On the utility of the trail making test in migraine with and without aura: a meta-analysis.

This meta-analytical review assesses the utility of the Trail Making Test (TMT), versions A and B, in detecting migraine-related cognitive deficits. A comprehensive literature search was performed in two electronic databases and other sources to obtain relevant studies administering TMT to migraine patients. Search terms included "migraine" and "Trail Making". Only studies in which the TMT-A, TMT-B or both were administered to adult patients suffering from migraine with and without aura were included. All pooled meta-analyses were based on random effects models. A total of 14 studies for TMT-A and 15 for TMT-B met inclusion criteria and were subjected to meta-analyses. Results showed that performance is worse in migraine patients than in controls for both the TMT-A (Hedges' g = -.28) and TMT-B (g = -.37), with no difference between migraine with and without aura. This study demonstrates the sensitivity of the TMT in detecting cognitive alterations in migraine. This test should be considered for inclusion in cognitive batteries assessing patients with migraine.

Current understanding of premonitory networks in migraine: A window to attack generation.

AIM: To describe neuronal networks underlying commonly reported migraine premonitory symptoms and to discuss how these might precipitate migraine pain. BACKGROUND: Migraine headache is frequently preceded by a distinct and well characterized premonitory phase including symptoms like yawning, sleep disturbances, alterations in appetite and food intake and hypersensitivity to certain external stimuli. Recent neuroimaging studies strongly suggest the hypothalamus as the key mediator of the premonitory phase and also suggested alterations in hypothalamic networks as a mechanism of migraine attack generation. When looking at the vast evidence from basic research within the last decades, hypothalamic and thalamic networks are most likely to integrate peripheral influences with central mechanisms, facilitating the precipitation of migraine headaches. These networks include sleep, feeding and stress modulating centers within the hypothalamus, thalamic pathways and brainstem centers closely involved in trigeminal pain processing such as the spinal trigeminal nucleus and the rostral ventromedial medulla, all of which are closely interconnected. CONCLUSION: Taken together, these networks represent the pathophysiological basis for migraine premonitory symptoms as well as a possible integration site of peripheral so-called "triggers" with central attack facilitating processes.

Acquired equivalence and related memory processes in migraine without aura.

Introduction Interictal deficits of elementary visuo-cognitive functions are well documented in patients with migraine and are mostly explained in terms of neocortical hyperexcitability. It has been suggested that the basal ganglia and the hippocampi might also be affected in migraine. If so, a deterioration of learning and memory processes related to these structures is expected. Methods A visual learning paradigm thought to be capable of dissociating learning/memory processes mediated by the basal ganglia from processes mediated by the hippocampus (the Rutgers Acquired Equivalence Test) was applied to a group of patients with migraine without aura and to age- and sex-matched controls. Results Patients with migraine showed a significantly poorer performance in both main phases of the test and the deficit in the phase considered to be dependent on the hippocampi was especially marked. Conclusions These results can be interpreted as behavioural support for findings that have suggested the involvement of the basal ganglia and the hippocampi in migraine, but further research is needed to clarify these findings.

Auditory Processing in Children with Migraine: A Controlled Study.

Background This study aimed to investigate central auditory processing performance in children with migraine and compared with controls without headache. Methods Twenty-eight children of both sexes, aged between 8 and 12 years, diagnosed with migraine with and without aura, and a control group of the same age range and with no headache history, were included. Gaps-in-noise (GIN), duration pattern test (DPT), synthetic sentence identification (SSI) test, and nonverbal dichotic test (NVDT) were used to assess central auditory processing performance. Results Children with migraine performed significantly worse in DPT, SSI test, and NVDT when compared with controls without headache; however, no significant differences were found in the GIN test. Conclusions Children with migraine demonstrate impairment in the physiologic mechanism of temporal processing and selective auditory attention. In our short communication, migraine could be related to impaired central auditory processing in children.

Raven coloured progressive matrices in migraine without aura patients.

