Migraine disorders Research Papers - Academia.edu (original) (raw)

A recent fMRI study showed that dorsolateral prefrontal cortex (DLPFC) exerts an inhibitory control on pain pathways in humans. We investigated whether high-frequency rTMS over left DLPFC could ameliorate chronic migraine. Treatment... more

A recent fMRI study showed that dorsolateral prefrontal cortex (DLPFC) exerts an inhibitory control on pain pathways in humans. We investigated whether high-frequency rTMS over left DLPFC could ameliorate chronic migraine. Treatment consisted of 12 rTMS sessions, delivered in alternate days over left DLPFC. Sham rTMS was used as placebo. Eleven patients were randomly assigned to the rTMS (n=6) or to the placebo (n=5) treatment. Measures of attack frequency, headache index, number of abortive medications (outcome measures) were recorded in the month before, during and in the month after treatment. Subjects treated by rTMS showed a significant reduction of the outcome measures during and in the month after the treatment as compared to the month before treatment. No significant differences in the outcome measures were observed in the placebo group. High-frequency rTMS over left DLPFC was able to ameliorate chronic migraine. This is in agreement with the suggested role of DLPFC in pain control.

Recurrent limb pain (RLP) is a well-known entity in childhood. It is considered a precursor of migraine. The temporal relationship of RLP with headache in childhood is lacking in the literature. However, there are many cases with limb... more

Recurrent limb pain (RLP) is a well-known entity in childhood. It is considered a precursor of migraine. The temporal relationship of RLP with headache in childhood is lacking in the literature. However, there are many cases with limb pain in a close temporal relationship with migraine headache in adults. We report six female patients with RLP and migraine and delineate the temporal relationship between the two. Three patients had a history of RLP in childhood and developed migraine headache after many years. Conversely, two patients had a long history of migraine headache and later developed RLP. One patient developed RLP and migraine headache at the same age. Isolated limb pain was frequent in all six patients. It was mild to severe, for a few minutes to a few days, and predominantly located in the upper extremities. Only one patient reported allodynia. The patients showed response to preventive measures (all six patients) and abortive therapies (four patients), even in those attacks of RLP that were not associated with headache episodes. We also review the clinical profiles of the patients in whom RLP and migraine were related to each other, and speculate on the possible mechanisms for RLP in the patients with migraine. ᮀ Limb pain, headache, migraine

Migraine is a common neurological episodic disorder with a female-to-male prevalence 3-to 4-fold higher, suggesting a possible X-linked genetic component. Our aims were to assess the role of common variants of gammaaminobutyric acid A... more

Migraine is a common neurological episodic disorder with a female-to-male prevalence 3-to 4-fold higher, suggesting a possible X-linked genetic component. Our aims were to assess the role of common variants of gammaaminobutyric acid A receptor (GABA A R) genes, located in the X-chromosome, in migraine susceptibility and the possible interaction between them. An association study with 188 unrelated cases and 286 migraine-free controls age-and ethnic matched was performed. Twenty-three tagging SNPs were selected in three genes (GABRE, GABRA3 and GABRQ). Allelic, genotypic and haplotypic frequencies were compared between cases and controls. We also focused on gene-gene interactions. The AT genotype of rs3810651 of GABRQ gene was associated with an increased risk for migraine (OR: 4.07; 95% CI: 1.71-9.73, p=0.002), while the CT genotype of rs3902802 (OR: 0.41; 95% CI: 0.21-0.78, p=0.006) and GA genotype of rs2131190 of GABRA3 gene (OR: 0.53; 95% CI: 0.32-0.88, p=0.013) seem to be protective factors. All associations were found in the female group and maintained significance after Bonferroni correction. We also found three nominal associations in the allelic analyses although there were no significant results in the haplotypic analyses. Strikingly, we found strong interactions between six SNPs encoding for different subunits of GABA A R, all significant after permutation correction. To our knowledge, we show for the first time, the putative involvement of polymorphisms in GABA A R genes in migraine susceptibility and more importantly we unraveled a role for novel gene-gene interactions opening new perspectives for the development of more effective treatments.

Twenty patients with complex neuropsychologic symptoms associated with classic migraine were selected from a group of 200 patients with vascular headache. Twenty types of symptoms were found and grouped into six categories (language,... more

Twenty patients with complex neuropsychologic symptoms associated with classic migraine were selected from a group of 200 patients with vascular headache. Twenty types of symptoms were found and grouped into six categories (language, visual symptoms, cognitive-dysmnesic symptoms, olfactory-gustatory hallucinations, automatisms, and somatosensory symptoms). Some of the symptoms found have apparently not been reported previously. The importance of the analysis of this complex neuropsychologic set of symptoms and of the possible consequences of complicated, frequent vascular headache is emphasized. • Classic migraine, neuropsychologic symptoms

Objectives.-The aim of our study is to determine the prevalence of migraine in Provincial Center of Edirne. Methods.-A systematic random sample of 386 inhabitants over 14 years old were interviewed face to face. Diagnosis of migraine was... more

Objectives.-The aim of our study is to determine the prevalence of migraine in Provincial Center of Edirne. Methods.-A systematic random sample of 386 inhabitants over 14 years old were interviewed face to face. Diagnosis of migraine was based on the International Headache Society (IHS) classification. Results.-Migraine was identified in 77 subjects (60 female, 17 male). The lifetime prevalence of migraine was found to be 19.9% (95% CI: 18.3-21.5) (9.34% (95% CI: 8.6-10) in males, 29.3% (95% CI: 27-31.6) in females). Conclusions.-These results show that while migraine prevalence in Turkish females is higher than that reported in previous studies from Europe and United States, lifetime prevalence is similar in all populations.

