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Objective: This study was undertaken to identify magnetic resonance imaging (MRI) biomarkers that differentiate migraine from cluster headache patients and imaging features that are shared. Methods: Clinical, functional, and structural MRI data were obtained from 20 migraineurs, 20 cluster headache patients, and 15 healthy controls. Support vector machine algorithms and a stepwise removal process were used to discriminate headache patients from controls, and subgroups of patients. Regional between-group differences and association between imaging features and patients' clinical characteristics were also investigated. Results: The accuracy for classifying headache patients from controls was 80%. The classification accuracy for discrimination between migraine and controls was 89%, and for cluster headache and controls it was 98%. For distinguishing cluster headache from migraine patients, the MRI classifier yielded an accuracy of 78%, whereas MRI–clinical combined classification model achieved an accuracy of 99%. Bilateral hypothalamic and periaqueductal gray (PAG) functional networks were the most important MRI features in classifying migraine and cluster headache patients from controls. The left thalamic network was the most discriminative MRI feature in classifying migraine from cluster headache patients. Compared to migraine, cluster headache patients showed decreased functional interaction between the left thalamus and cortical areas mediating interoception and sensory integration. The presence of restlessness was the most important clinical feature in discriminating the two groups of patients. Interpretation: Functional biomarkers, including the hypothalamic and PAG networks, are shared by migraine and cluster headache patients. The thalamocortical pathway may be the neural substrate that differentiates migraine from cluster headache attacks with their distinct clinical features. ANN NEUROL 2023.

Since the high burden of chronic migraine (CM), it is challenging to identify the best prevention treatment. Based on the preclinical evidences about the different therapeutic targets of OnabotulinumtoxinA (BT-A), acting on C-fibers and anti-CGRP monoclonal antibodies (mAbs) acting on Aδ-fibers, the rationale of using as alternative or combining therapies has been hypothesized. Until now, the association of BT-A and mAbs has been poorly investigated. This study aimed to evaluate whether mAbs is effective and safe in CM patients previously treated with BT-A, either as alternative or add-on treatment. We enrolled 47 patients: according to the response to BT-A treatment, patients were defined Non-responder (NR) and Partial-responder (PR). NR were shifted to mAbs. PR were randomly divided into those who added mAbs therapy (PR-P) and those who shifted treatment (PR-S), interrupting BT-A. Clinical variables were collected at baseline, after three and six months. Study results evidenced the efficacy of mAbs in improving clinical outcomes in CM patients, with a better response in PR group. No statistically significant differences of clinical changes were observed between PR-P and PR-S groups. No safety concerns were raised in combined treatments. Preventive prophylaxis with mAbs is effective, even in difficult to treat CM patients. Further studies, with a larger sample size, are needed to highlight a potential additive effect of combined therapies.

Background Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. Methods A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. Results We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120 mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Conclusion Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention.

Background Monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients. Methods This observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO). Results We enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p Conclusion Migraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.

Objective To elucidate the hypothalamic involvement in episodic migraine and investigate the association between hypothalamic resting state functional connectivity changes and migraine patients’ clinical characteristics and disease progression over the years. Methods Ninety-one patients with episodic migraine and 73 controls underwent interictal resting state functional magnetic resonance imaging. Twenty-three patients and controls were re-examined after a median of 4.5 years. Hypothalamic resting state functional connectivity changes were investigated using a seed-based correlation approach. Results At baseline, a decreased functional interaction between the hypothalamus and the parahippocampus, cerebellum, temporal, lingual and orbitofrontal gyrus was found in migraine patients versus controls. Increased resting state functional connectivity between the hypothalamus and bilateral orbitofrontal gyrus was demonstrated in migraine patients at follow-up versus baseline. Migraine patients also experienced decreased right hypothalamic resting state functional connectivity with ipsilateral lingual gyrus. A higher migraine attack frequency was associated with decreased hypothalamic-lingual gyrus resting state functional connectivity at baseline, while greater headache impact at follow-up correlated with decreased hypothalamic-orbitofrontal gyrus resting state functional connectivity at baseline. At follow-up, a lower frequency of migraine attacks was associated with higher hypothalamic-orbitofrontal gyrus resting state functional connectivity. Conclusions During the interictal phase, the hypothalamus modulates the activity of pain and visual processing areas in episodic migraine patients. The hypothalamic-cortical interplay changes dynamically over time according to patients’ clinical features.

