addict adults were chosen for this study using convenience and random sampling methods. Participants were divided into two groups: addicts and non-addicts. The atomic absorption spectroscopy method was used to measure the quantity of Pb, and the Enzyme-Linked Immunosorbent Assay (ELISA) method was used to measure the amount of 8-oxo-Gua and MDA. The data were analyzed using an independent t-test. The results show that the amount of Pb in the blood serum of addicted women and men was higher than levels in non-addict men and women, for the study participants (p-value = 0.001). Blood levels were not significantly different between addicts and non-addicts for men or women for 8-oxo-Gua (p-value = 0.647 for women and p-value = 0.785 for men) and MDA (p-value = 0.867 for women and p-value = 0.995 for men). In general, addicts' blood Pb levels were found to be substantially higher than those of normal non-addict persons in this pilot study. As a result, testing for blood Pb levels in addicts may be informative in instances when symptoms are inconclusive.

Recent advancements in tension-type headache: a narrative review.

INTRODUCTION: Tension-type headache (TTH) is the most common primary headache disorder with a prevalence of up to 78% in general population and huge expenses in terms of health service. Despite its high incidence and impact on life's quality the knowledge on the pathophysiology and efficacious treatment of TTH was still limited. AREAS COVERED: In recent years, a series of studies highlighted the heterogeneous nature of this pathology that seems to be determined by a complex interaction between genetic, environmental, and neuromuscular factors, which result in nociceptive system activation. In this setting, alongside the simple analgesic therapies used during the acute attack, a series of therapeutic options based on newly acquired experiences have taken hold. EXPERT REVIEW: Not having a single substrate or a typical site of pathophysiology, TTH must be analyzed in a global and multidisciplinary way. Herein, we perform a narrative review of the most recent advancement stimulating the concept of this disease as the tip of the iceberg of a more complex individual malaise secondary to different alterations. Strategies based solely on symptomatic drugs should therefore be avoided by experienced personnel and treatment should aim at taking charge of the patient considering the processes behind this complex pathology.

Non-Pharmacological Approaches to Headaches: Non-Invasive Neuromodulation, Nutraceuticals, and Behavioral Approaches.

Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.

Gut-brain Axis and migraine headache: a comprehensive review.

The terminology "gut-brain axis "points out a bidirectional relationship between the GI system and the central nervous system (CNS). To date, several researches have shown that migraine is associated with some gastrointestinal (GI) disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). The present review article aims to discuss the direct and indirect evidence suggesting relationships between migraine and the gut-brain axis. However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. Studies suggest that this interaction seems to be influenced by multiple factors such as inflammatory mediators (IL-1ß, IL-6, IL-8, and TNF-α), gut microbiota profile, neuropeptides and serotonin pathway, stress hormones and nutritional substances. Neuropeptides including CGRP, SP, VIP, NPY are thought to have antimicrobial impact on a variety of the gut bacterial strains and thus speculated to be involved in the bidirectional relationship between the gut and the brain. According to the current knowledge, migraine headache in patients harboring HP might be improved following the bacteria eradication. Migraineurs with long headache history and high headache frequency have a higher chance of being diagnosed with IBS. IBS and migraine share some similarities and can alter gut microflora composition and thereby may affect the gut-brain axis and inflammatory status. Migraine has been also associated with CD and the condition should be searched particularly in patients with migraine with occipital and parieto-occipital calcification at brain neuroimaging. In those patients, gluten-free diet can also be effective in reducing migraine frequency. It has also been proposed that migraine may be improved by dietary approaches with beneficial effects on gut microbiota and gut-brain axis including appropriate consumption of fiber per day, adhering to a low glycemic index diet, supplementation with vitamin D, omega-3 and probiotics as well as weight loss dietary plans for overweight and obese patients.

Association of diet and headache.

The global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.

Neuromodulation of chronic headaches: position statement from the European Headache Federation.

The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases. Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches. In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile.

