Long-term safety of OnabotulinumtoxinA treatment in chronic migraine patients: a five-year retrospective study.

Background: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting. Methods: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability. Results: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues. Conclusion: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

Migraine treatment consensus document of the Spanish Society of Neurology (SEN), Spanish Society of Family and Community Medicine (SEMFYC), Society of Primary Care Medicine (SEMERGEN) and Spanish Association of Migraine and Headache (AEMICE) on migraine treatment. / Documento de consenso de la Sociedad Española de Neurología (SEN), Sociedad Española de Medicina de Familia y Comunitaria (SEMFYC), Sociedad de Medicina de Atención Primaria (SEMERGEN) y Asociación Española de Migraña y Cefalea (AEMICE) sobre el tratamiento de la migraña.

Migraine is a disease with a high prevalence and incidence, in addition to being highly disabling, causing a great impact on the patient's quality of life at a personal, family and work level, but also social, given its high expense due to its direct (care) and indirect (presenteeism and work absenteeism) costs. The multiple and recent developments in its pathophysiological knowledge and in its therapy require updating and, therefore, in this article the Spanish scientific societies most involved in its study and treatment (SEN, SEMFYC and SEMERGEN), together with the Association Spanish Association for Patients with Migraine and other Headaches (AEMICE), we have developed these updated care recommendations. We reviewed the treatment of migraine attacks, which consisted mainly of the use of NSAIDs and triptans, to which ditans and gepants have been added. We also discuss preventive treatment consisting of oral preventive drugs, botulinum toxin, and treatments that block the action of calcitonin-related peptide (CGRP). Finally, we emphasize that pharmacological treatments must be complementary to carrying out general measures consisting of identifying and managing/deletion the precipitating factors of the attacks and the chronicizing factors, controlling the comorbidities of migraine and eliminating analgesic overuse.

Is erenumab an efficient alternative for the prevention of episodic and chronic migraine in Spain? Results of a cost-effectiveness analysis.

BACKGROUND: The reimbursement of erenumab in Spain and other European countries is currently restricted because of the cost of this novel therapy to patients with migraine who have experienced previous failures to traditional preventive treatments. However, this reimbursement policy should be preferably based on cost-effectiveness studies, among other criteria. This study performed a cost-effectiveness analysis of erenumab versus topiramate for the prophylactic treatment of episodic migraine (EM) and versus placebo for chronic migraine (CM). METHODS: A Markov model with a 10-year time horizon, from the perspective of the Spanish National Healthcare System, was constructed based on data from responder and non-responder patients. A responder was defined as having a minimum 50% reduction in the number of monthly migraine days (MMD). A hypothetical cohort of patients with EM with one or more prior preventive treatment failures and patients with CM with more than two treatment failures was considered. The effectiveness score was measured as an incremental cost per quality-adjusted life year (QALY) gained and cost per migraine day (MD) avoided. Data from clinical outcomes and patient characteristics were obtained from erenumab clinical trials (NCT02066415, STRIVE, ARISE, LIBERTY and HER-MES). Deterministic and probabilistic sensitivity analyses were performed to validate the robustness of the model. RESULTS: After a 10-year follow-up, the estimated QALYs were 5.88 and 6.11 for patients with EM treated with topiramate and erenumab, respectively. Erenumab showed an incremental cost per patient of €4,420 vs topiramate. For CM patients, erenumab resulted in 0.756 QALYs gained vs placebo; and an incremental cost of €1,814. Patients treated with erenumab achieved reductions in MD for both EM and CM (172 and 568 MDs, respectively). The incremental cost per QALY gained with erenumab was below the Spanish threshold of €30,000/QALY for both health and societal perspectives (EM €19,122/QALY and CM €2,398/QALY). CONCLUSIONS: Erenumab is cost-effective versus topiramate as a preventive treatment for EM and versus placebo for patients with CM from the perspective of the Spanish National Health System.

Eptinezumab for the preventive treatment of episodic and chronic migraine: a narrative review.