ObjectivesTo assess the effectiveness of Neuroaspis plp10 nutritional supplement when added to interferon (IFN)-β treatment in patients with relapsing-remitting multiple sclerosis (RRMS).DesignA 30-month phase III multicentre, randomised, double-blind, placebo-controlled trial. Randomisation stratified by centre using a computer-generated procedure with Neuroaspis plp10 versus placebo in 1:1 ratio. The first 6 months were used as both the pre-entry and normalisation period.Setting3 teaching hospitals in Greece and 1 Neurology Institute in Cyprus.Participants61 patients with RRMS on IFN-β were randomly assigned to receive Neuroaspis plp10 (n=32) or placebo (n=29), 20 mL, orally, once daily, for 30 months.InterventionNeuroaspis plp10, a cocktail mixture, containing specific PUFA (12 150 mg) and γ-tocopherol (760 mg) versus virgin olive oil (placebo).Main outcome measureThe primary end point was the annual relapse rate (ARR) whereas the secondary ones were the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale (EDSS) and the brain T2 and gadolinium-enhancing lesions, at 2 years.ResultsFor the intention-to-treat analyses Neuroaspis plp10 significantly reduced the ARR by 80%, (RRR, 0.20; 95% CI: 0.09 to 0.45; p=0.0001) and the risk of sustained progression of disability by 73% (HR, 0.27; 95% CI: 0.09 to 0.83; p=0.022) versus placebo, at 2 years. The number of T1 gadolinium-enhancing lesions and the number of new/enlarged T2-hyperintense lesions were significantly reduced (p=0.01 and pConclusionsNeuroaspis plp10 added to IFN-β was significantly more effective than IFN-β alone in patients with RRMS.Trial registration numberISRCTN06166891.

Background Several novel treatments targeting the calcitonin gene-related peptide pathway have been developed for migraine. We evaluated the efficacy of these medications, including atogepant, rimegepant, erenumab, eptinezumab, fremanezumab, and galcanezumab, for the prevention of migraine via network meta-analysis. Methods Databases, including MEDLINE via PubMed, EMBASE, and Cochrane central, were systematically reviewed, and all eligible phase 3 randomised controlled trials were included. Results Nineteen studies (n = 14,584 participants) were included. Studies included episodic (n = 11) and chronic (n = 4) migraine or both (n = 4). All interventions, except for eptinzumab 30 mg, significantly reduced mean monthly migraine days compared to placebo. All medications had a higher ≥50% responder rate than placebo and results were statistically significant in those with the subcutaneous or intravenous route of administrations, but not with the oral one. All medications significantly reduced mean monthly headache days, although no data for this outcome was available for rimegepant, and mean monthly acute medication days, with no data for eptinezumab. Conclusion The results show that medications targeting calcitonin gene-related peptide were effective in preventing migraine compared to placebo. Considering limitations of single studies, different populations such as episodic and chronic migraine, and the absence of head-to-head trials, all novel treatments decreased mean monthly migraine and headache days, and showed higher 50%, 75% and 100% responder rates than placebo. Trial registration: PROSPERO registration: CRD42022310579

To investigate in real-life the conversion from chronic migraine (CM) to episodic migraine (EM), specifically to EM with High-Frequency (HFEM: 8-14 monthly migraine days, MMDs), Medium-Frequency (MFEM, 4-7 MMDs), and Low-Frequency EM (LFEM, 0-3 MMDs), and its persistence during 1 year of treatment with galcanezumab.Consecutive CM patients treated with galcanezumab completing 1 year of observation were enrolled. We collected data on MMDs, pain intensity (Numeric Rating Scale, NRS score), and monthly acute medication intake (MAMI) from baseline (V1) to the 12-month visit (V12).Of the 155 enrolled patients, 116 (around 75%) reverted to EM at every visit and 81 (52.3%) for the entire 1-year treatment. Patients with older onset age (p = 0.010) and fewer baseline MMDs (p = 0.005) reverted more frequently to EM. At V12, 83 participants (53.5%) presented MFEM or LFEM. Patients reverted to MFEM or LFEM for 7 months (25th 1, 75th 11). The medication overuse discontinuation rate at V12 was 82.8% and occurred for 11 months (25th 8, 75th 12). From baseline to V12, the MAMI decreased by 17 symptomatic drugs (p 0.000001) while the NRS score reduced by almost 2 points (p 0.000001). A consistent transition to EM for the entire treatment year was observed in 81 (52.3%) patients.The 1-year GARLIT experience suggests that more than half of CM patients treated with galcanezumab persistently reverted to EM in real life.ClinicalTrials.gov NCT04803513.

