Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: A Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited. The aim of this study is to compare clinical presentations and outcomes between the 2 groups. METHODS: A retrospective multicenter cohort study included patients with PML from 2009 to 2022 treated with S1P-RMs or natalizumab. Data on clinical and radiologic presentation, outcomes, immune reconstitution inflammatory syndrome (IRIS), survival, disability (using the modified Ranking scale-mRS), and MS relapses post-PML were analyzed. RESULTS: Of 88 patients, 84 were analyzed (20 S1P-RM, 64 natalizumab). S1P-RM-associated PML was diagnosed in older patients (median age 52 vs 44 years, p < 0.001) and after longer treatment duration (median 63.9 vs 40 months, p < 0.001). Similarly, S1P-RM patients were more prone to show symptoms at diagnosis (100 vs 80.6%, p = 0.035), had more disseminated lesions (80% vs 34.9%, p = 0.002), and had higher gadolinium enhancement (65% vs 39.1%, p = 0.042). Natalizumab patients had a higher IRIS development rate (OR: 8.3 [1.92-33.3]). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, post-treatment MS activity was higher in S1P-RM cases (OR: 5.7 [1.4-22.2]). DISCUSSION: S1P-RM-associated PML shows reduced IRIS risk but higher post-treatment MS activity. Clinicians should tailor post-PML treatment based on pre-PML medication.

Neuropathic pain: Evidence based recommendations.

Neuropathic pain continues to be a significant problem that lacks effective solutions for every single patient. In 2015, international guidelines (NeuPSIG) were published, while the French recommendations were updated in 2020. The purpose of this minireview is to provide an update on the process of developing evidence-based recommendations and explore potential changes to the current recommendations. Primary treatments for neuropathic pain include selective serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine, gabapentin, tricyclic antidepressants, as well as topical lidocaine and transcutaneous electrical nerve stimulation, which are specifically suggested for focal peripheral neuropathic pain. Pregabalin is a first line treatment according to international guidelines but second-line in the more recent French guidelines, due to lower efficacy seen in more recent studies and misuse risk. Additionally, tramadol, combination therapies, and psychotherapy as adjuncts are proposed second line; high-concentration capsaicin patches, and botulinum toxin A are proposed specifically for focal peripheral neuropathic pain. In cases where primary and secondary treatments prove insufficient, third-line options come into play. These include high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the motor cortex, spinal cord stimulation, and the use of strong opioids when no alternative is available. To ensure optimal management of neuropathic pain in real-life situations, it is imperative to disseminate these recommendations widely and secure the acceptance of practitioners. By doing so, we can bridge the gap between theory and practice, and enhance the overall care and treatment of individuals suffering from neuropathic pain.

Multiple Sclerosis-Associated Uveitis: A Case Report of Refractory Bilateral Chronic Granulomatous Panuveitis Successfully Treated with Tocilizumab.

PURPOSE: To report a case of uveitis associated with multiple sclerosis (MS) that was refractory to multiple lines of therapy but achieved remission with tocilizumab. METHODS: We conducted a retrospective analysis of the patient's medical record including clinical, biological and imaging data. RESULTS: A 33-year-old female patient with a history of MS inactive for 5 years on teriflunomide, and no significant medical or ophthalmological history, presented with bilateral granulomatous panuveitis. Initial examination revealed a visual acuity of 0.4 logMAR and 1.3 logMAR in the right eye and the left eye, respectively, along with a significant anterior chamber flare in both eyes, posterior synechiae, large granulomatous keratic precipitates, bilateral vitritis, bilateral macular edema with foveolar pigment epithelial detachment, and significant bilateral venous and arterial vasculitis. The patient underwent several lines of treatment, all of which proved unsuccessful, including corticosteroids alone or in combination with azathioprine, methotrexate, and mycophenolate mofetil. As a final therapeutic option, tocilizumab was initiated, leading to the remission of uveitis. One year later, the uveitis remained inactive under a 5 mg/day prednisone regimen. CONCLUSIONS: Tocilizumab appears to be an efficient option for managing uveitis associated with MS and may be a valuable choice for clinicians dealing with such cases.

Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society.

BACKGROUND: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk. OBJECTIVE: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS). METHODS: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal. RESULTS: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations. CONCLUSION: These recommendations propose a strategic approach to managing cancer risk in PwMS.

Pain in Parkinson disease: mechanistic substrates, main classification systems, and how to make sense out of them.

ABSTRACT: Parkinson disease (PD) affects up to 2% of the general population older than 65 years and is a major cause of functional loss. Chronic pain is a common nonmotor symptom that affects up to 80% of patients with (Pw) PD both in prodromal phases and during the subsequent stages of the disease, negatively affecting patient's quality of life and function. Pain in PwPD is rather heterogeneous and may occur because of different mechanisms. Targeting motor symptoms by dopamine replacement or with neuromodulatory approaches may only partially control PD-related pain. Pain in general has been classified in PwPD according to the motor signs, pain dimensions, or pain subtypes. Recently, a new classification framework focusing on chronic pain was introduced to group different types of PD pains according to mechanistic descriptors: nociceptive, neuropathic, or neither nociceptive nor neuropathic. This is also in line with the International Classification of Disease-11 , which acknowledges the possibility of chronic secondary musculoskeletal or nociceptive pain due to disease of the CNS. In this narrative review and opinion article, a group of basic and clinical scientists revise the mechanism of pain in PD and the challenges faced when classifying it as a stepping stone to discuss an integrative view of the current classification approaches and how clinical practice can be influenced by them. Knowledge gaps to be tackled by coming classification and therapeutic efforts are presented, as well as a potential framework to address them in a patient-oriented manner.

[Anti-calcitonin generelated peptide (CGRP) therapies for migraine]. / Anticorps anti-CGRP et migraine.

ANTI-CALCITONIN GENE-RELATED PEPTIDE (CGRP) THERAPIES FOR MIGRAINE. Currently, four monoclonal antibodies targeting the CGRP (calcitonin gene-related peptide) pathway have been shown to be effective as migraine prophylactics: eptinezumab, erenumab, fremanezumab and galcanezumab. Unlike the usual preventive treatments, they are administered parenterally: subcutaneously (monthly or quarterly) or by quarterly IV infusion for eptinezumab. They reduce the frequency of attacks by at least 50% in 50 to 60% of migraine patients, even in cases of failure of several conventional preventive treatments, in cases of chronic migraine and medication overuse. Their tolerance is better than that of conventional oral treatments and the discontinuation rates are very low. They can be proposed after failure of at least two conventional prophylactic treatments, in patients with at least 8 migraine days per month and without cardiovascular pathology. Indeed, these drugs present a risk in case of cardiovascular disease, by inhibiting vasodilation, and are therefore contraindicated in this population. The main limitation to the use of these treatments in France at present is the lack of reimbursement, the cheapest molecule being available at a price of 245 € per injection.

ANTICORPS ANTI-CGRP ET MIGRAINE. Actuellement, quatre anticorps monoclonaux ciblant la voie du CGRP (calcitonin gene-related peptide) ont démontré une efficacité en tant que traitement prophylactique de la migraine : l'eptinézumab, l'érénumab, le frémanézumab et le galcanézumab. À la différence des traitements préventifs habituels, ils sont administrés par voie parentérale : voie sous-cutanée (mensuelle ou trimestrielle) ou perfusion intraveineuse trimestrielle pour l'eptinézumab. Ils permettent de réduire la fréquence des crises d'au moins 50 % chez 50 à 60 % des patients migraineux, même en cas d'échec de plusieurs traitements de fond classiques, en cas de migraine chronique et d'abus médicamenteux. Leur tolérance est meilleure que celle des traitements oraux classiques et les taux d'arrêt sont très faibles. Ils peuvent être proposés après échec d'au moins deux traitements prophylactiques classiques chez des patients ayant au moins huit jours de migraine par mois et sans pathologie cardiovasculaire. En effet, ces médicaments inhibent la vasodilatation et présentent donc un risque en cas de maladie cardiovasculaire ; ils sont ainsi contre-indiqués dans cette situation. La principale limite à leur utilisation à l'heure actuelle en France est l'absence de remboursement, la molécule la moins chère étant disponible au prix de 245 € par injection.