Conflicting results emerged from studies investigating cognitive performances in migraine patients. Based on clinical and neuroradiological aspects, the possible involvement of executive functions has been especially taken into consideration. The aim of this study was to evaluate, in a population of subjects affected by migraine without aura (MwoA), frontal lobe cognitive functions. We enrolled all the consecutive patients affected by MwoA referred to our headache centre for a first evaluation. Each patient underwent a neuropsychological evaluation including Raven coloured progressive matrices (CPM). We collected variables as age, education, years of migraine, frequency of attacks and CPM scores. Relationship between continuous variables was explored with multiple regression lines, selecting the best-fitting trendline for each relationship. We obtained a final sample of 36 subjects (females: 62.5%; mean age: 42.25 ± 10.21 years). Patients had mean length of migraine history of 12.25 ± 11.00 years and a mean frequency of attacks of 8.06 ± 7.15 per month. Linear regression underlines a progressive decrease of CPM score with the increase of the migraine history's length (R 2 = 0.8871; p < 0.001), and the frequency of migraine attacks (R 2 = 0.3122; p < 0.05). Our findings suggest that pathological CPM scores can be associated with the severity of migraine. These data seem to confirm the hypothesis of an impairment of executive functions in MwoA. Different hypotheses to explain cognitive impairment in migraine have been postulated including the impact of the typical white matter lesions and a long history of drug abuse. The possible relevant clinical consequence of a full comprehension of this particular aspect related to migraine deserves further attention and consideration.

The role of attachment insecurity in the emergence of anxiety symptoms in children and adolescents with migraine: an empirical study.

BACKGROUND: It is widely recognised that there are associations between headache, psychiatric comorbidity and attachment insecurity in both adults and children. The aims of this study were: 1) to compare perceived attachment security and anxiety in children and adolescents with migraine without aura and a healthy control group; 2) to test whether the child's perceived security of attachment to the mother and the father mediated the association between migraine and anxiety. METHODS: One hundred children and adolescents with Migraine without Aura were compared with a control group of 100 children without headache. The Security Scale (measures perceived security of attachments) and the Self-Administered Psychiatric Scales for Children and Adolescents, a measure of anxiety symptoms, were administered to all participants. RESULTS: The clinical group had lower attachment security than the control group and higher scores on all anxiety scales. Anxiety was negatively correlated with attachment. Children's attachment to their mother mediated the increase in global anxiety in the clinical group. Insecure paternal attachment was associated with greater insecurity in maternal attachment, suggesting that there is a complex pathway from migraine to anxiety symptoms mediated by perceived insecurity of paternal attachment and hence also by perceived insecurity of maternal attachment. CONCLUSION: These results suggest that insecure parental attachment may exacerbate anxiety in children and adolescents with migraine and point to the importance of multimodal interventions, perhaps taking account of family relationships, for children and adolescents with migraine.

Assessment of gray and white matter structural alterations in migraineurs without aura.

BACKGROUND: Migraine constitute a disorder characterized by recurrent headaches, and have a high prevalence, a high socio-economic burden and severe effects on quality of life. Our previous fMRI study demonstrated that some brain regions are functional alterations in migraineurs. As the function of the human brain is related to its structure, we further investigated white and gray matter structural alterations in migraineurs. METHODS: In current study, we used surface-based morphometry, voxel-based morphometry and diffusion tensor imaging analyses to detect structural alterations of the white matter and gray matter in 32 migraineurs without aura compared with 32 age- and gender-matched healthy controls. RESULTS: We found that migraineurs without aura exhibited significantly increased gray matter volume in the bilateral cerebellar culmen, increased cortical thickness in the lateral occipital-temporal cortex, decreased cortical thickness in the right insula, increased gyrification index in left postcentral gyrus, superior parietal lobule and right lateral occipital cortex, and decreased gyrification index in the left rostral middle frontal gyrus compared with controls. No significant change in white matter microstructure was found in DTI analyses. CONCLUSION: The significantly altered gray matter brain regions were known to be associated with sensory discrimination of pain, multi-sensory integration and nociceptive information processing and were consistent with our previous fMRI study, and may be involved in the pathological mechanism of migraine without aura.

Cognitive dysfunctions and psychological symptoms in migraine without aura: a cross-sectional study.