Eptinezumab, a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), was recently approved in Europe for the prophylactic treatment of migraine in adults who have at least four migraine days a month. Eptinezumab is administered by intravenous infusion every 12 weeks. During recent months, a considerable amount of evidence from eptinezumab trials has been published. The aim of this review is to describe the existing evidence on the tolerability, safety and efficacy of eptinezumab in patients with migraine. Data from randomized (PROMISE-1, PROMISE-2, RELIEF and DELIVER) and open-label (PREVAIL) phase 3 clinical trials have demonstrated the favorable effect of eptinezumab in migraine symptoms from first day of treatment. These studies showed that eptinezumab results in an overall reduction in mean monthly migraine days (MMDs), increases in the ≥50% and ≥ 75% migraine responder rates (MRRs) and improvements in patient-reported outcome measures in both patients with episodic migraine (EM) and with chronic migraine (CM), including patients who failed previous preventive treatments. The RELIEF trial also showed that eptinezumab, within 2 h of administration, reduced headache pain, migraine-associated symptoms and acute medication use when administered during a migraine attack. Eptinezumab benefits manifested as early as day 1 after dosing and with the subsequent doses lasted up to at least 2 years. Treatment-emergent adverse events reported by ≥2% of patients included upper respiratory tract infection and fatigue. Current evidence demonstrates that eptinezumab has a potent, fast-acting, sustained migraine preventive effect in patients with EM and CM. Eptinezumab has also shown to be well tolerated, supporting its use in the treatment of patients with migraine and inclusion in the current migraine therapeutic options.

Persistence, use of resources and costs in patients under migraine preventive treatment: the PERSEC study.

BACKGROUND: Migraine represents a serious burden for national health systems. However, preventive treatment is not optimally applied to reduce the severity and frequency of headache attacks and the related expenses. Our aim was to assess the persistence to traditional migraine prophylaxis available in Spain and its relationship with the healthcare resource use (HRU) and costs. METHODS: Retrospective observational study with retrospective cohort design of individuals with migraine treated with oral preventive medication for the first time from 01/01/2016 to 30/06/2018. One-year follow-up information was retrieved from the Big-Pac™ database. According to their one-year persistence to oral prophylaxis, two study groups were created and describe regarding HRU and healthcare direct and indirect costs using 95% confidence intervals (CI). The analysis of covariance (ANCOVA) was performed as a sensitivity analysis. Patients were considered persistent if they continued on preventive treatment until the end of the study or switched medications within 60 days or less since the last prescription. Non-persistent were those who permanently discontinued or re-initiated a treatment after 60 days. RESULTS: Seven thousand eight hundred sixty-six patients started preventive treatment (mean age (SD) 48.2 (14.8) and 80.4% women), of whom 2,545 (32.4%) were persistent for 6 months and 2,390 (30.4%) for 12 months. Most used first-line preventive treatments were antidepressants (3,642; 46.3%) followed by antiepileptics (1,738; 22.1%) and beta-blockers (1,399; 17.8%). The acute treatments prescribed concomitantly with preventives were NSAIDs (4,530; 57.6%), followed by triptans (2,217; 28.2%). First-time preventive treatment prescribers were mostly primary care physicians (6,044; 76.8%) followed by neurologists (1,221; 15.5%). Non-persistent patients required a higher number of primary care visits (mean difference (95%CI): 3.0 (2.6;3.4)) and days of sick leave (2.7 (0.8;4.5)) than the persistent ones. The mean annual expenditure was €622 (415; 829) higher in patients who not persisted on migraine prophylactic treatment. CONCLUSIONS: In this study, we observed a high discontinuation rate for migraine prophylaxis which is related to an increase in HRU and costs for non-persistent patients. These results suggest that the treatment adherence implies not only a clinical benefit but also a reduction in HRU and costs.

Treatment of Primary Nummular Headache: A Series of 183 Patients from the NUMITOR Study.

