International Headache Society global practice recommendations for the acute pharmacological treatment of migraine.

BACKGROUND: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications. METHODS: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group. RESULTS: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained. CONCLUSION: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited.

High rates of (treated) hypothyroidism among chronic migraine patients consulting a specialized headache clinic: are we missing something?

BACKGROUND: Roughly three percent of episodic migraine patients evolve into the most burdensome chronic form of this condition every year. While some of the determinants behind this transformation are well established, others are still ill defined. Hypothyroidism is a prevalent endocrinological disorder that can both produce a secondary headache or aggravate a pre-existing primary headache disorder such as migraine. OBJECTIVE: We aimed to re-assess the association between hypothyroidism and chronic migraine controlling for factors such as hormone replacement treatment status and bodyweight. METHODS: We retrospectively analyzed the medical records of episodic and chronic migraine patients who consecutively consulted our headache clinic in order to determine the prevalence of adequately treated hypothyroidism in each group. Only patients receiving a stable dose regimen were included. The body mass index and other possibly confounding covariates were also collected. RESULTS: Data from 111 migraine patients was included for analysis. Most (88.6%) of chronic migraine sufferers were overusing acute medication. Treated hypothyroidism was significantly more prevalent in chronic migraine patients (29.55%) compared to episodic migraine patients (8.96%). This association was independent of the patients' body mass index or other variables. CONCLUSION: Alterations of neuronal metabolism, deficient calcitonin release, or focal inflammation causing local hormonal deactivation might explain why hypothyroidism, in spite of levothyroxine replacement therapy, is associated with migraine chronification. Further studies evaluating these factors are warranted.

Psychological, clinical, and therapeutic predictors of the outcome of detoxification in a large clinical population of medication-overuse headache: A six-month follow-up of the COMOESTAS Project.

AIM: To identify factors that may be predictors of the outcome of a detoxification treatment in medication-overuse headache. METHODS: Consecutive patients entering a detoxification program in six centres in Europe and Latin America were evaluated and followed up for 6 months. We evaluated anxious and depressive symptomatology (though patients with severe psychiatric comorbidity were excluded), quality of life, headache-related disability, headache characteristics, and prophylaxis upon discharge. RESULTS: Of the 492 patients who completed the six-month follow up, 407 ceased overuse following the detoxification (non overusers), another 23 ceased overuse following detoxification but relapsed during the follow-up. In the 407 non-overusers, headache acquired an episodic pattern in 287 subjects (responders). At the multivariate analyses, lower depression scores (odds ratio = 0.891; p = 0.001) predicted ceasing overuse. The primary headache diagnosis - migraine with respect to tension-type headache (odds ratio = 0.224; p = 0.001) or migraine plus tension-type headache (odds ratio = 0.467; p = 0.002) - and the preventive treatment with flunarizine (compared to no such treatment) (odds ratio = 0.891; p = 0.001) predicted being a responder. A longer duration of chronic headache (odds ratio = 1.053; p = 0.032) predicted relapse into overuse. Quality of life and disability were not associated with any of the outcomes. CONCLUSIONS: Though exploratory in nature, these findings point to specific factors that are associated with a positive outcome of medication-overuse headache management, while identifying others that may be associated with a negative outcome. Evaluation of the presence/absence of these factors may help to optimize the management of this challenging groups of chronic headache sufferers.

Economic benefits of treating medication-overuse headache - results from the multicenter COMOESTAS project.