Objective.-To describe the relationship between mood/anxiety disorders and migraine headaches emphasizing the frequency of episodes based in a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health. Background.-It... more

Objective.-To describe the relationship between mood/anxiety disorders and migraine headaches emphasizing the frequency of episodes based in a cross-sectional analysis in the Brazilian Longitudinal Study of Adult Health. Background.-It has been suggested that frequency of migraine headaches can be directly associated with the presence of psychiatric disorders. Methods.-Migraine headaches (International Headache Society criteria) was classified as <1×/month, 1×/month-1×/week, 2-6×/week, and daily. Psychiatric disorders using the Clinical Interview Schedule-Revised were classified in 6 categories: common mental (CMD), major depressive (MDD), generalized anxiety (GAD), panic, obsessive-compulsive (OCD), and mixed anxiety and depressive (MADD) disorders. We performed multivariate logistic models adjusted for age, race, education, marital status, income, and use of selective serotonin reuptake inhibitors. Results.-In our sample, 1261 presented definite migraine and 10,531 without migraine headaches (reference). Our main result was an increase in the strength of association between migraine and MDD as frequency of migraine increased for all sample: odds ratio of 2.14 (95% confidence interval [CI] 1.33-3.43) for <1 episode of migraine/month to 6.94 (95% CI 4.20-11.49) for daily headaches for all sample. Significant associations with migraine were also found for GAD, OCD, MADD, and CMD for total sample: MDD, GAD, OCD, MADD, and CMD for women, and MADD and CMD for men. Among men with daily migraine complaint, we found a significant association between migraine and OCD after correction for multiple comparisons (odds ratio 29.86 [95% CI 4.66-191.43]). Analyzing probable and definite migraine cases together, we replicated the findings in a lower magnitude. Conclusions.-The increase in migraine frequency was associated with progressively higher frequencies of having mood/ anxiety disorders in all samples suggesting for some psychiatric disorders a likely dose-response effect especially for women.

Although anxiety disorders and headaches are comorbid conditions, there have been no studies evaluating the prevalence of primary headaches in patients with generalized anxiety disorder (GAD). The aim of this study was to analyze the... more

Although anxiety disorders and headaches are comorbid conditions, there have been no studies evaluating the prevalence of primary headaches in patients with generalized anxiety disorder (GAD). The aim of this study was to analyze the lifetime prevalence of primary headaches in individuals with and without GAD. A total of 60 individuals were evaluated: 30 GAD patients and 30 controls without mental disorders. Psychiatric assessments and primary headache diagnoses were made using structured interviews. Among the GAD patients, the most common diagnosis was migraine, which was significantly more prevalent among the GAD patients than among the controls, as were episodic migraine, chronic daily headache and aura. Tension-type headache was equally common in both groups. Primary headaches in general were significantly more common and more severe in GAD patients than in controls. In anxiety disorder patients, particularly those with GAD, accurate diagnosis of primary headache can improve patient management and clinical outcomes.

Four hundred eighty-five patients between the ages of 15 and 89 made 631 visits to a medical center emergency department with a chief complaint of headache or head pain during a 12-month period from May 1977 to April 1978, accounting for... more

Four hundred eighty-five patients between the ages of 15 and 89 made 631 visits to a medical center emergency department with a chief complaint of headache or head pain during a 12-month period from May 1977 to April 1978, accounting for 1.6% of all patient visits. One hundred ninety-three (40%) had subsequent follow-up data available for review. Muscle contraction-tension headache and migraine headache were the most common diagnoses, accounting for 54.5% of all patients. The female/male distribution was 3:2 for the entire group. Five percent of the overall group had serious neurological conditions. Analysis of the emergency department evaluations, results of follow-up, and reviews of other recent series are reported. Based on current literature, recommendations for the detailed laboratory evaluation of the suspicious headache are described. Leicht M J: Non-traumatic headache in the emergency department. Ann Emerg Med 9:404-409, August 1980. headache, non-traumatic, evaluation in emergency department; neurologic condition., headache, evaluation in emergency department I NTRODUCTION Emergency departments throughout the country are experiencing an increase in patient visits. 1,2 Many factors contribute to this increase, not the least of which is 24-hour availability of medical care. 3 At Geisinger Medical Center we have noted an increase in the number of patients using the emergency department as their community physician. 4 The patient with headache often falls into this category. The number of people Who have experienced headache approaches 90% of the population.~, ~ In a survey by the National Center for Health Statistics, 13.7% of men and 27.8% of women said their headaches occurred "every few days" or !'quite a bit. ''~ As a result of the overall number and the increasing frequency of this problem in the emergency, department, the recent advances in laboratory evaluation of suspicious headache, the dilemma regarding optimal outpatient evaluation, indicators of true emergencies, and proper avenues of referral, this study was undertaken. The objective was to identify the patient population that presents with headache, establish the frequency of expected diagnoses, search for helpful epidemiological and historical clues to diagnosis in a large patient population frequently devoid of physical findings, identify the subgroup of patients with serious neurological conditions and, finally, determine the optimal laboratory evaluation available to the emergency physician, MATERIALS AND METHODS In a 12-month period from May 1977 to April 1978, the emergency department at Geisinger Medical Center had 40,000 patient visits. During this time, 485 patients 15 years old and older made 631 visits to our department (1.6% of total visits) with the chief complaint of"headache" or "head pain" (Figure 1). None

Migraine is a highly prevalent condition and an important cause of disability. Although the pathogenesis of this condition is complex and multifaceted, several environmental factors have been associated with development and aggravation of... more

Migraine is a highly prevalent condition and an important cause of disability. Although the pathogenesis of this condition is complex and multifaceted, several environmental factors have been associated with development and aggravation of headache attacks. Among the various foods that have been implicated in migraine, chocolate has been regarded as detrimental on the basis of old and mostly anecdotal evidence. Therefore, this article is aimed to provide an overview on the current scientific evidence about the relationship between chocolate and migraine. Taken together, the information gathered from epidemiological and provocative studies attests that the potential causal association between chocolate and migraine remains largely enigmatic. The analysis of epidemiological surveys reveals a highly heterogeneous picture, with frequency of migraine episodes attributable to chocolate ranging from 0 to 22.5%. Even in those studies reporting a more convincing association, the risk of migra...