A six year retrospective review of occipital nerve stimulation practice--controversies and challenges of an emerging technique for treating refractory headache syndromes.

BACKGROUND: A retrospective review of patients treated with Occipital Nerve Stimulation (ONS) at two large tertiary referral centres has been audited in order to optimise future treatment pathways. METHODS: Patient's medical records were retrospectively reviewed, and each patient was contacted by a trained headache expert to confirm clinical diagnosis and system efficacy. Results were compared to reported outcomes in current literature on ONS for primary headaches. RESULTS: Twenty-five patients underwent a trial of ONS between January 2007 and December 2012, and 23 patients went on to have permanent implantation of ONS. All 23 patients reached one-year follow/up, and 14 of them (61%) exceeded two years of follow-up. Seventeen of the 23 had refractory chronic migraine (rCM), and 3 refractory occipital neuralgia (ON). 11 of the 19 rCM patients had been referred with an incorrect headache diagnosis. Nine of the rCM patients (53%) reported 50% or more reduction in headache pain intensity and or frequency at long term follow-up (11-77 months). All 3 ON patients reported more than 50% reduction in pain intensity and/or frequency at 28-31 months. Ten (43%) subjects underwent surgical revision after an average of 11 ± 7 months from permanent implantation - in 90% of cases due to lead problems. Seven patients attended a specifically designed, multi-disciplinary, two-week pre-implant programme and showed improved scores across all measured psychological and functional parameters independent of response to subsequent ONS. CONCLUSIONS: Our retrospective review: 1) confirms the long-term ONS success rate in refractory chronic headaches, consistent with previously published studies; 2) suggests that some headaches types may respond better to ONS than others (ON vs CM); 3) calls into question the role of trial stimulation in ONS; 4) confirms the high rate of complications related to the equipment not originally designed for ONS; 5) emphasises the need for specialist multidisciplinary care in these patients.

Cervicogenic headache: practical approaches to therapy.

Cervicogenic headache is a relatively common and still controversial form of headache arising from structures in the neck. The estimated prevalence of the disorder varies considerably, ranging from 0.7% to 13.8%. Cervicogenic headache is a 'side-locked' or unilateral fixed headache characterised by a non-throbbing pain that starts in the neck and spreads to the ipsilateral oculo-fronto-temporal area. In patients with this disorder, attacks or chronic fluctuating periods of neck/head pain may be provoked/worsened by sustained neck movements or stimulation of ipsilateral tender points. The pathophysiology of cervicogenic headache probably depends on the effects of various local pain-producing or eliciting factors, such as intervertebral dysfunction, cytokines and nitric oxide. Frequent coexistence of a history of head traumas suggests these also play an important role. A reliable diagnosis of cervicogenic headache can be made based on the criteria established in 1998 by the Cervicogenic Headache International Study Group. Positive response after an appropriate nerve block is an essential diagnostic feature of the disorder. Differential diagnoses of cervicogenic headache include hemicrania continua, chronic paroxysmal hemicrania, occipital neuralgia, migraine and tension headache. Various therapies have been used in the management of cervicogenic headache. These range from lowly invasive, drug-based therapies to highly invasive, surgical-based therapies. This review evaluates use of drug therapy with paracetamol and NSAIDs, infliximab and botulinum toxin type A; manual modalities and transcutaneous electrical nerve stimulation therapy; local injection of anaesthetic or corticosteroids; and invasive surgical therapies for the treatment of cervicogenic headache. A curative therapy for cervicogenic headache will not be developed until increased knowledge of the aetiology and pathophysiology of the condition becomes available. In the meantime, limited evidence suggests that therapy with repeated injections of botulinum toxin type A may be the most safe and efficacious approach. The surgical approach, which includes decompression and radiofrequency lesions of the involved nerve structures, may also provide physicians with further options for refractory cervicogenic headache patients. Unfortunately, the paucity of experimental models for cervicogenic headache and the relative lack of biomolecular markers for the condition mean much is still unclear about cervicogenic headache and the disorder remains inadequately treated.