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1.

Purpose of Review

Since up to 40.9% of reproductive aged women have migraine—and reproductive-aged women often reproduce—it is essential that we have good information and guidelines regarding proper treatment of migraine during pregnancy and lactation.

Recent Findings

A review of articles published in the last year on the treatment of migraine during pregnancy and lactation found dishearteningly little. Nevertheless, this article will review the risk/safety information related to migraine treatment in both pregnancy and lactation, citing both new and less recent publications.

Summary

There is little if any formal research is being carried out on pharmacotherapy for migraine that occurs during pregnancy or lactation. This is likely due to two issues: (1) neurology offers little training in female sex hormones, while gynecology is a surgical field; (2) there is the ever-present concern of litigation if any bad outcome occurs, yet there is no designation of “legally safe” that can be applied to a drug’s use in pregnancy and lactation.
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2.

Purpose of Review

The purpose of this review is to evaluate and describe recent and emerging treatment options for episodic migraine.

Recent Findings

Recent advances have been made in better understanding the pathophysiology of migraine, which has led to further investigation of potential new pharmacologic and non-pharmacologic treatment options.

Summary

A number of new medications are emerging for the acute and preventive treatment of migraine, including CGRP monoclonal antibodies, CGRP receptor antagonists, serotonin 5-HT1F agonists, and PACAP receptor monoclonal antibodies. Additionally, newer studies on existing non-invasive neuromodulation devices including transcranial magnetic stimulation, supraorbital transcutaneous nerve stimulation, and transcutaneous vagus nerve stimulation have recently received FDA approval for use in migraine. Neuromodulation devices including percutaneous mastoid electrical stimulation, non-painful remote electrical stimulation, and caloric vestibular stimulation are undergoing further investigation and have shown promising results thus far. These new developments are expected to contribute to better treatment and decreased disability in migraine.
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3.

Purpose of Review

The purpose of this review is to examine the relationship between headaches and epilepsy as well as headaches and psychogenic non-epileptic seizures (PNES). Emphasis was placed on clinical characteristics, pathophysiology, and treatment.

Recent Findings

Epilepsy and headaches are common disorders that co-occur more often than would be expected by chance. There are some overlapping clinical features between migraine and epilepsy as well as evidence for shared underlying mechanisms. Proposed theories for a shared etiology include ion channel dysfunction, glutamatergic mechanisms, and mitochondrial dysfunction. Some, but not all, recent diagnostic classification systems have recognized the relationship between headaches and epilepsy. Ictal headaches are rare and should raise suspicion for PNES. Headaches in patients with epilepsy are undertreated despite evidence for efficacy of abortive headache medications.

Summary

Comorbid headaches and epilepsy are relatively common in the population presenting to a neurologist. Patients who have headaches and epilepsy and/or PNES should receive appropriate treatment that often includes mutually beneficial preventative therapy and includes abortive headache treatment.
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4.

Purpose of Review

Chronic migraine (CM) is a recalcitrant subtype of migraine which causes high degrees of disability, poor treatment responses, and frequent recurrences in sufferers. However, the pathophysiological mechanisms underlying the development and chronification of migraine attacks remain incompletely understood. A validated animal model could help to decipher the pathogenic mechanism of the disease, facilitating the development of possible therapeutic strategies for CM. In this review, we aimed to summarize current animal models of CM and discuss the validity of these models.

Recent Findings

Several methods have been available to induce recurrent headache-like behaviors or biochemical changes in rodents, including repeated dural application of inflammatory soup, chronic systemic infusion of nitroglycerin, repeated administration of acute migraine abortive treatment to simulate medication overuse headache, or genetic modification. These models exhibit some features that are believed to be associated with migraine; however, none of the model can recapitulate all the clinical phenotypes found in humans and each has its own weakness.

Summary

The complex features of CM increase the difficulty of constructing a proper animal model. Nonetheless, currently available models are valid to certain degrees. Future directions might consider simulating the spontaneity and chronicity of migraine by combining known genetic substrates and allostatic loads into the same model.
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5.

Purpose of Review

In this short review, the most common non-invasive neuromodulatory techniques will be described, along with their advantages and disadvantages and their application in headache. Available preventive treatments can be unhelpful or may have unpleasant side effects; moreover, the rate of response to preventive drugs does not exceed 50%, lower in chronic migraine; alternative options would be welcome. Though the concept of neuromodulation was originally developed with invasive methods, newer non-invasive techniques are appearing.