Little research has investigated the experience of same-sex adoption from children's perspective. What does it feel like to be adopted by 2 dads or 2 moms? How do the challenges related to being adopted and the challenges related to growing up in a same-sex-parent family overlap in the identity construction of adoptees? This is the 1st European study giving voice to children adopted by same-sex couples focusing on their adoptive and family-related identities at four developmental stages: early childhood, middle childhood, preadolescence, and adolescence. In-depth interviews were conducted with a sample of 44 adoptees (36 males and 8 females; ages 3-18 years) and 62 adoptive parents (16 lesbian women and 46 gay men). Thematic analysis revealed that adoptees deal with unique developmental challenges connected to the intersection of both their adoptive and familial minority statuses. They often reported being confronted with heteronormative assumptions of family, which led them to question themselves regarding the way their family is perceived by others, to idealize the heteronuclear family form, and to increase their curiosity about their birth parents. Findings shed light on the evolution of adoptees' questions, feelings, and experiences related to their unique family arrangement from early childhood through adolescence, suggesting a better integration of their adoptive and minority group statuses at progressively more advanced developmental stages. Analyses underline the importance of open family communication for facilitating the integration of such complex elements in adoptees' emerging identity. Practice implications of the findings are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

In the last 20years, we observed significant improvements in the use of magnetic resonance imaging (MRI) for the evaluation of patients affected by migraine. Before these technological advances, knowledge of the pathogenesis of migraine was particularly based on clinical assessment. Complementary to clinical evaluation, conventional MRI provides both specific information for differential diagnosis (particularly if cortical or subcortical lesions are detected in the migrainous brain) and unsurpassable opportunities in migraine research. However, the correlations between brain structural and functional alterations and both the clinical manifestation of the disease and the individual history of the patient remains uncertain. Both quantitative and functional MR-based techniques have a great potential to better provide insights into human brain structures and possible links between brain areas and complex brain networks that could be involved in the pathophysiology of migraine. Morphometric and functional MRI approaches are contributing to better elucidate the mechanisms that underlie the pain mechanisms and functional adaptation in migraine patients. All these information support the view of migraine as a complex brain disorder involving different cortical and subcortical areas.

Tension-type headache (TTH) is the most prevalent neurological disorder worldwide and is characterized by recurrent headaches of mild to moderate intensity, bilateral location, pressing or tightening quality, and no aggravation by routine physical activity. Diagnosis is based on headache history and the exclusion of alternative diagnoses, with clinical criteria provided by the International Classification of Headache Disorders, third edition. Although the biological underpinnings remain unresolved, it seems likely that peripheral mechanisms are responsible for the genesis of pain in TTH, whereas central sensitization may be involved in transformation from episodic to chronic TTH. Pharmacological therapy is the mainstay of clinical management and can be divided into acute and preventive treatments. Simple analgesics have evidence-based effectiveness and are widely regarded as first-line medications for the acute treatment of TTH. Preventive treatment should be considered in individuals with frequent episodic and chronic TTH, and if simple analgesics are ineffective, poorly tolerated or contraindicated. Recommended preventive treatments include amitriptyline, venlafaxine and mirtazapine, as well as some selected non-pharmacological therapies. Despite the widespread prevalence and associated disability of TTH, little progress has been made since the early 2000s owing to a lack of attention and resource allocation by scientists, funding bodies and the pharmaceutical industry.