BACKGROUND: The occurrence of cognitive dysfunctions and psychological symptoms, as well as their mutual relationships, in migraine patients are still debated. The aim of the study was to characterize the cognitive profile and psychological symptoms (i.e. depression, anxiety and apathy) in drug-naïve migraine without aura (MwoA) patients. METHODS: Seventy-two consecutive MwoA patients, referred to the Italian University Headache Clinic and 72 healthy subjects (HCs) were enrolled. Patients, during an attack-free period, and HCs completed Montreal Cognitive Assessment (MoCA), Beck Depression Inventory-II (BDI-II), Self-version of Apathy Evaluation Scale (AES-S) and State and Trait Anxiety Inventory (STAI-Y-1 and 2). Clinical parameters of disease severity (i.e. disease duration, migraine attacks per month, mean pain intensity during migraine attacks, migraine disability and impact on daily life) were recorded. RESULTS: Although performance of MwoA patients on MoCA was above Italian cut-off threshold (<15.5) suggesting presence of cognitive impairment, MwoA patients achieved significantly lower scores than HCs on total MoCA scale (22.3 ± 2.7 versus 25.4 ± 2.3) and on its attention (4.9 ± 1.1 versus 5.6 ± 0.7), memory (1.8 ± 1.4 versus 3.1 ± 1.3), visuospatial (3.2 ± 0.9 versus 3.6 ± 0.6) and executive subscales (2.6 ± 1.1 versus 3.1 ± 0.8). In addition, we observed significant correlations between MoCA executive domain subscore and the attack-related disability score (MIDAS). As for behavioral profile, the percentage of depressive symptoms (4.2 %), high state and trait anxiety (13.9 and 9.7 %, respectively), and apathy (11.1 %) in MwoA patients were similar to that of HCs. No significant associations of behavioural symptoms with cognitive performance and clinical parameters were found. CONCLUSIONS: Drug-naïve MwoA patients are characterized by subtle cognitive dysfunctions and low percentage of behavioural symptoms. The results support the importance of searching for subclinical cognitive disturbances in patients with MwoA, who deserve to be followed-up to verify whether they develop clinically relevant disorders over time.

Genetic contribution of catechol-O-methyltransferase in hippocampal structural and functional changes of female migraine sufferers.

Physiological and emotional stressors are associated with or provoke each migraine attack and cause structural and functional changes in the central nervous system. The hippocampus, a limbic structure important in anxiety-related behavior, is vulnerable to long-term stress. Given that catechol-O-methyltransferase (COMT) is widely distributed in the hippocampus and its genetic variation is thought to contribute to the interindividual variability in pain perception and anxiety regulation, whether or not migraine and COMT val(158) met genotype have an interactive effect in the key brain area related to maladaptive stress, the hippocampus, is still poorly understood. Using T1-weighted and resting functional MRI, we evaluated the effect of COMT genetic variations on migraine and possible interactions between COMT and the disease in brain structure and function in 135 females with migraine without aura (MWoA) and 111 matched health controls (HC). Optimized voxel-based morphometry (VBM) and functional connectivity (FC) analyses were applied. From the whole brain VBM analysis, we found a significant disease × genotype interaction in the hippocampus, which overlapped with disease-related increase of gray matter (GM) in val homozygote migraineurs. In our results, increased GM in the hippocampus was only found in val homozygote MWoA compared to val homozygote HC. Moreover, FC between the hippocampus and the medial prefrontal cortex was significantly decreased in val homozygotes, and it was negatively correlated with self-rating anxiety scale values.Our results indicated that brain structure and function of the hippocampus are differentially affected by migraine in val homozygotes compared with met carriers.

Cognitive dysfunction during migraine attacks: a study on migraine without aura.

BACKGROUND: Cognitive difficulties contribute to patients' disability during migraine attacks and have been overlooked in migraine research. Neuropsychological studies performed during attacks have produced inconsistent findings due to design differences and limitations. OBJECTIVE: Our objective is to document changes in cognitive performance of migraine patients during migraine attacks with a comprehensive battery of cognitive/behavioral tests, while controlling for potential confounders. METHOD: A prospective two-period, randomized, cross-over study compared within-subject neuropsychological evaluation in two conditions-during a naturally occurring untreated migraine attack and a headache-free period. RESULTS: Thirty-nine patients with episodic migraine (37 females, average 38 years old) were included and 24 completed the study. Participants performed worse during the attack in the majority of cognitive tests, compared to the headache-free status, and significantly so in word reading speed (p = 0.013), verbal learning (p = 0.01), short-term verbal recall with (p = 0.01) and without (p = 0.013) semantic cueing and delayed recall with (p = 0.003) and without (p = 0.05) semantic cues. Differences found were unrelated to age, gender, literacy, condition order, interval between evaluations, anxiety, pain intensity or duration of the attack. DISCUSSION: Cognitive performance decreases during migraine attacks, especially in reading and processing speed, verbal memory and learning, supporting patients' subjective complaints. These findings suggest the existence of a reversible brain dysfunction during attacks of migraine without aura, which can relate specifically to migraine or be a consequence of acute pain processing by the brain.