About 4 per cent of schoolchildren suffer from migraine. In some cases the attacks can be frequent and severe. Often symptomatic and prophylactic treatments are either ineffective or cause pronounced side effects. Therc have been reports... more

About 4 per cent of schoolchildren suffer from migraine. In some cases the attacks can be frequent and severe. Often symptomatic and prophylactic treatments are either ineffective or cause pronounced side effects. Therc have been reports on studies in which a prophylactic effect on migraine by propranolol has been noted. This beta-receptor blocking agent has been tested in a double-blind single crossover study in 32 children aged 7-16 with migraine. Propranolol had an excellent prophylactic effect on migraine attacks. Since propranolol does not cause serious sidc effects provided certain patients are excluded, it seems justifiable to recommend this preparation where prophylactic therapy is indicated in cases of severe and frequent migraine.

OBJECTIVE To compare the levels of trace elements and heavy metal in patients with acute migraine and healthy controls. METHODS The prospective study was conducted at Yuzuncu Yil University, Turkey, from May to July 2013, and comprised... more

OBJECTIVE To compare the levels of trace elements and heavy metal in patients with acute migraine and healthy controls. METHODS The prospective study was conducted at Yuzuncu Yil University, Turkey, from May to July 2013, and comprised migraine patients and an equal number of healthy controls. International Headache Society classification was used for diagnosing migraine. Serum copper, zinc, lead, iron, cadmium, cobalt, manganese, and magnesium levels were measured in both groups. Metal concentrations were assessed by atomic absorption spectrophotometry. SPSS 13 was used for statistical analysis. RESULTS There were 25 migraine patients with an average age of 36.4±8.9 years and 25 healthy controls with a mean age of 42.4±9.5 years. Cadmium, iron, manganese and lead levels were significantly elevated in the patients compared to the controls (p<0.05 each), while copper, magnesium and zinc were decreased and cobalt demonstrated no change. CONCLUSIONS Trace elements and heavy metals m...

Calcitonin gene-related peptide (CGRP) is a well-studied neuropeptide of relevance for migraine pathophysiology. Jugular levels of CGRP are increased during migraine attacks, and intravenous CGRP administration induces migraine-like... more

Calcitonin gene-related peptide (CGRP) is a well-studied neuropeptide of relevance for migraine pathophysiology. Jugular levels of CGRP are increased during migraine attacks, and intravenous CGRP administration induces migraine-like headache in most individuals with migraine. Several CGRP receptor antagonists (CGRP-RAs) were shown to be effective for the acute treatment of migraine, validating the target for the treatment of migraine. However, for a number of reasons, including issues of liver toxicity with chronic use, the development of CGRP-RAs has yet to produce a viable clinical therapeutic. Development of monoclonal antibodies (mAbs) targeting the CGRP pathway is an alternative approach that should avoid many of the issues seen with CGRP-RAs. The exquisite target specificity, prolonged half-lives, and reduced potential for hepatotoxicity and drug-drug interactions make mAbs suitable for the preventive treatment of migraine headaches. This manuscript provides an overview of the role of CGRP in the pathophysiology of migraine, followed by a review of the clinical development of CGRP-RAs. Some basic concepts on antibodies are then discussed along with the publicly disclosed information on the development of mAbs targeting the CGRP pathway. Key Points Calcitonin gene-related peptide (CGRP) is relevant to migraine pathophysiology. CGRP receptor antagonists have demonstrated proof of efficacy for the acute treatment of migraine, but were discontinued because of safety or formulation problems. Monoclonal antibodies exhibit exquisite target specificity, prolonged half-lives, and reduced potential for hepatotoxicity and drug-drug interactions, and are suitable for the preventive treatment of migraine headaches. Four monoclonal antibodies targeting CGRP or its receptor are being developed for the preventive treatment of episodic migraine, with two of them also focusing on chronic migraine.

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associated with musculoskeletal pain, fatigue and headache. Migraine... more

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associated with musculoskeletal pain, fatigue and headache. Migraine with or without aura is considered the most common form of headache in JHS/EDS-HT. In this population of chronically ill patients, we investigated whether migraine characteristics were different from those of a control population of migraine patients. The study was carried out on 33 selected JHS/EDS-HT patients, diagnosed according to current criteria. Sixty-six migraine subjects matching age and gender were consecutively selected as controls (MO group) among patients attending our Headache Clinic. JHS/EDS-HT and MO were screened for a series of headache characteristics, such as frequency, intensity, age of onset, level of disability, use of rescue and prophylactic medications. Differences between the two groups were tested by using independent grou...

A procedure was developed for the determination of the analgesic components of Spasmomigraine Ò tablets, which are ergotamine (I), propyphenazone (II), caffeine (III), camylofin (IV), and mecloxamine (V). They were subjected to... more

A procedure was developed for the determination of the analgesic components of Spasmomigraine Ò tablets, which are ergotamine (I), propyphenazone (II), caffeine (III), camylofin (IV), and mecloxamine (V). They were subjected to high-performance liquid chromatography on a column (300´3.9 mm, 10 mm particle size) packed with m-Bondapak C18. Separations were achieved with the mobile phase methanol-water-triethylamine (60 + 40 + 0.1, v/v/v) flowing at a rate of 1.5 mL/min, and quantitative determination was performed at 254 nm at ambient temperature for I-III; acetonitrile-25 mM KH 2 PO 4-acetic acid (45 + 55 + 0.2, v/v/v), flowing at a rate of 1.5 mL/min and detection at 234 nm at ambient temperature, was used for IV and V. Methyl paraben was used as an internal standard. The detection limits were 0.35 (I), 5.0 (II), 1.5 (III), 3.0 (IV), and 2.0 mg/mL (V). The method was accurate (mean recovery 98 ± 2%, n = 4) and precise (coefficient of variation <5%, n = 5). The proposed method is rapid and sensitive and, therefore, suitable for the routine control of these ingredients in multicomponent dosage forms.

long, medium and short wavelength sensitive cones; cpd-cycles per degree; Y-luminance; cd m-2-candelas per metre squared; GII-general illusion index; CLCG-Cambridge low contrast gratings; MB (r,b) coordinates -Macleod-Boynton (1979)... more

long, medium and short wavelength sensitive cones; cpd-cycles per degree; Y-luminance; cd m-2-candelas per metre squared; GII-general illusion index; CLCG-Cambridge low contrast gratings; MB (r,b) coordinates -Macleod-Boynton (1979) chromaticity coordinates ; VTI-visual trigger index.