Nummular headache (NH) is a primary headache characterized by superficial coin-shaped pain. NUMITOR (NCT05475769) is an observational study evaluating the responder rate of preventive drugs in NH patients. The treatment response was assessed between weeks 8 and 12 compared with the baseline. Patients were included between February 2002 and October 2022. Demographic and clinical variables were assessed; treatment response was estimated by 50%, 30%, and 75% responder rates and treatment discontinuation due to inadequate tolerability. A total of 183 out of 282 patients fulfilled eligibility criteria and completed the study. Patients were aged 49.5 (standard deviation (SD): 16.8) years, and 60.7% were female. NH phenotype was a parietal circular pain of four centimeters' diameter, moderate intensity, and oppressive quality. At baseline, patients had 25 (interquartile range) pain days per month. Preventive treatment was used by 114 (62.3%) patients. The highest 50% and 75% responder rates corresponded to onabotulinumtoxinA (62.5%, 47.5%), followed by gabapentin (43.7%, 35.2%). Oral preventive drugs were not tolerated by 12.9-25%. The present study provides class IV evidence of the effectiveness of oral preventive drugs and onabotulinumtoxinA in the treatment of primary NH. OnabotulinumtoxinA was the most effective and best-tolerated drug, positioning it as first-line treatment of NH.

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention.

BACKGROUND: Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. METHODS: Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. RESULTS: We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A-BoNT/A-had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%). CONCLUSIONS: In real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.

Cost of fremanezumab, erenumab, galcanezumab and onabotulinumtoxinA associated adverse events, for migraine prophylaxis in Spain.

Objective: To compare the cost of adverse events (AEs) associated with preventive treatment of migraine with fremanezumab, versus erenumab, galcanezumab, and onabotulinumtoxinA.Methods: A probabilistic modeling analysis was performed, using second-order Monte Carlo simulations, with 1,000 simulations, in patients with at least 4 days of migraine per month, from the perspective of the National Health System and a time horizon of 12 weeks. The frequency of AEs described in the clinical trials was analyzed with 12 weeks of treatment. Unit costs (€) of management of AEs were obtained from public health prices, expert panels, and published Spanish studies.Results: Fremanezumab would generate average savings of -€469 (95% CI -€303; -€674) versus erenumab, -€268 (95% CI -€171; -€391) versus galcanezumab, -€1,100 (95% CI -€704; -€1,608) or -€1,295 (95% CI -€835; -€1,893) versus onabotulinumtoxinA using real-life or clinical trial data, respectively.Conclusions: The different safety profile of treatment with fremanezumab, compared to erenumab, galcanezumab, and onabotulinumtoxinA, would generate savings in health-care resources in all the scenarios considered.

Cutaneous Allodynia in Migraine: A Narrative Review.

OBJECTIVE: In the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine. BACKGROUND: CA is regarded as the perception of pain in response to non-noxious skin stimulation. The number of research studies relating to CA and migraine has increased strikingly over the last few decades. Therefore, the clinician treating migraine patients must recognize this common symptom and have up-to-date knowledge of its importance from the pathophysiological, diagnostic, prognostic and therapeutic point of view. METHODS: We performed a comprehensive narrative review to analyze existing literature regarding CA in migraine, with a special focus on epidemiology, pathophysiology, assessment methods, risk for chronification, diagnosis and management. PubMed and the Cochrane databases were used for the literature search. RESULTS: The prevalence of CA in patients with migraine is approximately 60%. The mechanisms underlying CA in migraine are not completely clarified but include a sensitization phenomenon at different levels of the trigemino-talamo-cortical nociceptive pathway and dysfunction of brainstem and cortical areas that modulate thalamocortical inputs. The gold standard for the assessment of CA is quantitative sensory testing (QST), but the validated Allodynia 12-item questionnaire is preferred in clinical setting. The presence of CA is associated with an increased risk of migraine chronification and has therapeutic implications. CONCLUSIONS: CA is a marker of central sensitization in patients with migraine that has been associated with an increased risk of chronification and may influence therapeutic decisions.

Interictal amylin levels in chronic migraine patients: A case-control study.