Tension-type headache (TTH) is the most prevalent neurological disorder worldwide and is characterized by recurrent headaches of mild to moderate intensity, bilateral location, pressing or tightening quality, and no aggravation by routine physical activity. Diagnosis is based on headache history and the exclusion of alternative diagnoses, with clinical criteria provided by the International Classification of Headache Disorders, third edition. Although the biological underpinnings remain unresolved, it seems likely that peripheral mechanisms are responsible for the genesis of pain in TTH, whereas central sensitization may be involved in transformation from episodic to chronic TTH. Pharmacological therapy is the mainstay of clinical management and can be divided into acute and preventive treatments. Simple analgesics have evidence-based effectiveness and are widely regarded as first-line medications for the acute treatment of TTH. Preventive treatment should be considered in individuals with frequent episodic and chronic TTH, and if simple analgesics are ineffective, poorly tolerated or contraindicated. Recommended preventive treatments include amitriptyline, venlafaxine and mirtazapine, as well as some selected non-pharmacological therapies. Despite the widespread prevalence and associated disability of TTH, little progress has been made since the early 2000s owing to a lack of attention and resource allocation by scientists, funding bodies and the pharmaceutical industry.

Randomized studies have reported a positive effect of candesartan, an angiotensin II receptor antagonist, in migraine prevention. The aim of our study was to explore patient subjective efficacy of candesartan in a real-world sample of migraine patients and try to identify predictors of candesartan response. We audited the clinical records of 253 patients who attended the King’s College Hospital, London, from February 2015 to December 2017, looking specifically at their response to candesartan. Univariate and multivariate logistic regression models were used to identify predictors of headache benefit. Odds ratios (OR) with confidence intervals (CI) 95% were calculated. Eighty-one patients (chronic migraine, n = 68) were included in the final analysis. Thirty-eight patients reported a positive response to candesartan, while 43 patients did not have a meaningful therapeutic effect. The median dose of candesartan was 8mg and the median treatment period was 6months. In a univariate logistic regression model, the presence of daily headache was associated with reduced odds of headache benefit (OR 0.39, 95% CI 0.16–0.96, p = 0.04). In multivariate logistic regression model, younger age (OR 0.92, 95% CI 0.87–0.98, p = 0.006) and longer disease duration (OR 1.06, 95% CI 1.01–1.12, p = 0.03) were associated with a good response to candesartan, while the presence of daily headache was associated with reduced odds of headache benefit (OR 0.16, 95% CI 0.04–0.71, p = 0.01). Having failed up to nine preventives in patients did not predict a treatment failure with candesartan as well. Candesartan yields clinical benefits in difficult-to-treat migraine patients, irrespective of previous failed preventives.

No psychological research has been done investigating the experiences of adoption by sexual minorities living in Europe. This qualitative study is the first cross-national research within the Europ...

Background and aims: Erenumab proved to be safe and well tolerated in a 5-year continuation of a 1-year double-blind, placebo-controlled study. Aim: to assess >48-week erenumab tolerability and safety in a real-world setting. Methods: In this long term (>48-week), multicenter (n = 15), longitudinal cohort real life study, we monitored all the adverse events emerged in consecutive adult patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) treated with monthly erenumab 70 mg or 140 mg from 20 December 2018 to 15 December 2020. Results: 442 patients (HFEM: 115;CM: 327) were treated with erenumab for >48 weeks: 209 (47.3%) patients were treated for 49–60 weeks, 132 (29.9%) for 61–72 weeks;73 (16.5%) for 73–84 weeks;21 (4.7%) for 85–100 weeks. Overall, >1 treatment emergent adverse event (TEAE) was reported by 136 (30.8%) [HFEM: 43 (37.4%);CM: 93 (28.4%)]. Most common TEAE were constipation (n = 66;14.9%), injection site erythema (n = 15;3.4%), and influenza (n = 7;1.6%). Serious adverse events (SAE) were reported by 8 patients (1.8%) and led to treatment discontinuation: severe constipation (n = 3), abdominal pain (n = 1), NSTEMI (n = 3), Covid-19 infection (n = 1). Only severe constipation was considered treatment-related SAE (0.45%). Conclusions: Conclusion: Erenumab is safe and well tolerated also in long-term treatment (>48 weeks) in real life.