Health state utilities for migraine based on attack frequency: a time trade-off study.

This study aims to evaluate health state utilities for migraine based on attack frequency from a mixed population sample consisting of migraineurs and non-migraineurs. A cross-sectional questionnaire survey was designed to measure health-related quality of life (HRQOL) in migraine without aura by time trade-off method (TTO). A convenience sample of university students and staff was recruited regardless of having ever experienced migraine or not. Subjects were asked to elicit two hypothetical health states characterised by different migraine frequencies ('m': two migraines lasting 4 h each month and 'w': each week) within two hypothetical lifetime frames (20 years left to live/lives until the age of 80 years). Utilities were calculated for the four tasks (U20m, U80m, U20w, U20w) and compared amongst subgroups. Overall 180 respondents were included in the analysis. Mean age was 25.6 years (SD 6.4), 128 (71%) were female and 110 (61%) were self-reported migraineurs. Mean utilities for two migraines each month were U20m = 0.84 (SD 0.26) and U80m = 0.89 (SD 0.14), and for each week were U20w = 0.79 (SD 0.27) and U80w = 0.83 (SD 0.17), respectively. Self-reported migraineurs and females attached higher mean utilities for U80m and older respondents for U20m, respectively (p < 0.05). To our knowledge, this is the first study that provides HRQOL results measured by TTO methodology for migraine. Utility loss ranged from 0.1 to 0.2 depending on attack frequency. HRQOL impairment of having two migraine attacks per week was found similar to living with low back pain (0.77-0.79).

Executive dysfunctions in migraine with and without aura: what is the role of white matter lesions?

OBJECTIVE/BACKGROUND: Executive dysfunctions and white matter lesions on magnetic resonance imaging have been reported in migraine. The aim of this study was to determine whether any correlation between these 2 variables exists. MATERIALS AND METHODS: Forty-four subjects affected by migraine with or without aura were compared with 16 healthy subjects. A battery of neuropsychological tests assessing executive functions was administered to all subjects. Number and total volume of white matter lesions were assessed in the whole brain and in the frontal lobe. RESULTS: The performances of both groups of migraineurs, with and without aura, were significantly worse when compared with controls on Boston Scanning Test. Moreover, we found lower performances compared with controls respectively on Frontal Assessment Battery in patients with migraine with aura and on Controlled Oral Word Association Test in patients with migraine without aura. Nineteen patients (43.2%) and one control subject (6.2%) had white matter lesions. We did not find any significant correlation between white matter lesions load and neuropsychological performances. CONCLUSIONS: On the basis of our results, white matter lesions load on magnetic resonance imaging do not seem to contribute to neuropsychological performances deficit in migraineurs.

Higher burden of migraine compared to other neurological conditions: results from a cross-sectional study.

Headache disorders are prevalent, burdensome and costly. However, it is difficult to get an idea of how much of a burden do they cause if they are not compared with other conditions. Using data from PARADISE project, we compared 80 migraineurs and 80 patients similar for age, gender and work condition. Our results showed that the amount of psycho-social difficulties was higher among patients with migraine than among patients with epilepsy, stroke, multiple sclerosis or Parkinson's disease.

Alexithymia and its impact on quality of life in a group of Brazilian women with migraine without aura.

BACKGROUND: Migraine is a type of primary headache widely known for its impact on quality of life of patients. Although the psychological aspects of the disease are receiving increasing attention in current research, some of them, as alexithymia, are still seldom explored. This study aimed to provide evidence on the relationships between markers of depression, anxiety, alexithymia, self-reflection, insight and quality of life in migraine. METHODS: Forty female outpatients from a Brazilian specialized headache hospital service and a paired control group were compared. RESULTS: The results revealed that women with migraine had higher levels of depression, anxiety and alexithymia, and lower levels of quality of life, self-reflection and insight, compared to controls. Quality of life in women with migraine was predicted by levels of depression and one alexithymia factor (ability to express emotions and fantasies). A binary regression analysis between clinical and control groups revealed the migraine group to comprise individuals with high anxiety, low quality of life in the physical domain and the presence of a concrete thinking style. CONCLUSIONS: The results highlight the relevance of considering psychological variables in the routine healthcare practices for migraine patients in general, while keeping steady attention to individual case features.