Pregnancy and multiple sclerosis: 2022 recommendations from the French multiple sclerosis society.

OBJECTIVE: The objective of this study was to develop evidence-based recommendations on pregnancy management for persons with multiple sclerosis (MS). BACKGROUND: MS typically affects young women in their childbearing years. Increasing evidence is available to inform questions raised by MS patients and health professionals about pregnancy issues. METHODS: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and university databases (January 1975 through June 2021). The RAND/UCLA appropriateness method was developed to synthesise the scientific literature and expert opinions on healthcare topics; it was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS: A strong agreement was reached for all 104 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, locoregional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses and disease-modifying treatments. CONCLUSION: The 2022 recommendations of the French MS society should be helpful to harmonise counselling and treatment practice for pregnancy in persons with MS, allowing for better and individualised choices.

Improving the decision to switch from first- to second-line therapy in multiple sclerosis: A dynamic scoring system.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. OBJECTIVE: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. METHODS: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). RESULTS: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09-0.22) for the waiting group and 0.40 (95% CI 0.32-0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30-0.46) and 0.44 (95% CI 0.37-0.52), respectively. CONCLUSIONS: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.

Pregnancy and neuromyelitis optica spectrum disorders: 2022 recommendations from the French Multiple Sclerosis Society.

BACKGROUND: In 2020, the French Multiple Sclerosis (MS) Society (SFSEP) decided to develop a national evidence-based consensus on pregnancy in MS. As neuromyelitis optica spectrum disorders (NMOSD) shares a series of commonalities with MS, but also some significant differences, specific recommendations had to be developed. OBJECTIVES: To establish recommendations on pregnancy in women with NMOSD. METHODS: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and universities databases (January 1975 through June 2021). The RAND/UCLA appropriateness method, which was developed to synthesise the scientific literature and expert opinions on health care topics, was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A sub-group of nine NMOSD experts was dedicated to analysing available data on NMOSD. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. RESULTS: A strong agreement was reached for all 66 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, loco-regional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses, and disease-modifying treatments. CONCLUSION: Physicians and patients should be aware of the new and specific evidence-based recommendations of the French MS Society for pregnancy in women with NMOSD. They should help harmonise counselling and treatment practise, allowing for better individualised choices.

The Use of a Fixed 50:50 Mixture of Nitrous Oxide and Oxygen to Reduce Lumbar Puncture-Induced Pain in the Emergency Department: A Randomized Controlled Trial.

Lumbar puncture (LP) is stressful and often painful. We evaluated the efficacy of a fixed 50% nitrous oxide−oxygen mixture (50%N2O-O2) versus placebo to reduce immediate procedural pain and anxiety during LP performed in an emergency setting. We conducted a randomized controlled trial involving adults who needed a cerebrospinal fluid analysis in an emergency department. Patients were randomly assigned to inhale either 50%N2O-O2 or medical air. The primary endpoint, assessed using a numerical scale, was the maximum pain felt by the patient during the procedure and the maximum anxiety and satisfaction as secondary outcomes. Eighty-eight patients were randomized and analyzed (ITT). The maximal pain was 5.0 ± 2.9 for patients receiving air and 4.2 ± 3.0 for patients receiving 50%N2O-O2 (effect-size = −0.27 [−0.69; 0.14], p = 0.20). LP-induced anxiety was 4.7 ± 2.8 vs. 3.7 ± 3.7 (p = 0.13), and the proportion of patients with significant anxiety (score ≥ 4/10) was 72.7% vs. 50.0% (p = 0.03). Overall satisfaction was higher among patients receiving 50%N2O-O2 (7.4 ± 2.4 vs. 8.9 ± 1.6, p < 0.001). No serious adverse events were attributable to 50%N2O-O2 inhalation. Although inhalation of 50%N2O-O2 failed to reduce LP-induced pain in an emergency setting, it tended to reduce anxiety and significantly increased patient satisfaction.