BACKGROUND: Medication-overuse headache is a costly disease for individuals and society. OBJECTIVE: To estimate the impact of medication-overuse headache treatment on direct and indirect headache-related health care costs. METHODS: This prospective longitudinal study was part of the COMOESTAS project (COntinuous MOnitoring of Medication Overuse Headache in Europe and Latin America: development and STAndardization of an Alert and decision support System). Patients with medication-overuse headache were included from four European and two Latin American headache centers. Costs of acute medication, costs of health care services, and measurements of productivity were calculated at baseline and at 6-month follow-up Treatment consisted of overused drug withdrawal with optional preventive medication. RESULTS: A total of 475 patients (71%) completed treatment and were followed up for 6 months. Direct health care costs were on average reduced significantly by 52% ( p < 0.001) for the total study population. Significant reductions were seen in both number of consumed tablets (-71%, p < 0.001) and number of visits to physicians (-43%, p < 0.001). Fifty percent of patients reduced their number of consumed tablets ≥ 80%. Headache-related productivity loss, calculated either as absence from work or ≥ 50% reduction of productivity during the workday, were reduced by 21% and 34%, respectively ( p < 0.001). CONCLUSION: Standardized treatment of medication-overuse headache in six countries significantly reduced direct health care costs and increased productivity. This emphasizes the importance of increasing awareness of the value of treating medication-overuse headache. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (no. NCT02435056).

Clinical Subtypes of Medication Overuse Headache - Findings From a Large Cohort.

BACKGROUND: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population. METHOD: This descriptive cross-sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self-administered questionnaires for measuring disability, anxiety, and depression. RESULTS: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T-MOH) with respect to subjects overusing simple analgesic (A-MOH). Duration of headache before chronification was longer in T-MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E-MOH, 17.8 ± 11.7 years) with respect to the A-MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T-MOH with respect multiple drug classes (M-MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E-MOH group (33.6 ± 41.6), while T-MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M-MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ2  = 10.953, P = .027 and χ2  = 25.725, P < .001, respectively). CONCLUSION: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache.

Changes in anxiety and depression symptoms associated to the outcome of MOH: A post-hoc analysis of the Comoestas Project.

Aims To evaluate the impact of treatment success on depression and anxiety symptoms in medication-overuse headache (MOH) and whether depression and anxiety can be predictors of treatment outcome. Methods All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion over a six-month period. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. Results A total of 663 MOH patients were evaluated, and 492 completed the entire protocol. Of these, 287 ceased overuse and reverted to an episodic pattern (responders) and 23 relapsed into overuse. At the final evaluation, the number of patients with depressive symptoms was reduced by 63.2% among responders ( p < 0.001) and did not change in relapsers ( p = 0.13). Anxious symptomatology was reduced by 43.1% in responders ( ps < 0.001) and did not change in relapsers ( p = 0.69). At the multivariate analysis, intake of a prophylactic drug and absence of symptoms of depression at six months emerged as prognostic factors for being a responder (OR 2.406; p = 0.002 and OR 1.989; p = 0.019 respectively), while lack of antidepressant drugs and presence of symptoms of depression at six months were prognostic factors for relapse into overuse (OR 3.745; p = 0.004 and OR 3.439; p = 0.031 respectively). Conclusions Symptomatology referred to affective state and anxiety can be significantly reduced by the treatment of MOH. Baseline levels of depression and anxiety do not generally predict the outcome at six months. Their persistence may represent a trait of patients with a negative outcome, rather than the consequence of a treatment failure.

Clinical and Demographical Characteristics of Patients with Medication Overuse Headache in Argentina and Chile: Analysis of the Latin American Section of COMOESTAS Project.

BACKGROUND: Data on the characteristics of Medication Overuse Headache (MOH) in Latin American (LA) are scarce. Here we report the demographic and clinical features of the MOH patients from Argentina and Chile enrolled in the multinational COMOESTAS project in the period 2008-2010. METHODS: The LA population was formed by 240 MOH subjects, 110 from Chile and 130 from Argentina, consecutively attending the local headache centres. In each centre, specifically trained neurologist interviewed and confirmed the diagnosis according to the ICHD-II criteria. A detailed history was collected on an electronic patient record form. RESULTS: The mean patient age was 38.6 years, with a female/male ratio of 8:2. The mean time since onset of the primary headache was 21 years, whereas duration of MOH was 3.9 years. The primary headache was migraine without aura in 77.5 % and migraine with aura in 18.8 %. Forty two % of the patients self-reported emotional stress associated with the chronification of headache; 43.8 % reported insomnia. The most overused medications were acute drug combinations containing ergotamine (70 %), NSAIDs (33.8 %) and triptans (5.4 %). CONCLUSION: Though little described, MOH is present also in LA, where it affects mostly women, in the most active decades of life. Some differences emerge as regards the demographic and clinical characteristics of MOH in this population as compared to Europe or Northern America. What seems more worrying about MOH in Argentina and Chile is that most patients overuse ergotamine, a drug that may cause serious adverse events when used chronically. These findings once more underscore the importance of properly diagnose and treat MOH.