The aim of this large, cross-sectional, population-based study was to examine the association between sick leave and headache. Between 1995 and 1997, all 92 566 adults in Nord-Tr⊘ndelag County in Norway were invited to participate in a... more

The aim of this large, cross-sectional, population-based study was to examine the association between sick leave and headache. Between 1995 and 1997, all 92 566 adults in Nord-Tr⊘ndelag County in Norway were invited to participate in a health survey. Out of 73 327 invited individuals <67 years old, a total of 38 192 (52±) responded to questions about headache, work situation and sick leave during the past year. Associations between sick leave, headache and migraine included were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95± confidence intervals (CIs). There was an increasing prevalence of sick leave with increasing frequency of migraine and non-migrainous headache. The prevalence of sick leave >8 weeks during the past year was more than three times higher among individuals with headache >14 days per month (20±) compared with those without headache (6±). The results may indicate that better treatment of individuals with chronic headache ...

Headache is a vast field with many different varieties of headaches and classifications. However, all headaches have a common anatomy and physiology. All headaches are mediated by the trigeminocervical nucleus, and are initiated by... more

Headache is a vast field with many different varieties of headaches and classifications. However, all headaches have a common anatomy and physiology. All headaches are mediated by the trigeminocervical nucleus, and are initiated by noxious stimulation of the endings of the nerves that synapse on this nucleus, by irritation of the nerves themselves, or by disinhibition of the nucleus. A mastery of the relevant anatomy and physiology of the trigeminocervical nociceptive system serves to predict and summarise the many varieties of headache systematically and with reference to their mechanisms.

Because of the inextricable link between the eyes and headaches, ophthalmologists are often the fi rst physicians to evaluate patients with headaches, eye pain, and headache-associated visual disturbances. Although ophthalmic causes are... more

Because of the inextricable link between the eyes and headaches, ophthalmologists are often the fi rst physicians to evaluate patients with headaches, eye pain, and headache-associated visual disturbances. Although ophthalmic causes are sometimes diagnosed, eye pain and visual disturbances are often neurologic in origin. Many primary headache disorders have ophthalmic features, and secondary causes of headache frequently involve the visual system. Both afferent and efferent symptoms and signs are associated with headache disorders. Moreover, the frontal or retro-orbital pain of some primary ophthalmic conditions may be mistaken for a headache disorder, particularly if the ophthalmologic examination is normal. This article reviews common ocular conditions that are associated with head pain, and some secondary causes of headache with neuroophthalmic manifestations.

Background: Migraine is a distressing disorder that is often triggered by stress and poor sleep. Only one randomized controlled trial (RCT) has assessed the effects of massage therapy on migraine experiences, which yielded some promising... more

Background: Migraine is a distressing disorder that is often triggered by stress and poor sleep. Only one randomized controlled trial (RCT) has assessed the effects of massage therapy on migraine experiences, which yielded some promising findings. Purpose: An RCT was designed to replicate and extend the earlier findings using a larger sample, additional stress-related indicators, and assessments past the final session to identify longer-term effects of massage therapy on stress and migraine experiences. Methods: Migraine sufferers (N = 47) who were randomly assigned to massage or control conditions completed daily assessments of migraine experiences and sleep patterns for 13 weeks. Massage participants attended weekly massage sessions during Weeks 5 to 10. State anxiety, heart rates, and salivary cortisol were assessed before and after the sessions. Perceived stress and coping efficacy were assessed at Weeks 4, 10, and 13. Results: Compared to control participants, massage participants exhibited greater improvements in migraine frequency and sleep quality during the intervention weeks and the 3 follow-up weeks. Trends for beneficial effects of massage therapy on perceived stress and coping efficacy were observed. During sessions, massage induced decreases in state anxiety, heart rate, and cortisol. Conclusions: The findings provide preliminary support for the utility of massage therapy as a nonpharmacologic treatment for individuals suffering from migraines.

Background : Friedrich Nietzsche (1844-1900), one of the most profound and influential modern philosophers, suffered since his very childhood from severe migraine. At 44 he had a mental breakdown ending in a dementia with total physical... more

Background : Friedrich Nietzsche (1844-1900), one of the most profound and influential modern philosophers, suffered since his very childhood from severe migraine. At 44 he had a mental breakdown ending in a dementia with total physical dependence due to stroke. From the very beginning, Nietzsche's dementia was attributed to a neurosyphilitic infection. Recently, this tentative diagnosis has become controversial. Objective : To use historical accounts and original materials including correspondence, biographical data and medical papers to document the clinical characteristics of Nietzsche's illness and, by using this pathography, to discuss formerly proposed diagnoses and to provide and support a new diagnostic hypothesis. Materials : Original letters from Friedrich Nietzsche, descriptions by relatives and friends, and medical descriptions. Original German sources were investigated. Biographical papers published in medical journals were also consulted. Results : Nietzsche suffered from migraine without aura which started in his childhood. In the second half of his life he suffered from a psychiatric illness with depression. During his last years, a progressive cognitive decline evolved and ended in a profound dementia with stroke. He died from pneumonia in 1900. The family history includes a possible vascular-related mental illness in his father, who died from stroke at 36. Conclusions : Friedrich Nietzsche's disease consisted of migraine, psychiatric disturbances, cognitive decline with dementia, and stroke. Despite the prevalent opinion that neurosyphilis caused Nietzsche's illness, there is lack of evidence to support this diagnosis. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) accounts for all the signs and symptoms of Nietzsche's illness. This study adds new elements to the debate and controversy about Nietzsche's illness. We discuss former diagnoses, comment on the history of a diagnostic mistake, and integrate for the first time Nietzsche's medical problems.