Pharmacological treatments of neuropathic pain: real-life comparisons using propensity score matching.

ABSTRACT: Studies comparing different drug treatments for chronic neuropathic pain (NP) are very limited. We, therefore, examined 4 recommended treatments, namely, antidepressants (duloxetine, venlafaxine, and tricyclic antidepressants), antiepileptics (gabapentine and pregabalin), weak opioids, and strong opioids, among patients with NP evaluated before first visit in a tertiary pain treatment centre and 6 months later. Patients with both a clinical diagnosis of NP and a DN4 score ≥3/7 were selected from patients enrolled in the Quebec Pain Registry. Each participant was assigned an inverse weighting of the probability of receiving any NP treatment, taking into account their age, sex, baseline pain intensity, pain duration, pain catastrophizing tendency, education level, employment, and comedications at 6-month follow-up (M6). Patients were considered as improved if they presented at least a 30% reduction on average pain intensity at M6 compared with baseline. A total of 944 patients completed both baseline and M6 evaluations. Overall, 23.0% of patients were significantly improved for pain intensity at M6. There was no significant difference in proportions patients taking or not antidepressants, gabapentinoids, or weak opioids. Among patients taking strong opioids (N = 288), 13.9% (N = 40/288) were improved vs 27.0% (177/656) of those who were not on opioids (P < 0.004). Inverse probability of treatment weighting confirmed that the proportion of patients who improved was significantly lower among those taking strong opioids compared with those who did not (P < 0.001). In conclusion, long-term use of strong opioids is a treatment suited for a limited proportion of patients with chronic NP.

Estimation of sample size in randomized controlled trials in multiple sclerosis studying annualized relapse rates: A systematic review.

BACKGROUND: In multiple sclerosis (MS) studies, the most appropriate model for the distribution of the number of relapses was shown to be the negative binomial (NB) distribution. OBJECTIVE: To determine whether the sample-size estimation (SSE) and the analysis of annualized relapse rates (ARRs) in randomized controlled trials (RCTs) were aligned and compare the SSE between normal and NB distributions. METHODS: Systematic review of phase 3 and 4 RCTs for which the primary endpoint was ARR in relapsing remitting MS published since 2008 in pre-selected major medical journals. A PubMed search was performed on 30 November 2020. We checked whether the SSE and ARR analyses were congruent. We also performed standardized (fixed α/ß, number of arms and overdispersion) SSEs using data collected from the studies. RESULTS: Twenty articles (22 studies) were selected. NB distribution (or quasi-Poisson) was used for SSE in only 7/22 studies, whereas 21/22 used it for ARR analyses. SSE relying on NB regression necessitated a smaller sample size in 21/22 of our calculations. CONCLUSION: SSE was rarely performed using the most appropriate model. However, the use of an NB model is recommended to optimize the number of included patients and to be congruent with the final analysis.

CCR5 Blockade in Inflammatory PML and PML-IRIS Associated With Chronic Inflammatory Diseases' Treatments.