Medication overuse headache in Europe and Latin America: general demographic and clinical characteristics, referral pathways and national distribution of painkillers in a descriptive, multinational, multicenter study.

BACKGROUND: Medication overuse headache (MOH) is a very disabling and costly disorder due to indirect costs, medication and healthcare utilization. The aim of the study was to describe general demographic and clinical characteristics of MOH, along with the national referral pathways and national painkillers distribution in several European and Latin American (LA) Countries. METHODS: This descriptive cross-sectional observational study included 669 patients with MOH referred to headache-centers in Europe and LA as a part of the COMOESTAS project. Information about acute medication and healthcare utilization were collected by extensive questionnaires, supplemented with structured patient interviews. RESULTS: Triptans were overused by 31 % European patients and by 6 % in LA (p < 0.001), whereas ergotamines were overused by 4 % in Europe and 72 % in LA (p < 0.001). Simple analgesics were overused by 54 % in Europe and by 33 % in LA (p < 0.001), while combination-analgesics were more equally overused (24 % in Europe and 29 % in LA). More European patients (57 %) compared with LA patients (27 %) visited general practitioners (p < 0.001), and 83 % of European patients compared to 38 % in LA consulted headache specialists (p < 0.001). A total of 20 % in Europe and 30 % in LA visited emergency rooms (p = 0.007). CONCLUSION: There are marked variations between LA and Europe in healthcare pathways and in acute medication overuse regarding patients with MOH. This should be considered when planning prevention campaigns against MOH.

Migraine in older adults.

Migraine is an evolving, and sometimes lifelong disorder. The prevalence of episodic migraine peaks among individuals aged in their late 30s, implying a tendency for the disorder to remit with increasing age thereafter, whereas chronic migraine is more likely to persist into later life. Diagnosis and treatment of migraine in older adults, defined as individuals aged 60 years or older, is rendered more complex by increasing probabilities of atypical clinical features and comorbidities, with patients' comorbidities sometimes limiting their therapeutic options. However, the changing clinical presentation of migraine over an individual's lifespan is not well characterised. The neurobiological basis of remission in older adults remains unclear, although vascular, neuronal, and hormonal changes are likely to be involved. Long-term longitudinal studies of individuals with migraine would be particularly informative, with the potential not only to suggest new research directions, but also to lead to the identification of novel therapeutic agents. Although several novel migraine medications are becoming available, their effectiveness, tolerability, and safety often remain uncertain in older adults, who have commonly been excluded from the evaluation of these agents in randomised controlled trials, or who constitute only a small proportion of study populations. There is a need to recognise these limitations in the available evidence, and the specific, and often unmet, clinical needs of older adults with migraine, not least because older adults constitute an increasing proportion of populations worldwide.

[Migraine preventive treatment: monoclonal antibodies against calcitonine gene related peptide]. / Tratamiento preventivo en migraña: anticuerpos monoclonales contra la vía del péptido relacionado con el gen de la calcitonina.

Migraine is a very prevalent disorder that is estimated to affect about 10-15% of adult subjects. According to the World Health Organization migraine is one of the first causes of disability. Traditional preventive treatments discovered by serendipity include Beta blockers, antinconvulsants drugs, calcium channel blockers, tricyclic antidepressants and onabotulinum A and offer about 50% efficacy after controlled placebo trials and real life use. Because of lack of adherence and adverse events, there is a loss of beneficial sustain on these treatments. Recently, the efficacy and safety of monoclonal antibodies (MA) that act on the peptide pathway related to the calcitonin gene (CGRP) has been evaluated in migraine, being the first specific tailored treatment on one of the multiple targets on migraine. This family of drugs: erenumab, galcanezumab, fremanezumab, eptinezumab, finished Fase III, extensions trials and many of them are in the market approved since 2018.Since 2019 are available in Argentina. We will describe the rationale for the prescription of this family of new drugs for migraine.