The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically... more

The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve...

Thirty-two patients aged 2-22 y with cyclic vomiting syndrome (CVS), and 64 age-and gender-matched controls were assessed to determine the nature, severity, precipitants and associated features of attacks and the incidence of potential... more

Thirty-two patients aged 2-22 y with cyclic vomiting syndrome (CVS), and 64 age-and gender-matched controls were assessed to determine the nature, severity, precipitants and associated features of attacks and the incidence of potential aetiological factors. The mean age of onset was 3.5 y. Patients experienced a mean of nine attacks per year, of average duration 2.4 d, and two-thirds missed more than 10 d of school per year. Patients were more likely to have migraine and coordination difficulties, a past history of forceps delivery and gastroesophageal reflux than controls. Compared with controls, subjects had a higher incidence of psychological symptoms (38% compared with 19%) and migraine (37% compared with 9%). CVS is a chronic, disabling condition and is a migraine variant, with attacks usually precipitated by stress and intercurrent infections. ٖ Cyclic vomiting syndrome, migraine

Spreading depression is a reversible response of brain tissue to a local insult. It has been postulated to be the physiological substrate for the aura phase of classic migraine. The properties and mechanisms of spreading depression were... more

Spreading depression is a reversible response of brain tissue to a local insult. It has been postulated to be the physiological substrate for the aura phase of classic migraine. The properties and mechanisms of spreading depression were studied in the parietal neocortex of the alfentanil-anesthesized rat, by using a cup electrode that provided close control of the electrical stimulus while allowing specific ion (K+) and potential recordings to be made directly beneath the cathode, the region of origin of the stimulus-induced spreading depression. Cathodal stimulation caused the extracellular K+ concentration to rise, and spreading depressions were observed when this concentration exceeded 8-12 mM in the upper 100-200 microns of cortex. In some experiments extracellular [K+] continued to increase for 5-10 sec after termination of the stimulus, without detectable after-discharge in the potential record, before subsiding. While spreading depression could easily be induced by pressure o...

Background: Tension and migraine headaches are the most prevalent types of headaches. Some emotional and psychological factors are associated with these headaches. Objectives: To elucidate the nature of individual differences in emotion... more

Background: Tension and migraine headaches are the most prevalent types of headaches. Some emotional and psychological factors are associated with these headaches.
Objectives: To elucidate the nature of individual differences in emotion regulation and repetitive negative thinking among patients with tension headaches and migraine and compare it with normal subjects.
Materials & Methods: In this cross-sectional, comparative study, the participants consisted of patients with tension headaches and migraine referring to the two neurology clinics in Isfahan City, Iran from 2019 to 2020. A diverse sample of patients (n =240) completed the difficulties in emotional regulation scale and perseverative thinking questionnaire. The Chi-square tests, Fisher’s exact test, GLM (generalized linear model), Tukey post hoc test, and LSD (least significant difference) test were used to analyze the obtained data in SPSS V. 21.
Results: The results indicated that patients with a high level of repetitive negative thinking reported increased difficulties in emotional regulation and impulse control, limited access to emotion regulation strategies, and lack of emotional clarity (P<0.05). Moreover, the tension headaches group showed a higher level of difficulties in emotional regulation and repetitive negative thinking than the migraine and control groups (P<0.001).
Conclusion: Weak emotional regulation and repetitive negative thinking are associated with migraine and, especially tension headaches. Therefore, therapeutic plans based on emotion regulation and thinking problems should be considered as a complementary and necessary treatment for these types of headaches.

There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine... more

There is an unmet need of pharmacological and non-pharmacological treatment options for migraine patients. Exercise can be used in the treatment of several pain conditions, including. However, what exact role exercise plays in migraine prevention is unclear. Here, we review the associations between physical exercise and migraine from an epidemiological, therapeutical and pathophysiological perspective. The review was based on a primary literature search on the PubMed using the search terms "migraine and exercise". Low levels of physical exercise and high frequency of migraine has been reported in several large population-based studies. In experimental studies exercise has been reported as a trigger factor for migraine as well as migraine prophylaxis. Possible mechanisms for how exercise may trigger migraine attacks, include acute release of neuropeptides such as calcitonin gene-related peptide or alternation of hypocretin or lactate metabolism. Mechanisms for migraine prev...

Transcutaneous electric nerve stimulation (TENS) is a non-pharmacological method which is widely used by medical and paramedical professionals for the management of acute and chronic pain in a variety of conditions. Similarly, it can be... more

Transcutaneous electric nerve stimulation (TENS) is a non-pharmacological method which is widely used by medical and paramedical professionals for the management of acute and chronic pain in a variety of conditions. Similarly, it can be utilized for the management of pain during various dental procedures as well as pain due to various conditions affecting maxillofacial region. This review aims to provide an insight into clinical research evidence available for the analgesic and non analgesic uses of TENS in pediatric as well as adult patients related to the field of dentistry. Also, an attempt is made to briefly discuss history of therapeutic electricity, mechanism of action of TENS, components of TENs equipment, types, techniques of administration, advantages and contradictions of TENS. With this we hope to raise awareness among dental fraternity regarding its dental applications thereby increasing its use in dentistry.

The diagnostic value of greater occipital and supra-orbital nerve blockades in patients with cervicogenic headache, migraine without aura, and tension-type headache was investigated. The pain reduction after greater occipital nerve... more

The diagnostic value of greater occipital and supra-orbital nerve blockades in patients with cervicogenic headache, migraine without aura, and tension-type headache was investigated. The pain reduction after greater occipital nerve blockade was significantly more marked in the cervicogenic ...

