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1.

Purpose

Migraine is associated with vascular disorders, but the underlying mechanism is unknown. Nitric oxide (NO) sensitivity is believed to play a major role in migraine pathophysiology. We investigated flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation (NMD) of the brachial artery by means of a key molecular mediator, NO, in patients with migraine without aura in the interictal period whether the abnormality is found.

Methods

A total of 12 patients with migraine without aura and 12 matched healthy controls were enrolled in this study. FMD and NMD were measured in all patients and controls using brachial artery ultrasonography.

Results

There was no significant difference in brachial artery diameter between migraineurs and nonmigraineurs (3.39?±?0.68 vs 3.89?±?0.67 mm, respectively; p?=?0.083). A significant difference in FMD was not found between migraineurs and nonmigraineurs (6.94?±?5.72 vs 6.08?±?2.98%, respectively; p?=?0.651). However, NMD in migraineurs was significant higher than that in nonmigraineurs (21.56?±?7.36 vs 14.23?±?7.41%, respectively; p?=?0.024).

Conclusion

We think that patients with migraine without aura in the interictal period have selective sensitivity in dilator response to nitroglycerin and may have systemic NO sensitivity.
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2.

Background

Menstrual migraine (MM) and premenstrual syndrome (PMS) are two conditions linked to specific phases of the menstrual cycle. The exact pathophysiological mechanisms are not fully understood, but both conditions are hypothesized to be triggered by female sex hormones. Co-occurrence of MM and PMS is controversial. The objective of this population-based study was to compare self-assessed symptoms of PMS in female migraineurs with and without MM. A total of 237 women from the general population who self-reported migraine in at least50% of their menstruations in a screening questionnaire were invited to a clinical interview and diagnosed by a neurologist according to the International Classification of Headache Disorders II (ICHD II), including the appendix criteria for MM. All women were asked to complete a self-administered form containing 11 questions about PMS-symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. The number of PMS symptoms was compared among migraineurs with and without MM. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS).

Findings

A total of 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n?=?61) or because they did not fulfil the ICHD-criteria for migraine (n?=?6). Among the remaining 126 migraineurs, 78 had MM and 48 non-menstrually related migraine. PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs. 5.9, p?=?0.84). Women with MM reported more migraine days/month, longer lasting migraine attacks and higher HIT-6 scores than those without MM, but MIDAS scores were similar.

Conclusion

We did not find any difference in number of self-reported PMS-symptoms between migraineurs with and without MM.
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3.

Objectives

1) to assess the prevalence of hepatitis C virus (HCV) infection in a population of acute psychiatric in-patients; 2) to find out relationships between HCV comorbidity and clinical features of psychiatric patients.

Methods

Prospective observational study in a 6-year period.

Results

2396 cases (1492 patients) were admitted in the considered period. Forty-two patients (2.8%) were affected by HCV infection. HCV infection was more frequent in patients with less years of education, lower social class, lower last year best Global Assessment of Functioning score, more hostile or violent behavior in hospital, with a lifetime history of previous suicide attempt, and with substance-related disorders.

Conclusion

HCV infection in psychiatric patients constitutes a major threat to the health of psychiatric patients and is related with unfavorable social background, worse global functioning, hostile or violent behavior, substance-related disorders. It appears also to be a significant risk of suicidal behavior.
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4.

Background

Information on mental health sequel in adolescents following natural disasters from developing countries is scant.

Method

Around one year after a super-cyclone, proportion of adolescents exhibiting post-traumatic psychiatric symptoms, prevalence of post-traumatic stress disorder (PTSD), major depression and generalized anxiety disorder, comorbidity and impairment of performance in school were studied in Orissa, India. Mini International Neuropsychiatric Interview for children and adolescents was used for evaluation and diagnosis. The criteria for diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders – IV.

Results

Post-disaster psychiatric presentation in adolescents was a conglomeration of PTSD, depression and anxiety symptoms. The prevalences of PTSD, major depressive disorder and generalised anxiety disorder were 26.9%, 17.6% and 12.0% respectively. Proportion of adolescents with any diagnosis was 37.9%. Comorbidity was found in 39.0% of adolescents with a psychiatric diagnosis. Adolescents from middle socioeconomic status were more affected. There were gender differences in the presentation of the symptoms rather than on the prevalence of diagnoses. Prolonged periods of helplessness and lack of adequate post-disaster psychological support were perceived as probable influencing factors, as well as the severity of the disaster.

Conclusion

The findings of the study highlight the continuing need for identification and intervention for post-disaster psychiatric morbidities in adolescent victims in developing countries.
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5.

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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6.

Introduction

Nalmefene is the first drug to be approved for reducing alcohol consumption in alcohol use disorder (AUD) patients at high drinking risk. In real-world settings, there is a high prevalence of concurrent psychiatric disorders in AUD subjects, with associated increased morbidity and worse prognosis. This study evaluated the use of nalmefene in AUD patients with stabilized psychiatric comorbidity previously treated unsuccessfully for alcohol dependence, and assessed craving reduction and safety.