Disrupted default mode network connectivity in migraine without aura.

BACKGROUND: Resting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated disrupted default mode network (DMN) connectivity in a number of pain conditions, including migraine. However, the significance of altered resting-state brain functional connectivity in migraine is still unknown. The present study is aimed to explore DMN functional connectivity in patients with migraine without aura (MwoA) and investigate its clinical significance. METHODS: To calculate and compare the resting-state functional connectivity of the DMN in 20 patients with MwoA, during the interictal period, and 20 gender- and age-matched HC, Brain Voyager QX was used. Voxel-based morphometry was used to assess whether between-group differences in DMN functional connectivity were related to structural differences. Secondary analyses explored associations between DMN functional connectivity, clinical and neuropsychological features of migraineurs. RESULTS: In comparison to HC, patients with MwoA showed decreased connectivity in prefrontal and temporal regions of the DMN. Functional abnormalities were unrelated to detectable structural abnormalities or clinical and neuropsychological features of migraineurs. CONCLUSIONS: Our study provides further evidence of disrupted DMN connectivity in patients with MwoA. We hypothesize that a DMN dysfunction may be related to behavioural processes such as a maladaptive response to stress which seems to characterize patients with migraine.

Executive resting-state network connectivity in migraine without aura.

BACKGROUND: Converging neuropsychological evidence suggests that in migraine executive functions (EF) may be affected during interictal periods. OBJECTIVE: To evaluate the functional connectivity of the fronto-parietal networks (FPN) known to be associated with EF, in migraine without aura (MwoA) patients, in the interictal period, in comparison to healthy controls (HC). METHODS: Using resting-state functional MRI (RS-fMRI), we compared functional connectivity within the FPN in 14 patients with MwoA versus 14 sex- and age-matched HC, and assessed the correlation between functional connectivity within FPN, clinical features of MwoA patients, and EF. We used voxel-based morphometry to assess whether between-group differences in functional connectivity were dependent on structural differences. RESULTS: Neuropsychological data revealed no significant executive dysfunction in MwoA patients. RS-fMRI showed that MwoA patients, compared to HC, had significant functional connectivity reduction within the right FPN and specifically in the middle frontal gyrus (MFG) and the dorsal anterior cingulate cortex. In addition, we found that MFG reduced connectivity was negatively correlated with the pain intensity of migraine attacks. There were no structural differences between the two groups. CONCLUSIONS: Our data suggest that, even in the absence of clinically evident EF deficits, MwoA is associated with reduced FPN functional connectivity. This study provides further insights into the complex scenario of migraine mechanisms.

Clinical correlates and diagnostic utility of osmophobia in migraine.

BACKGROUND: Osmophobia is an under-investigated associated symptom in migraine. OBJECTIVE: To evaluate the clinical correlates and diagnostic utility of osmophobia. METHODS: Adult patients with migraine (with or without aura), probable migraine (PM), tension-type headache (TTH), and cluster headache (CH) were recruited retrospectively from our headache registration system. Migraine patients with and without osmophobia were compared. The newly proposed criteria for migraine requiring at least two of photo-, phono-, or osmophobia instead of both photo- and phonophobia were validated. RESULTS: In total, 2883 patients were included: 1809 migraine, 792 PM, 138 TTH, and 144 CH. Osmophobia was more common in migraine (62.2%) than in PM (33.8%), TTH (14.5%), and CH (31.3%) (all p < 0.001). Migraine patients with osmophobia scored higher on the Hospital Anxiety and Depression Scale (HADS) than those without (15.6 ± 7.6 vs. 13.3 ± 7.8, p < 0.001). The concordance in headache diagnoses between ICHD-2 (International Classification of Headache Disorders, Second Edition) and the newly proposed criteria was "almost perfect" (κ = 0.886, p < 0.001). Additionally, 16.9% of ICHD-2 PM patients were reclassified as migraine using the newly proposed criteria. CONCLUSIONS: Osmophobia was prevalent in migraineurs, and was associated with higher HADS scores. The newly proposed criteria appear comparable to the ICHD-2 criteria, and may increase the diagnostic yield for Asian migraineurs, among whom photophobia was less common.