Background: The relationships between sleep and headaches are complex and manifold. About the variety of phenomena that can disrupt the sleep macrostructure and can impact its restorative function, the periodic limb movements disorder... more

Background: The relationships between sleep and headaches are complex and manifold. About the variety of phenomena that can disrupt the sleep macrostructure and can impact its restorative function, the periodic limb movements disorder (PLMd) can be considered as the most powerful. No studies are known about the role of PLMd in the pathophysiology of migraine in children. Aim of study is to assess the prevalence of PLMd and migraine and their relationship with disability and pain intensity in a pediatric sample, referred for migraine without aura by pediatricians. Methods: After a preliminary sleep habits screening with the Sleep Disturbances Scale for Children, 34 migraine subjects affected by migraine without aura (20 M, 14 F) (mean age 9.08; SD ± 2.28) and 51 volunteers healthy children (28 M, 23 F) (mean age 9.37; SD ± 1.81) accepted to underwent overnight PSG recordings in the Sleep Laboratory of the Clinic of Child and Adolescent Neuropsychiatry, in order to define the macrostructural sleep characteristics and the prevalence of PLMd. Subsequently, the migraineurs sample was studied in order to define the relationship between disability, pain intensity, therapeutical responsiveness and the presence of PLMd. Results: In the migraineurs children group, the individuals with PLM pathological index (PLMI ≥ 5) represent the 26.47% of sample and present higher frequency (p < 0.001), intensity (p < 0.001), duration (p = 0.006) and life impairment as scored in the PedMIDAS (p < 0.001) of headache and lower efficacy of prophylactic (p = 0.001) and acute (p = 0.006) pharmacological treatment than MoA children without PLM pathological index. Conclusions: This preliminary study indicates the potential value of the determination of the PLMd signs, and the importance of the PSG evaluation in children affected by migraine, particularly when the clinical and pharmacological management tend to fail in the attacks control.

This review presents the potential impact of high altitude exposure on preexisting neurological conditions in patients usually living at low altitude. The neurological conditions include permanent and transient ischemia of the brain,... more

This review presents the potential impact of high altitude exposure on preexisting neurological conditions in patients usually living at low altitude. The neurological conditions include permanent and transient ischemia of the brain, occlusive cerebral artery disease, cerebral venous thrombosis, intracranial hemorrhage and vascular malformations, multiple sclerosis, intracranial space-occupying lesions, dementia, extrapyramidal disorders, migraine and other headaches, and epileptic seizures. New developments in diagnostic work-up and treatment of preexisting neurological conditions are also mentioned where applicable. For each neurological disorder, the authors developed absolute and relative contraindications for a trip to high altitude. These recommendations are not based on the results of controlled randomized trials, but mainly on case reports, pathophysiological considerations, and extrapolations from the low altitude situation.

Fatigue can be defined as extreme and persistent tiredness, weakness or exhaustion that could be mental, physical or both. The main objective of this study is to validate three instruments to measure fatigue (Fatigue Symptom... more

Fatigue can be defined as extreme and persistent tiredness, weakness or exhaustion that could be mental, physical or both. The main objective of this study is to validate three instruments to measure fatigue (Fatigue Symptom Inventory-FSI, Fatigue Assessment Instrument-FAI, Fatigue Severity Scale-FSS) in patients with epilepsy (PWE). We used concurrent validity as a method of validation. Reliability of the fatigue scales was assessed in PWE. We applied the three selected questionnaires plus the Beck Depression Inventory (BDI) in PWE, healthy volunteers (HV) and patients with other neurological conditions. We studied 67 PWE, 34 HV and 56 patients with different neurological conditions. The mean fatigue scores in each group were as follows: (a) for the FSS, the score in HV was 2.6

Objective.-To assess the scaling properties, reliability, and validity of the revised Migraine-Specific Quality of Life Questionnaire (MSQ) (Version 2.1) (© 1992, 1996, 1998 Glaxo Wellcome Inc.). Background.-The MSQ is a disease-specific,... more

Objective.-To assess the scaling properties, reliability, and validity of the revised Migraine-Specific Quality of Life Questionnaire (MSQ) (Version 2.1) (© 1992, 1996, 1998 Glaxo Wellcome Inc.). Background.-The MSQ is a disease-specific, quality-of-life instrument with three hypothesized scales that has been developed, tested, and revised. Methods.-The study used a multicenter, nondrug, prospective, parallel group, quasi-experimental design. Patients with migraine were recruited at outpatient headache specialty practices and were administered the MSQ, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and migraine symptom questionnaires at baseline, 4 weeks, and 12 weeks. Internal consistency (Cronbach ␣) and 4-week test-retest reproducibility (intraclass correlation coefficients) were estimated to assess reliability. Construct validity was assessed using an adaptation of the Campbell and Fiske multitrait-multimethod approach and by correlating MSQ scores with symptom measures. Results.-A total of 267 subjects enrolled in the trial. The criteria for summated rating scales were all met. The internal consistency coefficients ranged from 0.86 to 0.96, and the intraclass correlation coefficients ranged from 0.57 to 0.63 across the three dimensions. As anticipated, the MSQ dimensions had low-to-modest correlations with the two component scores of the SF-36 and were modestly to moderately correlated with migraine symptoms. Conclusions.-The MSQ is a reliable instrument in the assessment of quality of life for patients with migraine with items that can be summed without weights. The MSQ has demonstrated evidence of construct validity.