Recent Findings

The novel neuromodulatory techniques have been developed with encouraging results: compared with traditional pharmacotherapy, advantages of non-invasive neuromodulation include reduced incidence of adverse effects, improved adherence, and safety and ease of use. The results are encouraging for acute or preventive treatment of different kinds of headache.

Summary

A variety of neuromodulatory approaches is expanding fastly and has opened new possibilities for treatment of patients suffering from many forms of headache, especially those who have failed traditional pharmacotherapy. The non-invasive treatments can be seen as supplementing traditional management in refractory patients. Current study results are encouraging but preliminary and larger and more rigorous trials are needed to clarify benefit and mode of action.
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6.

Purpose of Review

Episodic migraine is common. Everyday behavioral patterns are associated with migraine attacks and disability. This paper reviews health behaviors that can be targeted in people with episodic migraine to enhance migraine-related outcomes.

Recent Findings

Stressful events and perceived stress have demonstrated associations with migraine attack onset among people with episodic migraine. Consistency in daily patterns (eating, sleeping, exercise, and hydration status) is also associated with migraine activity. Sleep deprivation, fatigue, and poor quality sleep have demonstrated relationships with migraine attack onset, as well as headache frequency and headache-related disability in people with episodic migraine.

Summary

The health behaviors implicated in episodic migraine are part of everyday patterns and can be targeted routinely in clinical practice to improve migraine management. Behavior change is challenging and should ideally be supported by a multidisciplinary team. Future research should focus on evaluating specific behavior change interventions and the relative impact of behavior on migraine outcomes in high- and low-frequency episodic migraine.
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7.

Purpose of Review

Vasoactive peptides play a key role in the attack-initiating cascade of migraine. Recent studies have highlighted a potentially important role for endothelin-1, a potent vasoconstrictor peptide, in migraine pathophysiology. Here, we review the current data on endothelin’s involvement in migraine.

Recent Findings

We identified 23 articles. Nine studies reported on endothelin-1 plasma concentrations in patients with migraine, eight studies investigated relevant genetic associations, five studies investigated endothelin-1 and spreading depression in animals, and one randomized controlled clinical trial tested the efficacy of an endothelin antagonist in the acute treatment of migraine in patients both with and without aura. Elevated endothelin-1 plasma levels have been reported in the early phase of migraine attacks. Genetic abnormalities related to the endothelin type A receptor have been reported in migraineurs. Endothelin-1 potently induces spreading depression in animals, which may explain the connection between endothelial irritation and migraine aura.

Summary

Endothelin-1 could be a primary factor in the attack-triggering cascade of migraine attacks with and without aura. Additional studies in humans and animal models are needed to further elucidate the role of endothelin-1 in migraine.
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8.

Purpose of Review

Symptoms of autonomic dysfunction are common in patients with migraine, both during and between migraine attacks. Studies evaluating objective autonomic testing in patients have found significant, though somewhat conflicting results. The purposes of this review are to summarize and interpret the key findings of these studies, including those evaluating heart rate variability, autonomic reflex testing, and functional imaging in patients with migraine. The neuroanatomy of the central autonomic network as it relates to migraine is also reviewed.

Recent Findings

Several studies have evaluated autonomic balance in migraineurs, with conflicting results on the magnitude of sympathetic versus parasympathetic dysfunction. Most studies demonstrate sympathetic impairment, with a lesser degree of parasympathetic impairment.

Summary

Three trends have emerged: (1) migraine with aura tends to produce more significant autonomic dysfunction than migraine without aura, (2) sympathetic impairment is more common than parasympathetic impairment, and (3) sympathetic impairment is common in the interictal period, with increased sympathetic responsiveness during the ictal period, suggesting adrenoreceptor hypersensitivity.
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9.

Purpose of Review

This review evaluates and explains our current understanding of a rare subtype of migraine, typical aura without headache, also known as migraine aura without headache or acephalgic migraine.