Methods

Sixty-five AUD outpatients treated with as-needed 18 mg nalmefene for 24 weeks were included. Primary outcome measures were: changes in heavy drinking days (HDDs) and total alcohol consumption (TAC, g/day). Secondary outcome measures were: changes in drinking risk level and craving (obsessive–compulsive drinking scale and visual analogue scale for craving).

Results

Forty-two AUD subjects (64.6%) had one or more stabilized psychiatric comorbidity. There was a significant reduction in HDDs, TAC and craving measures (p < 0.001), with no differences between subjects with and without psychiatric comorbidity. Nalmefene was safe and well tolerated in all patients.

Conclusion

As-needed nalmefene reduced drinking and craving in AUD subjects with and without psychiatric comorbidity. These findings suggest that nalmefene is a valid therapeutic option in real-world clinical settings, where comorbid conditions are common, and has the potential to engage AUD patients who may otherwise not have sought help.

Funding

Lundbeck Italia S.P.A.
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7.

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.

Summary

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.
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8.

Introduction

We sought to characterize changes in healthcare spending associated with the onset of 22 endometriosis-related comorbidities.

Methods

Women aged 18–49 years with endometriosis (N = 180,278) were extracted from 2006–2015 de-identified Clinformatics® DataMart claims data. For 22 comorbidities, comorbidity patients were identified on the basis of having a first comorbidity diagnosis after their initial endometriosis diagnosis. Controls were identified on the basis of having no comorbidity diagnosis and were matched 1:1 to comorbidity patients on demographics and baseline spending. Total medical and pharmacy spending was measured during 12 months before and after each patient’s index date (first comorbidity diagnosis for comorbidity patients, and equal number of days after earliest endometriosis claim for controls). Pre–post spending differences were compared using difference-in-differences linear regression. Total and comorbidity-related cumulative spending per patient for all endometriosis patients were calculated annually for the 5 years following endometriosis diagnosis.

Results

The number of endometriosis patients with each comorbidity varied between 121 for endometrial cancer and 16,177 for fatigue. Healthcare spending increased significantly with the onset of eight comorbidities: breast cancer, ovarian cancer, pregnancy complications, systemic lupus erythematosus/rheumatoid arthritis/Sjogren’s/multiple sclerosis, infertility, uterine fibroids, ovarian cyst, and headache [p < 0.001 except for headache (p = 0.045)]. Spending decreased significantly for fatigue, cystitis/UTI, and eczema [p < 0.001 except for fatigue (p = 0.048)] and was not statistically different for the other 11 comorbidities. Difference-in-differences estimates were significantly higher for comorbidity patients for all comorbidities except eczema (p ≤ 0.003). Mean 5-year total cumulative spending was $58,191 per endometriosis patient, of which between 11% and 23% was attributable to comorbidity-related medical claims.

Conclusion

For all but one of the 22 comorbidities associated with endometriosis, comorbidity onset was associated with a relative increase in total healthcare spending.

Funding

AbbVie Inc.
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9.

Background

Migraine is a neurological disorder resulting in large socioeconomic burden. This network meta-analysis (NMA) is designed to compare the relative efficacy and tolerability of non-steroidal anti-inflammatory agents (NSAIDs) and triptans.

Methods

We conducted systematic searches in database PubMed and Embase. Treatment effectiveness was compared by synthesizing direct and indirect evidences using NMA. The surface under curve ranking area (SUCRA) was created to rank those interventions.

Results

Eletriptan and rizatriptan are superior to sumatriptan, zolmitriptan, almotriptan, ibuprofen and aspirin with respect to pain-relief. When analyzing 2 h-nausea-absence, rizatriptan has a better efficacy than sumatriptan, while other treatments indicate no distinctive difference compared with placebo. Furthermore, sumatriptan demonstrates a higher incidence of all-adverse-event compared with diclofenac-potassium, ibuprofen and almotriptan.

Conclusion

This study suggests that eletriptan may be the most suitable therapy for migraine from a comprehensive point of view. In the meantime ibuprofen may also be a good choice for its excellent tolerability. Multi-component medication also attracts attention and may be a promising avenue for the next generation of migraine treatment.
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10.

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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11.

Purpose of Review

Migraine is a disabling and prevalent neurological disease, commonly affecting women during their reproductive years. It is crucial for providers to be able to adequately counsel women who are pregnant, planning pregnancy, or nursing, regarding preventive and abortive treatment options for episodic migraine. This review will discuss (1) the expected course of migraine during pregnancy and the post-partum period, (2) recommended preventive therapies for migraine during pregnancy and lactation, and (3) recommended abortive medications for migraine during pregnancy and lactation.