Background. There have been few studies on the relation between vitamin D and migraine. We investigated the prevalence of vitamin D deficiency in migraine patients and compared it with a control group. We also evaluated the relationship... more

Background. There have been few studies on the relation between vitamin D and migraine. We investigated the prevalence of vitamin D deficiency in migraine patients and compared it with a control group. We also evaluated the relationship of vitamin D deficiency with severity of migraine.Methods. 105 newly diagnosed migraine patients and 110 controls, matched for age, sex, socioeconomic status, education, and sun exposure, were enrolled during the spring of 2011. 25-Hydroxy vitamin D [25(OH)D] plasma levels were measured by chemiluminescence immunoassay.Results. The mean ± SE concentration of 25(OH)D was13.55±0.91 ng/mL in cases and13.19±1.19 ng/mL in controls. There was no significant difference in 25(OH)D concentration between cases and controls. We found no relationship between severity of headache and 25(OH)D status.Conclusions. We did not find any association between migraine and vitamin D status; also, severity of headaches was not related to 25(OH)D level. Further studies with ...

A case of atypical or complicated migraine is presented with signs and symptoms of meningeal irritation, projectile emesis NS obtundation, and unresponsiveness. The patient is a 19-year-old diabetic on insulin who had a mild episode of... more

A case of atypical or complicated migraine is presented with signs and symptoms of meningeal irritation, projectile emesis NS obtundation, and unresponsiveness. The patient is a 19-year-old diabetic on insulin who had a mild episode of upper respiratory tract symptoms with severe headache and was found unresponsive and brought to the emergency department. After a work-up for meningitis was negative (as well as computerized tomography and magnetic resonance imaging) he recovered totally in 3 days with no residual signs or symptoms and was discharged from the hospital.

Homeopathy is often advocated as a prophylaxis of migraine and headaches. The aim of this systematic review was to evaluate the clinical trials, testing the efficacy of homeopathy for these indications. Independent computerized literature... more

Homeopathy is often advocated as a prophylaxis of migraine and headaches. The aim of this systematic review was to evaluate the clinical trials, testing the efficacy of homeopathy for these indications. Independent computerized literature searches were carried out in 4 databases. Only randomized, placebo-controlled trials were included. Four such studies were found. Their methodological quality was variable but, on average, satisfactory. One study suggested that homeopathic remedies were effective. The other, methodologically stronger trials did not support this notion. It is concluded that the trial data available to date do not suggest that homeopathy is effective in the prophylaxis of migraine or headache beyond a placebo effect.

Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis as well as ef¯ux of excitatory amino acids from nerve cells and increased energy metabolism. There is strong clinical and experimental... more

Cortical spreading depression (CSD) is associated with a dramatic failure of brain ion homeostasis as well as ef¯ux of excitatory amino acids from nerve cells and increased energy metabolism. There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine. This paper will, based on the experience related to the detection of CSD in humans, discuss pitfalls and possible strategies for detection of CSD in man. Development of reliable methods for detection of CSD in humans will determine the extent to which the large body of experimental ®ndings from animal studies of CSD can be applied to the investigation and treatment of human brain disease. The paper is based on the experience that has been gained from two decades of studies of CSD in relation to clinical neurological diseases. u Cortical spreading, depression, cerebral blood¯ow

People who have migraine experience intermittent attacks of unilateral, pulsating, and moderate to severe headache with associated nausea or photophobia and phonophobia (or all these symptoms). These attacks typically start before the age... more

People who have migraine experience intermittent attacks of unilateral, pulsating, and moderate to severe headache with associated nausea or photophobia and phonophobia (or all these symptoms). These attacks typically start before the age of 40, often in childhood or teenage years, and occur most commonly from the second to the fourth decade of life. 1 Attacks may be infrequent or frequent. Chronic migraine is diagnosed when attacks regularly occur on more than 15 days a month. Box 1 shows the International Headache Society's classification criteria for migraine without aura. Recent population studies have shown the worldwide prevalence of migraine to be greater than 10%. The prevalence of migraine in the United States has been estimated at 18% for women, 6% for men, and 12% overall. 2 3 Migraine clearly affects women more than men, and its aetiology also seems to have a hereditary component. The World Health Organization ranks migraine 19th on the list of diseases worldwide that cause disability. w1 In spite of recent advances in treatment options for migraine, both acute and preventive, these treatments continue to be underused, 3 4 which leaves patients with unnecessary suffering and increases the burden on the healthcare system. We review the different types of preventive treatment and discuss how they should be used to treat migraine effectively.

Background: Measuring quality of life (QOL) is an important means of assessing the impact of headache. The currently used QOL questionnaires are usually geared toward migraine and focus on a limited number of factors, thus they are not... more

Background: Measuring quality of life (QOL) is an important means of assessing the impact of headache. The currently used QOL questionnaires are usually geared toward migraine and focus on a limited number of factors, thus they are not necessarily informative in other headache types. We report the psychometric properties of a new questionnaire, the Comprehensive Headache-related Quality of life Questionnaire (CHQQ) that may be more sensitive to the burden of headache. Patients and methods: A total of 202 patients suffering from migraine (n ¼ 168) or tension-type headache (TTH) (n ¼ 34) completed the CHQQ and SF-36, a generic QOL questionnaire. We assessed the reliability and validity of the CHQQ and its physical, mental and social dimensions. Results: The questionnaire was easy to administer. Reliability was excellent with Cronbach's alpha being 0.913 for the whole instrument (0.814-0.832 for its dimensions). The dimensions and total score showed significant correlations with the patients' headache characteristics (criterion validity), and were also significantly correlated with the SF-36 domains (convergent validity). The total score and dimensions were significantly (p < 0.005) lower in the migraine group than in the TTH group (discriminative validity). Conclusion: In this study the new headache-specific QOL instrument showed adequate psychometric properties.