Resting state (RS) functional connectivity (FC) abnormalities of brain networks involved in pain- and multisensory processing have been disclosed in adult-migraine patients. We explored RS FC of large-scale brain networks in pediatric-migraine patients and their correlation with patients' clinical characteristics. RS functional MRI data was acquired from 13 pediatric-migraine patients and 14 age- and sex-matched controls. Intra- and inter-network RS FC differences between patients and controls were evaluated. Correlations between RS FC abnormalities and patients' clinical characteristics were also assessed. Compared to controls, pediatric-migraine patients had a decreased RS FC of the left parieto-occipital junction of the default mode network (DMN) and left-dorsolateral prefrontal cortex of the executive control network (ECN). They also experienced an increased RS FC of the right frontopolar cortex of the right frontoparietal network (FPN) and the right-middle occipital gyrus of the secondary visual network. A significant stronger connectivity between the ECN and primary visual network and between the right FPN and primary sensorimotor, primary visual and auditory networks were found in migraine patients compared to controls. A significant weaker connectivity between the DMN and right FPN was revealed in migraineurs compared to controls. No correlation was found between intra- and inter-network RS FC abnormalities and patients' clinical characteristics. Pediatric-migraine patients harbor significant RS FC abnormalities in brain networks involved in multisensory processing and in the cognitive control of pain. An early dysregulation of multisensory processing, including pain, might represent a phenotypic biomarker of the disease.

The pathophysiology of vestibular migraine (VM) is at present poorly understood. Functional magnetic resonance imaging (fMRI), a technique that measures brain activity by detecting changes associated with blood flow oxygenation, has been used to study neural pathways involved in VM pathophysiology. In this study, we summarize results of previous fMRI studies in VM patients, both during and between vertigo attacks. Moreover, we report our experience in two patients with definite VM, who underwent fMRI during a visual stimulation in a vertigo-free period. Compared with 15 matched healthy controls, fMRI demonstrated activation of brain areas related to integration of visual and vestibular cues (increased activation of the paracentral lobule and bilateral inferior parietal lobule and decreased activation of the left superior frontal gyrus, head of the caudate nucleus, left superior temporal gyrus, left parahippocampal gyrus, and right lingual gyrus). Our results partially confirm those of other authors, reporting increased activation of multimodal association brain areas (BA 40, BA 31/5) and decreased activation of occipital regions In addition, we also found a decreased activation of fronto-temporal areas, such as the parahippocampal region, functionally involved in space memory and navigation.

BACKGROUND Change in lesion volume over time, measured on brain magnetic resonance imaging (MRI) scans, is an important outcome measure for natural history studies and clinical trials in multiple sclerosis (MS). PURPOSE To develop and test image analysis methods for quantification of lesion volume change in order to improve reliability. METHODS The technique is based on registration and subtraction, and was evaluated in a cohort of 20 MS patients with dual-echo images acquired annually over a period of four years. The study protocol was approved by the local ethics review boards of participating centers, and all subjects gave written informed consent. The repeatability was compared to that obtained by the standard method for obtaining lesion volume change by evaluating the total volume at each time point, and then subtracting the volumes to obtain the difference. RESULTS Compared to the standard method, the subtraction method had improved intrarater correlation (0.95 and 0.72 for the subtraction method and the standard method, respectively) and interrater correlation (0.51 and 0.28, respectively). Furthermore, the mean time required to analyze the scans from one patient was 41 minutes for the subtraction method compared to 125 minutes for the standard method. CONCLUSION Use of the subtraction algorithm leads to improved reliability and lower operator fatigue in clinical trials and studies of the natural history of MS.

Purpose of review Primary headaches, such as migraine and cluster headache, are one of the most common and disabling neurological diseases worldwide. Neuroimaging studies have changed the way we understand these diseases and have enriched our knowledge of the mechanisms of actions of currently available therapies. Recent findings The present review highlights the major findings reported in migraine and cluster headache neuroimaging over the last year. Widespread structural and functional abnormalities in cortical and subcortical areas involved in multisensory, including pain, processing have been shown in migraine and cluster headache patients during different phases of the disease. Beyond the involvement of single brain areas, dysfunctional brain networks contribute to their pathophysiology. New central mechanisms of action of headache preventive treatments have also been explored. Summary A better understanding of migraine and cluster headache biology has paved the way for the development of new improved treatments for both these conditions. Although significant advances have been made over the last year, there are still many unsolved questions to address.