Recent Findings

Typical aura without headache is a known entity within the spectrum of migraine. Its pathophysiology is suggested to be similar to classic migraines, with cortical spreading depression leading to aura formation but without an associated headache. No clinical trials have been performed to evaluate treatment options, but case reports suggest that most patients will respond to the traditional treatments for migraine with aura. Bilateral greater occipital nerve blocks may be helpful in aborting migraine with prolonged aura. Transcranial magnetic stimulation has shown efficacy in aborting attacks of migraine with aura but has not been specifically tested in isolated aura.

Summary

Typical aura without headache occurs exclusively in 4% patients with migraine, and may take place at some point in 38% of patients with migraine with aura. Typical aura without headache commonly presents with visual aura without headache, brainstem aura without headache, and can also develop later in life, known as late-onset migraine accompaniment.
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10.

Purpose of Review

Recurrent painful ophthalmoplegic neuropathy (RPON), formerly known as ophthalmoplegic migraine, is an uncommon disorder with repeated episodes of ocular cranial nerve neuropathy associated with ipsilateral headache. This review discusses the clinical presentation, current understanding of the pathophysiology, key differential diagnoses, and evaluation and treatment of RPON.

Recent Findings

The literature is limited due to the rarity of the disorder. Recent case reports and series continue to suggest the age of first attack is most often during childhood or adolescence as well as a female predominance. Multiple recent case reports and series demonstrate focal enhancement of the affected cranial nerve, as the nerve root exits the brainstem. This finding contributed to the current classification of the disorder as a neuropathy, with the present understanding that it is due to a relapsing-remitting inflammatory or demyelinating process. The link to migraine remains a cause of disagreement in the literature.

Summary

RPON is a complex disorder with features of inflammatory neuropathy and an unclear association with migraine. Regardless, the overall prognosis is good for individual episodes, but permanent nerve damage may accumulate with repeated attacks. A better understanding of the pathogenesis is needed to clarify whether it truly represents a single disorder and to guide its treatment. Until that time, a combined approach with acute and preventive therapies can mitigate acute symptoms as well as attempt to limit recurrence of this disabling syndrome.
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11.

Purpose of Review

This article reviews the recent research and development of electronic health (eHealth) and, in particular, mobile health (mHealth) strategies to deliver behavioral treatment for migraine. Prospects for future development and research of mobile health in migraine are suggested.

Recent Findings

Advances in digital technology and mobile technology have led to an era where electronic and mobile approaches are applied to several aspects of healthcare. Electronic behavioral interventions for migraine seem to be acceptable and feasible, but efficacy measures are uncertain. Clinical trials on mHealth-based classical behavioral therapies, such as relaxation, biofeedback, and cognitive behavioral therapy are missing in the literature. Within mHealth, headache diaries are the most researched and scientifically developed. Still, there is a gap between commercially available apps and scientifically validated and developed apps.

Summary

Digital technology and mobile health has not yet lived out its potential in behavioral migraine therapy. Application of proper usability and functionality designs towards the right market, together with appraisal of medical and technological recommendations, may facilitate rapid development of eHealth and mHealth, while also establishing scientific evidence.
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12.

Purpose of Review

Cyclic vomiting syndrome (CVS) is a misrecognized and probably underdiagnosed episodic syndrome associated with migraine, occurring preferentially in childhood. Attacks are stereotyped for each individual, with predictable periodicity. This review summarizes recent clinical and paraclinical observations in this syndrome, and current approaches in explorations and therapeutics.

Recent Findings

Clinical phenotype during prodromal, vomiting, and recovery phases contains visceral and neuropsychological symptoms, but also cranial and systemic symptoms. Some clinical arguments as circadian or circannual periodicity suggest a chronobiological disease. Red flags in clinical presentation are proposed to distinguish other etiologies of recurrent gastrointestinal disturbances and guide paraclinical explorations. Functional magnetic resonance imaging in both CVS and migraine displayed diminished insular connectivity with the sensorimotor network, suggesting a common pathophysiology.

Summary

Pathophysiology of CVS is not well defined, and there is probably a multifactorial origin. Distinction with other differential diagnoses is a challenge for clinicians. Further research, in particular with functional imaging, are required to define pathophysiology of CVS. Control trials are missing in pediatric population. Injectable or intranasal sumatriptan are often effective. For prophylaxis, amitriptyline, cyproheptadine, or propranolol are the most common treatments, depending on age and comorbidities. Non-pharmacologic measures as lifestyle modification also seem to be effective as preventive treatment.
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13.