Recent Findings

Recent research has indicated safety for triptan use during pregnancy and ibuprofen use during the first trimester of pregnancy. Considerations for use of emerging migraine-preventive treatment, such as non-invasive neurostimulators, are discussed.

Summary

For clinical decision-making and patient counseling, it is important to understand both the limitations in determining teratogenic effects in humans and the principles affecting medication transmission from mother to breast milk.
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12.

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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13.

Purpose of Review

Migraine is a common and highly disabling condition that is particularly prevalent among women and especially women of reproductive age. The tremendous rise in adiposity in the Western world has led to an epidemic of obesity in women. The particular effects of obesity on women with migraine of various ages are the focus of this review.

Recent Findings

Conflicting findings from various studies with different approaches and populations have made challenging definitive conclusions about associations between migraine and obesity. While the association between obesity and migraine frequency has been consistently demonstrated and obesity is considered a risk factor for progression from episodic to chronic migraine, the association between obesity and migraine prevalence is still somewhat debated and appears to be dependent on gender and age, with the most consistent effects observed in women younger than 55 years of age.

Summary

Association between migraine and obesity is most commonly observed in women of reproductive age. The multimodal changes associated with age and hormonal change in women likely play a role in this relationship, as obesity does not appear to be related to migraine in women over 55 years of age. Future studies focusing on the migraine-obesity relationship in women should examine the effects of age, endogenous hormonal state, and exogenous hormones on migraine and obesity.
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14.

Purpose of Review

The purpose of this work was to review the current literature on the epidemiology and pathophysiology of pediatric obesity and migraine, underlying pathogenic mechanisms that may explain the association between the two disorders, and the effects of treatment.

Recent Findings

In children and adolescents, the bulk of the available data support an association between obesity and headache disorders in general, though a small number of studies contradict these findings. Relative to the adult population, however, few studies have focused specifically on migraine, and no wide-ranging meta-analyses have been conducted to date. It seems that the pathophysiology of obesity and migraine in adults holds true for the pediatric population as well. The association between obesity and migraine in the pediatric population is likely to be multifactorial and to involve both central and peripheral mechanisms. More attention is currently being addressed to the role of the hypothalamus and the bioactive neurotransmitters and neuropeptides that modulate energy homeostasis, namely serotonin, orexin, and the adiponectins, in migraine. A few innovative studies have demonstrated some benefit for migraine from weight reduction treatments such as exercise and lifestyle management.

Summary

Many open questions remain regarding the modifiable nature of the obesity–migraine relationship and its implications in clinical practice. Further studies of these issues are needed.
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15.

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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16.

Objective

To estimate 12-month prevalence and co-occurrence of symptoms of specific mental problems among US adolescents (12–17 years) by age, sex and racial/ethnic subgroups.

Method

Data from the 2000 National Household Survey of Drug Abuse (NHSDA) adolescent sample are used to estimate prevalence and co-occurrence rates using the DISC predictive scales. Multiple logistic regressions were used to derive significant correlates of each domain of DPS-derived symptom cluster indicators of psychiatric problems and of severe comorbidity, with control of demographics and environmental factors.

Setting

The National Household Survey on Drug Abuse (NHSDA), a national household probability sample, includes a nationally representative sample of 12–17 year-old adolescents (N = 19,430), through in-home surveys.

Results

Three out of five adolescents screened positive for at least one DPS symptom cluster with estimates for specific symptom cluster ranging over 9.7% (substance use disorder), 13.4% (affective), 36.3% (disruptive-behavior), and 40.1% (anxiety). Co-occurrence was high with almost one-third of any DPS symptom cluster reporting multiple positive screens of four or more clusters. Blacks and younger females were most likely to report mental health problems and co-occurrence.

Conclusion

Mental health problems among U.S. youth may be far more common than previously believed, although these symptoms have not yet reached the point of clinical impairment. The data speak to important patterns of age, gender and racial/ethnic differences in mental health problems deserving of further study.
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17.

Background

Owing to a rise of psychosomatic comorbidities, the treatment of psychological disorders, which may negatively impact prognosis and therapy, is increasingly becoming a focus of attention for pain outpatient clinics.

Aim

This study investigates and discusses the advantages of liaison psychiatric care in a university pain clinic.

Methods

In this retrospective study, we investigated all patients who presented to an anaesthesiologically led pain clinic between January and June 2014. The psychiatric history was taken by the liaison psychiatrist of the pain clinic.

Results

In the period investigated, 485 patients were treated as outpatients. A psychiatric diagnosis was present 351 patients (72.4%). The distribution of the diagnoses was comparable with that of a consultation service. Adaptation and affective disorders dominated. The patients were preferentially treated with new generation antidepressants.

Conclusion

The constant presence of a liaison psychiatrist allows for timely, specialised care of pain patients in terms of a multimodal therapeutic approach.
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18.

Purpose of Review

To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura.

Recent Findings

The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe.

Summary

The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.
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19.

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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20.

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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