Background A better understanding of the mechanisms underlying the migraine attack has reinforced the concept that migraine is a complex brain disease, and has paved the way for the development of new migraine specific acute treatments. In recent years, targeting the calcitonin gene-related peptide and its receptors has been one of the most promising pharmacological strategies for both acute and preventive treatment of migraine. Findings Randomized double-blind placebo-controlled trials have demonstrated the superiority of small molecule calcitonin gene-related peptide receptor antagonists (gepants) over placebo in treating acute migraine attacks measured as the two-hour pain free endpoint. Gepants also improved migraine associated symptoms, such as nausea, photophobia and phonophobia. Two of the class have had their development stopped because of hepatotoxicity, which is emerging as being due to metabolites. Gepants have a good tolerability and can be safely used in patients with stable cardiovascular disease. Conclusion Exciting results have been obtained targeting the calcitonin gene-related peptide pathway to abort acute migraine attacks, thus reinforcing the relevance of mechanism-based treatments specific for migraine.

ObjectiveTo explore cross-sectional and longitudinal gray matter (GM) volume changes in patients with migraine and their association with patients' clinical characteristics and disease activity.MethodsBrain T2-weighted and 3-dimensional T1-weighted scans were acquired from 73 episodic migraineurs and 46 age- and sex-matched nonmigraine controls at baseline. Twenty-four migraineurs and 25 controls agreed to be reexamined after a mean follow-up of 4 years. Using a general linear model and SPM12, a whole-brain analysis was performed to assess GM volume modifications.ResultsAt baseline, compared to controls, patients with migraine showed lower cerebellar GM volume and higher volume of regions of the frontotemporal lobes. At follow-up, migraineurs were significantly older than controls. Over the follow-up, migraineurs developed an increased volume of frontotemporoparietal regions, which was more prominent in patients with a higher baseline disease activity: long disease duration and high attack frequency. Migraineurs also developed decreased GM volume of visual areas, which was related to higher pain severity. Patients with an increased attack frequency at follow-up experienced both increased and decreased volume of nociceptive regions. In migraineurs, reduced GM volume of extrastriate visual areas during the follow-up was significantly correlated to baseline disease activity: shorter disease duration and lower attack frequency.ConclusionIn this cohort, the migraine brain changes dynamically over time, and different pathophysiologic mechanisms can occur in response to patients' disease severity. The interaction between predisposing brain traits and experience-dependent responses might vary across different nociceptive and visual areas, thus leading to distinct patterns of longitudinal GM volume changes.

Objective: Within the last decade, many changes have been made to the management of patients with multiple sclerosis (MS). The aim of our study was to investigate the global impact of all these changes on the disease's course. Materials and methods: This single-centre study was carried out on patients with multiple sclerosis (pwMS) who started treatment with first-line disease-modifying therapies. We have compared three large cohorts of patients with MS diagnosis, for three consecutive periods within July 2001, August 2001-December 2005, and January 2006-September 2011. Results: A total of 1068 relapsing-remitting pwMS cases were included. Patients in the last cohort began treatment earlier (P&nbsp

Purpose To characterize the spatial distribution of cervical cord T1-weighted hypointense lesions in patients with multiple sclerosis (MS) and analyze their association with cord atrophy and disability. Materials and Methods For this prospective study that took place between 2014 and 2016, 3.0-T high-resolution T1-weighted cervical cord magnetic resonance (MR) images and clinical evaluations were obtained from 82 patients with relapsing-remitting MS (RRMS), 33 patients with secondary progressive MS (SPMS), 25 patients with primary progressive MS (PPMS), and 35 sex-matched healthy control participants. Hypointense cord lesions on T1-weighted imaging were identified and corresponding lesion masks were produced. A semiautomatic method on the basis of active surfaces was used to perform voxel-wise assessment (by using statistical parametric mapping and full factorial models) of T1-weighted hypointense lesion distribution and cord atrophy. Results T1-weighted hypointense cervical cord lesions were detected in 122 of 140 (87.1%) patients with MS. Lesions were preferentially located in the posterior (P = .01) and upper (P < .001) cervical cord. Lesion extent at C1/C2 and C5 was higher in patient with SPMS versus RRMS, and patients with PPMS versus RRMS and SPMS (P value range