BACKGROUND AND OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) is a disabling neurologic disorder resulting from the infection of the CNS by JC polyomavirus in immunocompromised individuals. For the last 2 decades, increasing use of immunotherapies leads to iatrogenic PML. Iatrogenic PML is often associated with signs of inflammation at onset (inflammatory PML) and/or after treatment withdrawal immune reconstitution inflammatory syndrome (PML-IRIS). Although immune reconstitution is a key element for viral clearance, it may also be harmful and induce clinical worsening. A C-C chemokine receptor type 5 (CCR5) antagonist (maraviroc) has been proposed to prevent and/or limit the deleterious immune responses underlying PML-IRIS. However, the data to support its use remain scarce and disputed. METHODS: We conducted a multicenter retrospective cohort study at 8 university hospitals in France and Switzerland by collecting clinical, biological, and radiologic data of patients who developed inflammatory PML (iPML) or PML-IRIS related to immunosuppressive therapies used for chronic inflammatory diseases between 2010 and 2020. We added to this cohort, a meta-analysis of individual case reports of patients with iPML/PML-IRIS treated with maraviroc published up to 2021. RESULTS: Overall, 27 cases were identified in the cohort and 9 from the literature. Among them, 27 met the inclusion criteria: 16 treated with maraviroc and 11 with standard of care (including corticosteroids use). Most cases were related to MS (92.6%) and natalizumab (88%). Inflammatory features (iPML) were present at onset in 12 patients (44.4%), and most patients (92.6%) received corticosteroids within the course of PML. Aggravation due to PML-IRIS was not prevented by maraviroc compared with patients who received only corticosteroids (adjusted odds ratio: 0.408, 95% CI: 0.06-2.63). Similarly, maraviroc did not influence time to clinical worsening due to PML-IRIS (adjusted hazard ratio = 0.529, 95% CI: 0.14-2.0) or disability at the last follow-up (adjusted odds ratio: 2, 95% CI: 0.23-17.3). DISCUSSION: The use of CCR5 blockade did not help to keep deleterious immune reconstitution in check even when associated with corticosteroids. Despite maraviroc's reassuring safety profile, this study does not support its use in iPML/PML-IRIS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence showing that adding maraviroc to the management of iatrogenic iPML/PML-IRIS does not improve the outcome.

Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica.

INTRODUCTION: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. CASE SERIES: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. DISCUSSION: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.

Untreated patients with multiple sclerosis: A study of French expert centers.

BACKGROUND AND PURPOSE: Disease-modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. METHODS: We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. RESULTS: Of the 21,189 patients with MS (age 47.1 ± 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 ± 2.4), 6,631 (31.3%; 95% confidence interval [CI] 30.7-31.9) were not receiving any DMT. Although patients with a relapsing-remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing-remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio [OR] 0.52 [95% CI 0.44-0.61]) and lower EDSS score (OR 0.78 [95% CI 0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. CONCLUSION: A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.

Characteristics of pain in patients with pituitary adenomas: A cross-sectional study.

BACKGROUND: This study determines the prevalence and particularities of headache and pain with neuropathic characteristics (NC) in a large French group of patients with pituitary adenoma (PA). METHODS: Analysis of validated self-administered questionnaires, radiological characteristics and treatment strategies of PA was performed. RESULTS: Of the 221 sent questionnaires, 146 could be used for statistical analysis, 50% of which were completed by women. Among responders, 58.9% had pain: 30.1% migraine, 15.7% pain with NC and 13.1% other types of pain. Migraine was more common in patients with PA than in the general population (30.1% vs. 21.3%, p = .010) and attacks received appropriate treatment for less than 20% of these patients. Furthermore, the prevalence of chronic migraine was much higher than in the general population (6.8% vs. 2.2%, p = .003). Neuropathic pain was also more frequent in PA patients than in the general population (15.8% vs. 6.9%, p < .001). Neuropathic pain was most often located in the extremities and was frequently described as an 'electric shock', 'numbness', or 'pins-and-needles'. Multivariate analyses linked migraine to younger age, anxiety, pain with NC, and a visible tumour on MRI, regardless of its invasiveness or secretory nature. CONCLUSIONS: Migraine headaches and neuropathic pain are more frequent and disabling in PA patients than in the general population. Both types of pain are comorbid in PA patients and are poorly treated. Migraine is associated with the presence of a tumour. Thus, biological mechanisms of this relationship need to be characterized to design optimal treatments for these individuals. SIGNIFICANCE: Migraine headaches and neuropathic pain are more common in PA patients than in the general population and are generally poorly treated. A systematic screening for migraine should be done by physicians in daily practice to provide adequate therapeutics.