The effectiveness of a group-based acceptance and commitment additive therapy on rehabilitation of female outpatients with chronic headache: preliminary findings reducing 3 dimensions of headache impact.

OBJECTIVE: Examine whether acceptance and commitment additive therapy is effective in reducing the experience of sensory pain, disability, and affective distress because of chronic headache in a sample of outpatient Iranian females. BACKGROUND: Chronic headaches have a striking impact on sufferers in terms of pain, disability, and affective distress. Although several Acceptance and Commitment Therapy outcome studies for chronic pain have been conducted, their findings cannot be completely generalized to chronic headaches because headache-related treatment outcome studies have a different emphasis in both provision and outcomes. Moreover, the possible role of Iranian social and cultural contexts and of gender-consistent issues involved in Acceptance and Commitment Therapy outcomes deserve consideration. METHODS: This study used a randomized pretest-post-test control group design. The sample was selected from consecutive female outpatients with chronic headache, attending and/or referred to a headache clinic in a governmental hospital from April 2011 to June 2011. In total, 80 female outpatients were interviewed, and after implementing inclusion/exclusion criteria, thirty females were considered eligible to participate in the study. Half (n = 15) were randomly selected to participate in the treatment group. Four participants of this group failed to complete the treatment sessions (n = 11). The Acceptance and Commitment Therapy group received the medical treatment as usual and 8 sessions of Acceptance and Commitment Therapy. The other half (n = 15) served as the control group that received only medical treatment as usual. The short form of McGill pain questionnaire, the migraine disability assessment scale, and the trait subscale of the state-trait anxiety inventory were administered, which operationalized 3 dimensions of impact of chronic headache, sensory pain, disability, and emotional distress, respectively, to explore the impact of recurrent headache episodes. Pretest and post-test measures on these 3 dimensions of impact were the primary outcome measures of this study. Analyses of covariance with the pretreatment score used as a covariate were conducted on pain intensity, degree of disability, and level of affective distress before and after therapy to assess therapeutic intervention effectiveness. RESULTS: Chronic tension type of headache (63%) and chronic migraine without aura (37%) were the headache types reported by the participants. Data analyses indicated the significant reduction in disability (F[1,29] = 33.72, P < .0001) and affective distress (F[1,29] = 28.27, P < .0001), but not in reported sensory aspect of pain (F[1,29] = .81, P = .574), in the treatment group in comparison with the control group. CONCLUSIONS: The effectiveness of a brief acceptance and commitment additive therapy in the treatment of Iranian outpatient females with chronic headache represents a significant scientific finding and clinical progress, as it implies that this kind of treatment can be effectively delivered in a hospital setting.

Prevalence and impact of headache and migraine among secondary school students in Nigeria.

BACKGROUND: A cross-sectional descriptive study to determine the overall, age and gender specific prevalence, trigger factors and impact of headache and migraine on quality of life of students attending secondary schools in Benin City, Nigeria. METHODS: Six secondary schools were randomly selected from which students were randomly selected. A self-administered questionnaire was used to screen those with frequent headache, defined as at least 2 episodes of headache unrelated to fever or any underlying disease within the last 12 months or at least 1 episode in the last 6 months preceding the date questionnaire was administered. Another questionnaire based on the ICHD-2 criteria for diagnosis of migraine was then administered to those with frequent headaches. Data analysis was with SPSS 13.0 for Windows. RESULTS: One thousand six hundred and seventy-nine students aged 11-18 years were recruited. The overall prevalence of headache was 19.5%. The prevalence of migraine was 13.5%. Migraine was more common in girls than in boys at all ages. The most common trigger factors included emotional stress, sunlight or bright light, sleep deprivation, and hunger. Inability to participate in outdoor activities, household chores, and school absenteeism were the common impacts on the quality of life of among 76.8% of the migraineurs. CONCLUSION: Migraine is common and underdiagnosed among secondary school students in Benin City, Nigeria, and negatively impacts on the quality of life including school absenteeism.