BACKGROUND: Recently, amylin and its receptors were found in different structures involved in migraine pathophysiology. Here, we evaluate interictal concentrations of amylin and calcitonin gene-related peptide in peripheral blood as biomarkers for chronic migraine. METHODS: We prospectively recruited patients with episodic migraine, chronic migraine and healthy controls. Interictal amylin and calcitonin gene-related peptide levels were assessed in blood samples using enzyme linked immunosorbent assay. RESULTS: We assessed plasma samples from 58 patients with episodic migraine (mean age 37.71 ± 10.47, 87.9% female), 191 with chronic migraine (mean age 46.03 ± 11.93, 95% female), and on 68 healthy controls (mean age 43.58 ± 11.08 years, 86% female). Body mass index was 25.94 ± 4.53 kg/m2 for migraine patients and 25.13 ± 4.92 kg/m2 for healthy controls (p = 0.0683). Interictal plasma amylin levels were higher in chronic migraine patients (47.1 pg/mL) than in the episodic migraine patients (28.84 pg/mL, p < 0.0001) and healthy controls (24.74 pg/mL, p < 0.0001). Plasma calcitonin gene-related peptide levels were increased (20.01 pg/mL) in chronic migraine patients when compared to healthy controls (11.37 pg/mL, p = 0.0016), but not to episodic migraine patients (18.89 pg/mL, p = 0.4369). Applying a cut-off concentration of 39.68 pg/mL plasma amylin, the sensitivity to differentiate chronic migraine from healthy controls was 57.6% and the specificity was 88.2%. Variables such as age, analgesic overuse, depression, allodynia, use of preventive medication or a history of aura did not influence the plasma concentrations of amylin or calcitonin gene-related peptide. CONCLUSION: Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a diagnostic biomarker for chronic migraine.

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study.

BACKGROUND: Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS: This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. RESULTS: The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. CONCLUSIONS: Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.

Excess abdominal fat is associated with cutaneous allodynia in individuals with migraine: a prospective cohort study.

OBJECTIVE: To investigate the specific relationship between cutaneous allodynia (CA) and the percentages of body fat (BF) and abdominal fat in migraineurs. Additionally, we compared serum levels of inflammatory biomarkers in patients with and without CA. BACKGROUND: Excess abdominal fat might facilitate progressive changes in nociceptive thresholds causing central sensitization, clinically reflected as CA, which could drive migraine progression. METHODS: This prospective cohort study included 80 patients with migraine (mean age 39 years, 81.2% female) and 39 non-migraine controls. We analysed each participant's height, body weight, and body mass index (BMI). The amount and distribution of BF was also assessed by air displacement plethysmography (ADP) and ViScan, respectively. We analysed serum levels of markers of inflammation, during interictal periods. RESULTS: We studied 52 patients with episodic migraine (EM) and 28 with chronic migraine (CM). Of the 80 patients, 53 (53.8%) had CA. Migraineurs with CA had a higher proportion of abdominal fat values than patients without CA (p = 0.04). The independent risk factors for CA were the use of migraine prophylaxis (OR 3.26, 95% CI [1.14 to 9.32]; p = 0.03), proportion of abdominal fat (OR 1.13, 95% CI [1.01 to 1.27]; p = 0.04), and presence of sleep disorders (OR 1.13, 95% CI [00.01 to 1.27]; p = 0.04). The concordance correlation coefficient between the ADP and BMI measurements was 0.51 (0.3681 to 0.6247). CA was not correlated with the mean plasma levels of inflammatory biomarkers. CONCLUSIONS: There is a relation between excess abdominal fat and CA. Abdominal obesity might contribute to the development of central sensitization in migraineurs, leading to migraine chronification.

Facial solitary morphea profunda presenting with painful trigeminal neuropathy: A case report.

BACKGROUND: Localized facial scleroderma usually presents as frontal linear morphea or progressive hemifacial atrophy. Only isolated cases of trigeminal painful neuropathy have been described. CASE REPORT: A 43-year-old woman developed an oval lesion on the right cheek. After 1 year, she noticed constant "pulling" pain and episodes of lancinating pain, both spontaneous and triggered by chewing and cold drinks. She was diagnosed with solitary morphea profunda and CT scan, ultrasonography, cranial MRI and biopsy were completed. Methylprednisolone (1 gr/day for 3 days) was prescribed. For pain, gabapentin, oxcarbazepine, amitryptiline, pregabalin and eslicarbacepine were all ineffective. A capsaicin patch was placed with prolonged benefit. Later on, the pain slightly worsened; occipital blockade was effective and methotrexate was recommended. CONCLUSION: This is the first case of solitary morphea profunda associated with painful trigeminal neuropathy. Treatment should include immunosuppressants and treatment of neuropathic pain, in which local therapies seem particularly beneficial.