Migraine is a common disabling neurovascular primary headache disorder. The pathomechanism is not clear, but extensive preclinical and clinical studies are ongoing. The structural basis of the leading hypothesis is the trigeminovascular... more

Migraine is a common disabling neurovascular primary headache disorder. The pathomechanism is not clear, but extensive preclinical and clinical studies are ongoing. The structural basis of the leading hypothesis is the trigeminovascular system, which includes the trigeminal ganglion, the meningeal vasculature, and the distinct nuclei of the brainstem, the thalamus and the somatosensory cortex. This review covers the effects of sensory (calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide and substance P), sympathetic (neuropeptide Y) and parasympathetic (vasoactive intestinal peptide) migraine-related neuropeptides and the functions of somatostatin, nociceptin and the orexins in the trigeminovascular system. These neuropeptides may take part in neurogenic inflammation (plasma protein extravasation and vasodilatation) of the intracranial vasculature and peripheral and central sensitization of the trigeminal system. The results of human clinical studies are discussed with regard to the alterations in these neuropeptides in the plasma, saliva and cerebrospinal fluid during or between migraine attacks, and the therapeutic possibilities involving migraine-related neuropeptides in the acute and prophylactic treatment of migraine headeache are surveyed.

Different classes of drugs, discovered by serendipity, have been used successfully for migraine prevention for more than 40 years. The progressive knowledge of migraine pathophysiology, brain hyperexcitability, and the specifi c... more

Different classes of drugs, discovered by serendipity, have been used successfully for migraine prevention for more than 40 years. The progressive knowledge of migraine pathophysiology, brain hyperexcitability, and the specifi c neurotransmitter systems involved in pain perception has driven the attempts at targeting two crucial mechanisms: the restoration of nociceptive dysmodulation and the inhibition of cortical hyperexcitability. The success of modern research trials with preventive migraine agents (mainly neuromodulators) and optimized treatment of acute attacks with drug combinations aimed at low serotonergic function, neurogenic infl ammation, and central sensitization has translated into better outcomes for patients and physicians. Trials combining preventive migraine agents with nonpharmacologic behavioral headache management have yielded additional benefi ts over either approach alone. With the clinical application of this updated information from clinical trials, migraine impact on productivity, quality of life, and suffering will certainly be diminished. We hope that these achievements will create a stable path of management to benefi t our patients, without interruption, into the foreseeable future.

Optometrists frequently encounter patients with migraine and patients and practitioners sometimes suspect that visual stimuli or visual anomalies trigger headaches. There is a lack of evidence-based research on the issue, however. Some... more

Optometrists frequently encounter patients with migraine and patients and practitioners sometimes suspect that visual stimuli or visual anomalies trigger headaches. There is a lack of evidence-based research on the issue, however. Some patients with migraine may be hypersensitive to visual stimuli, and it has been suggested that individually prescribed coloured filters might be an effective treatment to reduce symptoms from such stimuli. A recent randomised controlled trial showed such a treatment to be effective and the present paper reports on the optometric characteristics of the patients in this study. Twenty-one patients with neurologically diagnosed migraine were compared with 11 controls. No significant differences were found between the two groups with respect to refractive error, ocular pathology, colour vision, contrast sensitivity, accommodative function, strabismus and hyperphoria. The migraine group tended to be a little more exophoric, but by most criteria they were able to compensate for their exophoria as well as the control group. The migraine group were more prone to pattern glare than the controls (p ¼ 0.004). The effects of precision tinted and control tinted lenses were investigated. The only variable to show a consistent and marked improvement with tinted lenses was pattern glare. The most likely mechanism for the benefit from individually prescribed coloured filters in migraine is the alleviation of cortical hyperexcitability (Wilkins et al. 1994) and associated pattern glare.

BACKGROUND Primary headaches such as migraine and tension type headaches are extremely common and present a significant clinical challenge. These conditions involve a complex interaction between biological and psychological processes. As... more

BACKGROUND Primary headaches such as migraine and tension type headaches are extremely common and present a significant clinical challenge. These conditions involve a complex interaction between biological and psychological processes. As part of a "vicious cycle" effect, primary headaches can be deleterious to patients, causing stress, anxiety and catastrophization, while at the same time becoming exacerbated by those very same cognitive and emotional states. OBJECTIVES Medications often have a limited effect in treating chronic primary headache. Additionally, there are a number of sub-populations for whom many common medications are contraindicated, such as: pregnant women, patients with sensitivities to medication and patients in danger of medication overuse. Mind-body therapies for reducing stress, such as relaxation training and biofeedback, as well as cognitive and behavioral therapies have been used to treat primary headache for the better part of the last four decad...

The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as "reduced ability to work as usual", which do not capture at all the variety of... more

The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as "reduced ability to work as usual", which do not capture at all the variety of difficulties and the factors that impact over them. The aim of this paper is to present the validation of the HEADWORK questionnaire, which addresses the amount and severity of difficulties in work-related tasks and the factors that impact over them. We developed a set of items based on a previous literature review and patients' focus groups and tested it on a wide set of patients with episodic and chronic migraine attending eight different Italian headache centers. HEADWORK factor structure was assessed with exploratory and confirmatory factor analysis; internal consistency and construct validity were addressed as well. The validation sample (N = 373) was mostly composed of patients with episodic migraine without aura (64.3%) and of females (81%...

Missing meals and fasting have long been reported as headache triggers. Stress also has received attention for its role in precipitating headaches. This study explored the effects of eating behaviors on newonset headache. Analyzing only... more

Missing meals and fasting have long been reported as headache triggers. Stress also has received attention for its role in precipitating headaches. This study explored the effects of eating behaviors on newonset headache. Analyzing only the 1070 of 1648 (64.9%) diary days that followed a non-headache day, the study included 34 migraineurs who contributed a median (25th, 75th percentile) of 28 (22, 40) days of diary entries. Multivariable survival modeling with random effects was conducted, and hazards ratios and 95% confidence intervals were calculated. Nighttime snacking was associated with a 40% reduction in the odds of experiencing a headache compared to having no food (p = 0.013). Eating a late dinner was associated with a 21% reduction in the odds of headache when compared to no additional food, but this association was not statistically significant (p = 0. 22). These results demonstrate the potential for eating behaviors to be targeted in headache management, as regulated eating habits may have the potential to reduce the occurrence of headache. Although no causal relationship can be established, these results indicate that further research into the mechanisms of the association between eating behaviors and headache activity is warranted.