Purpose of Review

CGRP is a key neuropeptide in migraine pathophysiology. The blockade of the CGRP pathway at the side of the CGRP receptor of the CGRP peptide leads to the interruption of trigeminal nerve system-mediated headache syndromes such as migraine. Monoclonal antibodies (mAbs) targeting the CGRP pathway have been developed and are currently under investigation for episodic (EM) and chronic migraine (CM) prevention. Here, we report data from these clinical trials.

Recent Findings

Placebo-controlled, randomized double-blind phase studies of CGRP mAbs in episodic and chronic migraine have shown that the specific blockade of the peptide or the CGRP receptor are both powerful mechanisms to reduce migraine frequency. Along with the reduction of acute migraine-specific medication intake, early onset of efficacy of mAbs has been demonstrated. Most common adverse events are injection sider reactions. Depending on the mAb, the administration mode is a monthly or even less frequently s.c. or I.V. formulation.

Summary

Phase II studies in EM and CM demonstrate that CGRP mAbs are effective anti-migraine preventatives with a beneficial adverse event profile. Further detailed results from larger phase III clinical trials are expected soon.
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14.

Purpose of review

The goal of this review is to provide an actualized overview on vestibular migraine in childhood and adolescence, with focus on the epidemiology and clinical presentation as well as its treatment.

Recent findings

Vertigo spells in childhood can evolve into other periodic syndromes and/or migraine types and persist even into adulthood.

Summary

Vestibular migraine (VM) and benign paroxysmal vertigo are the most common causes of vertigo in children and adolescents. The diagnostic criteria for VM are dizziness and vertigo, headache, phonophobia and photophobia, and visual aura. The prevention of attacks is the treatment for children and adolescents with VM, as is recommended for migraine with or without aura. Thus, non-pharmacological measures are the first-line option; when these measures fail or daily activities are notably affected, drugs are administrated. Psychological assessment and cognitive behavioral therapy are also important therapeutic measures in this patient group. There is still insufficient research on VM in children and adolescents; future studies on clinical presentation, evolvement, and specific treatment are necessary.
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15.

Purpose of the Review

The goals of this review are to evaluate recent studies regarding comorbidity between migraine and different metabolic and endocrine disorders and to discuss the role of insulin resistance as a common pathogenetic mechanism of these diseases.

Recent Findings

Recently, several studies showed that migraine is associated with insulin resistance, a condition in which a normal amount of insulin induces a suboptimal physiological response. All the clinical studies that used the oral glucose tolerance test to examine insulin sensitivity found that, after glucose load, there is in migraine patients a significant increase of both plasmatic insulin and glucose concentrations in comparison with controls. On the contrary, no association was found between migraine and type 2 diabetes, while type 1 diabetes seems to have a protective effect in the disease. Obesity and hypertension were shown to be risk factors for both episodic and chronic migraine. Metabolic syndrome has been recently associated mainly with migraine with aura and is now considered a risk factor also for medication overuse headache. Finally, a bidirectional association between migraine and hypothyroidism has been recently demonstrated, suggesting that common genetic or autoimmune mechanisms underlie both diseases.

Summary

Recent studies showed that insulin receptor signaling and the related physiological responses are altered in migraine and may have a relevant pathogenic role in the disease. Further studies are warranted in order to better elucidate mechanisms underlying insulin resistance in migraine in order to develop new therapeutic strategies for this debilitating disease.
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16.

Purpose of Review

Premonitory symptoms in migraine; symptoms occurring before the onset of migraine pain or aura, are an increasingly recognised area of interest within headache research. It has been recently documented in the literature that these symptoms also occur in children and adolescents, with a comparable phenotype to adults. This review discusses the wide presentation of premonitory symptoms in migraine in children and adolescents, and the importance of understanding how these early symptoms are mediated in order to ensure that targeted abortive therapies are developed in the future. Recognition of these symptoms by parents, guardians, teachers and carers is of importance in ensuring early and effective attack treatment.

Recent Findings

A previous clinic-based questionnaire study in 103 children found a prevalence of premonitory symptoms in paediatric migraine of 67%, with a mean number of reported symptoms of two. A recent study found that in a clinic population of 100 children or adolescents with a migraine diagnosis who were preselected as having at least one premonitory symptom associated with their attacks, two or more premonitory symptoms were reported by 85% of patients. The most common symptoms were fatigue, mood change and neck stiffness.