La migraña es un trastorno muy prevalente que afecta a alrededor del 15% de los sujetos adultos. Es clasificada por la Organización Mundial de la Saludentre los primeros puestos como causa de discapacidad. Los tratamientos preventivos habituales hasta ahora derivan de otras indicaciones y por serendipia se utilizan en prevención de migraña: betabloqueantes, drogas antiepilépticas, antidepresivos tricíclicos, bloqueantes de canales de calcio, toxina botulínica. Todas ellas han mostrado eficacia similar al 50% en reducir el número de episodios migrañosos pese a efectos secundarios indeseados. Durante los últimos años, se ha evaluado la eficacia y seguridad de los anticuerpos monoclonales (AM) que actúan sobre la vía del péptido relacionado con el gen de la calcitonina (CGRP) en migraña. Dicho péptido es relevante en la activación del dolor en territorio meníngeoy es mediado por terminales nerviosas trigeminales una vez activado el proceso migrañoso. Su dosaje en crisis migrañosas ha sido elevado en diversos estudios y su neutralización/bloqueo, redunda en alivio del dolor. Los anticuerpos monoclonales erenumab, galcanezumab, fremanezumab, eptinezumab aprobados en el mercado EE.UU./Europa desde 2018 y tras varios trabajos de Fase III y abiertos de extensión, mostraron clara seguridad yeficacia y están presentes en nuestro medio desde mediados de 2019. Desarrollamos la racionalidad e indicaciones de uso de los mismos.

Postcraniectomy pain: comparison between 2 incisions for the retrosigmoid approach. Prospective randomized study. / Dolor poscraniectomía: comparación entre 2 incisiones para el abordaje retrosigmoideo. Estudio prospectivo aleatorizado.

BACKGROUND: Suboccipital lateral approach is a common practice in neurosurgery to expose the region of the cerebellopontine angle. Postcraniectomy headache (PCH) is one of the most frequent complications that diminish the quality of life of patients. OBJECTIVE: To compare postcraniectomy pain in patients operated on for vestibular neurinomas by a suboccipital lateral approach by 2 different incisions. MATERIAL AND METHODS: Prospective randomized research study. Follow-up of patients operated for vestibular neurinomas between July 2017 and May 2019 (n=40) by the same surgeon. One group received the classical linear incision (n=20) and another group the alternative incision in an inverted "U" (modified Dandy) (n=20). Pain intensity was evaluated by numerical scale. A minimum follow-up of 3 months was carried out. The impact on quality of life was measured by the SF-36 questionnaire short version both before and after surgery. RESULTS: The average age was 46.1 years. The overall PCH index was 27.5% (n=11) of the patients. The incidence of pain in the group that received the classical incision (A) was 20% (n=4) and in group B was 35% (n=7). CONCLUSIONS: We found a higher rate of post-craniectomy headache in patients who underwent a "modified Dandy" incision. These are preliminary data of an undergoing study and we hope to obtain more representative information in the future. We recommend interdisciplinary follow up for the integral treatment of PCH.

Tratamiento preventivo en migraña: anticuerpos monoclonales contra la vía del péptido relacionado con el gen de la calcitonina / Migraine preventive treatment: monoclonal antibodies against calcitonine gene related peptide