Headache and Ophthalmoparesis: Case Report of an "Atypical" Incomplete Miller-Fisher Syndrome.

OBJECTIVE: To expand the differential diagnosis of headache and ophthalmoparesis by describing a case report in which anti-GQ1b was demonstrated to be the cause. BACKGROUND: Anti-GQ1b antibody syndrome refers to a clinical spectrum of conditions that share common mechanisms and overlapping manifestations, including the Miller-Fisher syndrome, pharyngeal-cervical-brachial weakness, and Bickerstaff brainstem encephalitis. Rare atypical cases presenting as acute ophthalmoparesis (AO) without ataxia or areflexia have been described. Headache is a rare condition in these disorders. METHODS: A 49-year-old woman with no history of headaches began experiencing an acute severe bilateral throbbing headache associated with nausea and photophobia. Five days later, she developed constant binocular horizontal diplopia. RESULTS: Bilateral paresis of both sixth nerves was noted. Her ocular fundi, tendon reflexes, and other findings of the physical exam were normal. In addition, both a brain MRI performed with gadolinium and a lumbar puncture yielded normal results. Serum anti-GQ1b IgG was found to be positive. Her symptoms resolved completely following treatment with immunoglobulins (0.4 g/kg/day for 5 days). CONCLUSIONS: This is the first reported case of AO related to anti-GQ1b antibodies presenting with headache as its initial symptom. The presence of anti-GQ1b antibodies should be determined in patients with headache and AO of unknown origin. Immunoglobulins could hasten the resolution of symptoms in these patients.

Stylohyoid Complex (Eagle) Syndrome Starting in a 9-Year-Old Boy.

Background There are only four previous pediatric reports of the glossopharyngeal neuralgic form of the stylohyoid complex syndrome. Stylohyoid complex has merely been described as cases of glossopharyngeal neuralgia in children. Case Report A 12-year-old boy came to our hospital because of recurrent episodes of severe cranial pain (9/10) lasting for 5 to 15 minutes. Pain affected the right tonsillar fossa, ear, and mastoid region. Since the start at the age of 9 years, the frequency of painful episodes has progressively increased: when admitted to our clinics 3 years later, the child was having up to five episodes daily in spite of analgesic, antiepileptic, and antidepressant drugs; he had abandoned school and leisure. Between episodes, neurological examination detected only discomfort to pressure on the right tonsillar fossa. Three-dimensional computed tomography images of the skull base showed an elongated right styloid process and bilateral calcification of the stylohyoid ligament. After surgical excision of the right styloid process and of part of the stylohyoid ligament, the glossopharyngeal painful episodes ceased. The patient remains asymptomatic seven years later. Conclusion In spite of its rarity in childhood, this debilitating but treatable syndrome should be kept in mind for the differential diagnosis of recurrent cranial pain in the pediatric population.

Epicardial Adipose Tissue in the General Middle-aged Population and Its Association With Metabolic Syndrome.

INTRODUCTION AND OBJECTIVES: There is currently increasing interest in epicardial adipose tissue (EAT) as a marker of cardiovascular disease. Our purpose was to describe EAT, measured by transthoracic echocardiography, and to assess its association with metabolic syndrome (MS) in the RIVANA population-based study. METHODS: Physical examination was performed in 880 participants aged 45 to 74 years (492 of them with MS according to the harmonized definition). Fasting glucose, high-density lipoprotein cholesterol, triglyceride, and C-reactive protein concentrations were determined in a blood sample. In all participants, EAT thickness was measured with transthoracic echocardiography at end-systole. RESULTS: Among participants without MS, the prevalence of EAT ≥ 5mm significantly increased with age (OR > 65 years vs 45-54 years=8.22; 95%CI, 3.90-17.35; P for trend<.001). Increasing EAT quintiles were significantly associated with MS (OR fifth quintile vs first quintile=3.26; 95%CI, 1.59-6.71; P for trend=.001). Considering the different MS criteria, increasing quintiles of EAT were independently associated with low high-density lipoprotein cholesterol (OR fifth quintile vs first quintile=2.65; 95%CI, 1.16-6.05; P for trend=.028), high triglycerides (OR fifth quintile vs first quintile=2.22; 95%CI, 1.26-3.90; P for trend=.003), and elevated waist circumference (OR fifth quintile vs first quintile=6.85; 95%CI, 2.91-16.11; P for trend<.001). CONCLUSIONS: In a subsample of the general population, EAT measured by echocardiography increased significantly and independently with age. Increased EAT thickness was independently associated with MS and with low high-density lipoprotein cholesterol, high triglycerides, and elevated waist circumference as individual criteria.