Summary

Although the population prevalence of premonitory symptoms in migraine within the paediatric population, or their ability to predict accurately the onset of an impending headache cannot be deduced from the retrospective studies performed to date, premonitory symptoms occur in children as young as 18 months old. Understanding the biological basis of these, and their heterogeneous phenotype may help future targeted therapeutic research, helping the development of drugs that act before the onset of pain, limiting the morbidity associated with the migraine attack.
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17.

Purpose of Review

Testing the efficacy of academic detailing in improving the practice of prescribing naloxone for patients on high-dose opioids.

Recent Findings

Academic detailing has been identified as an effective method for improving health care practices through focused community education.

Summary

We found that academic detailing is an effective method in improving health care providers’ knowledge about the importance of prescribing naloxone for patients on high-dose opioids. We also found that prescribers prescribed more naloxone after our education program. This study reflects the importance of education and academic detailing in resolving health problems. Academic detailing can provide effective preventive tools that can reduce the incidence of health problems we encounter.
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18.

Background

Resting state magnetic resonance imaging allows studying functionally interconnected brain networks. Here we were aimed to verify functional connectivity between brain networks at rest and its relationship with thalamic microstructure in migraine without aura (MO) patients between attacks.

Methods

Eighteen patients with untreated MO underwent 3 T MRI scans and were compared to a group of 19 healthy volunteers (HV). We used MRI to collect resting state data among two selected resting state networks, identified using group independent component (IC) analysis. Fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from a previous diffusion tensor imaging study on the same subjects and correlated with resting state ICs Z-scores.

Results

In comparison to HV, in MO we found significant reduced functional connectivity between the default mode network and the visuo-spatial system. Both HV and migraine patients selected ICs Z-scores correlated negatively with FA values of the thalamus bilaterally.

Conclusions

The present results are the first evidence supporting the hypothesis that an abnormal resting within networks connectivity associated with significant differences in baseline thalamic microstructure could contribute to interictal migraine pathophysiology.
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19.

Purpose of Review

This review is intended to examine how the diagnostic criteria for migraine have evolved over the past 45 years and to evaluate the strengths and weaknesses of the current diagnostic criteria promulgated by the International Classification of Headache Disorders (ICHD).

Recent Findings

The ICHD is a comprehensive and systematic classification system for headache disorders. As the pathophysiology of migraine is more fully elucidated and more sophisticated diagnostic technologies are developed (e.g., the identification of biomarkers), the current diagnostic criteria for migraine will likely be further refined. The ICHD has allowed for more precise research study design in the field of headache medicine.

Summary

The current diagnostic criteria for migraine outlined in the 3rd version of the ICHD are far more sensitive and specific than the clinical criteria proposed in 1962. In future iterations, dividing episodic and chronic migraine into subtypes based on frequency (i.e., low frequency vs high frequency; near-daily vs daily) potentially could assist in guiding clinical management. In addition, a better understanding of aura, vestibular migraine, migrainous infarction, and hemiplegic migraine likely will lead to more refined diagnostic criteria for those entities.
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20.

Purpose of Review

Nutraceuticals are a form of complementary and alternative medicine that is commonly used by children and adolescents with migraine. In this review, observational studies, randomized controlled trials, systematic reviews, and meta-analyses on the efficacy and safety of single compound nutraceuticals for the management of migraine in children and adolescents were identified through a literature search of MEDLINE, Embase, and EBM Reviews—Cochrane Central Register of Controlled Trials.

Recent Findings

Twenty-one studies were reviewed, of which 11 were observational studies, 7 were randomized controlled trials, and 3 were systematic reviews. Six different nutraceuticals were included in the review: vitamin D, riboflavin, coenzyme Q10, magnesium, butterbur, and polyunsaturated fatty acids. All but three of the studies assessed the role of nutraceuticals in migraine prevention, while three studies evaluated the role of intravenous magnesium for acute migraine management. Overall, the quality and size of the studies were limited.

Summary

Due to low quality evidence and limited studies, no definite conclusions can be drawn on the efficacy of nutraceuticals for the treatment of pediatric migraine. Future studies are warranted in order to establish evidence upon which to define the role of nutraceuticals in this patient population.
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