Resumen La migraña es un trastorno muy prevalente que afecta a alrededor del 15% de los sujetos adultos. Es clasificada por la Organización Mundial de la Saludentre los primeros puestos como causa de discapacidad. Los tratamientos preventivos habituales hasta ahora derivan de otras indicaciones y por serendipia se utilizan en prevención de migraña: betabloqueantes, drogas antiepilépticas, antidepresivos tricíclicos, bloquean tes de canales de calcio, toxina botulínica. Todas ellas han mostrado eficacia similar al 50% en reducir el número de episodios migrañosos pese a efectos secundarios indeseados. Durante los últimos años, se ha evaluado la eficacia y seguridad de los anticuerpos monoclonales (AM) que actúan sobre la vía del péptido relacionado con el gen de la calcitonina (CGRP) en migraña. Dicho péptido es relevante en la activación del dolor en territorio meníngeoy es mediado por terminales nerviosas trigeminales una vez activado el proceso migrañoso. Su dosaje en crisis migrañosas ha sido elevado en diversos estudios y su neutralización/bloqueo, redunda en alivio del dolor. Los anticuerpos monoclonales erenumab, galcanezumab, fremanezumab, eptinezumab aprobados en el mercado EE.UU./Europa desde 2018 y tras varios trabajos de Fase III y abiertos de extensión, mostraron clara seguridad yeficacia y están presentes en nuestro medio desde mediados de 2019. Desarrollamos la racionalidad e indicaciones de uso de los mismos.

Abstract Migraine is a very prevalent disorder that is estimated to affect about 10-15% of adult subjects. Ac cording to the World Health Organization migraine is one of the first causes of disability. Traditional preventive treatments discovered by serendipity include Beta blockers, antinconvulsants drugs, calcium channel blockers, tricyclic antidepressants and onabotulinum A and offer about 50% efficacy after controlled placebo trials and real life use. Because of lack of adherence and adverse events, there is a loss of beneficial sustain on these treat ments. Recently, the efficacy and safety of monoclonal antibodies (MA) that act on the peptide pathway related to the calcitonin gene (CGRP) has been evaluated in migraine, being the first specific tailored treatment on one of the multiple targets on migraine. This family of drugs: erenumab, galcanezumab, fremanezumab, eptinezumab, finished Fase III, extensions trials and many of them are in the market approved since 2018.Since 2019 are available in Argentina. We will describe the rationale for the prescription of this family of new drugs for migraine.

Mitoxantrone as rescue therapy in worsening relapsing-remitting MS patients receiving IFN-beta.

We assessed the action of mitoxantrone (MX) when given as rescue therapy in patients with relapsing-remitting (RR) multiple sclerosis (MS), whose disease activity worsens despite IFN-beta treatment. Ten very active RR MS patients received MX 12 mg/m2 monthly, for 3 months, and then returned to the original treatment with IFN-beta. Following treatment with MX, 70% of patients were able to return to IFN-beta treatment, stabilising EDSS and relapse rate during a follow-up period of 15-18 additional months. In contrast, in 30% of the patients who were taken off MX and returned to IFN-beta treatment the EDSS score deteriorated and the number of exacerbations increased significantly. The latter patients were switched again to MX treatment at 3-month intervals, stabilising EDSS and relapse rate during 15-18 additional months. Clinical findings correlated with the number of Gd-enhancing lesions disclosed in MRI scans. Immunological data were consistent with the clinical and MRI benefits observed. We conclude that brief courses of MX may provide a safe treatment alternative for RR MS patients who experience rapid and severe worsening of their disease despite IFN-beta treatment.

Lipomatosis of the trigeminal nerve causing trigeminal neuralgia: case report and literature review.

UNLABELLED: Cerebellopontine angle lipomas are rare and attempts at surgical excision are associated with significant morbidity. Lipomatosis of nerve, the fatty infiltration of nerves, is a distinct entity. We present a case of intractible trigeminal neuralgia caused by lipomatosis of the trigeminal nerve. CLINICAL CASE: A 25-year-old male presented with severe right-sided trigeminal neuralgia. Imaging showed a lesion involving the trigeminal nerve with signal characteristics of fat. At surgery the lesion was found to be a fatty infiltration of the nerve itself. Surgery was therefore limited to arachnoid adhesiolysis. The patient remains symptom-free and neurologically intact to date. Correctly identifying these lesions as lipomatosis of nerve rather than lipoma of the cerebellopontine angle make it clear that even partial surgical excision will inevitably result in neurological deficit and should not be attempted. However, in the case of intractable trigeminal neuralgia we demonstrate that surgery can still play a role.