Monitoring the Effect of Immunotherapy in Autoimmune Limbic Encephalitis Using 18F-FDG PET.

A 70-year-old woman with a history of autoimmune hepatitis and renal cell carcinoma presented with subacute cognitive impairment. A brain MRI revealed mild leukoaraiosis, whereas brain F-FDG PET/CT showed diffuse cerebral hypometabolism that resembled some of the patterns described in limbic encephalitis and neurodegenerative diseases. With the suspicion of autoimmune encephalitis, the patient received immunotherapy with dramatic improvement of cognitive function and metabolic normalization at the 2-month follow-up on brain F-FDG PET/CT. Our results demonstrate that brain F-FDG PET/CT might be a useful tool in the assessment of patients with autoimmune encephalitis.

[What is the optimal dose for the prophylactic treatment of chronic migraine patients?]. / Realmente es beneficioso usar las dosis de OnabotulinumtoxinA del estudio PREEMPT?

INTRODUCTION: OnabotulinumtoxinA (OnabotA) is indicated for headache prophylaxis in patients with chronic migraine. However, there is some controversy about what is the minimum effective dose for treating chronic migraine patients. AIM: To determine the optimal dose of OnabotA for the prophylactic treatment of patients with chronic migraine. DEVELOPMENT: We performed a literature review of the randomized, double blind, placebo-controlled studies that have evaluated the safety and efficacy of OnabotA as headache prophylactic treatment in migraine patients. In the studies conducted before the PREEMPT clinical programme, a variety of dose ranges and infiltration paradigms were used. Initial phase II studies of OnabotA in chronic daily headache showed that those patients treated with 150 U had significant mean reductions from baseline in headache frequency compared with placebo, and this benefit was not observed for patients treated with 75 U. The experience from previous studies allowed to define an injection paradigm and dose range (155-195 U) that was used in the PREEMPT clinical trials. PREEMPT studies demonstrate that OnabotA is a safe an effective prophylactic treatment for chronic migraine. CONCLUSIONS: Available evidence to date supports that the optimal dose for the treatment of chronic migraine patients is the use of at least 150 U of OnabotA, that should be administered according to the PREEMPT injection paradigm.

TITLE: Realmente es beneficioso usar las dosis de OnabotulinumtoxinA del estudio PREEMPT?Introduccion. La OnabotulinumtoxinA (OnabotA) esta indicada para el tratamiento preventivo de los pacientes con diagnostico de migraña cronica. Existe cierta controversia acerca de cual es la dosis minima eficaz de OnabotA. Objetivo. Determinar cual es la dosis mas adecuada de OnabotA para el tratamiento de la migraña cronica. Desarrollo. Se revisan los estudios controlados frente a placebo, que han evaluado la eficacia y seguridad de OnabotA para el tratamiento de la migraña, prestando especial atencion a las dosis de toxina utilizadas. En los diferentes ensayos clinicos llevados a cabo antes del año 2010 se utilizaron distintos protocolos de infiltracion. La experiencia obtenida de los estudios previos permitio definir un protocolo de infiltracion que se utilizo en el programa PREEMPT, y que demostro que el tratamiento con OnabotA es seguro y eficaz en pacientes con migraña cronica. La dosis elegida en los ensayos PREEMPT 1 y 2 fue de 155-195 U, al observarse en los estudios en fase II que la dosis de 75 U no era eficaz y que la utilizacion de 150-200 U aumentaba la eficacia sin incrementar los efectos adversos. Ademas de la dosis, el paradigma de inyeccion PREEMPT tambien establece de manera detallada los puntos de inyeccion y la metodologia de infiltracion. Conclusiones. La evidencia cientifica disponible hasta la fecha sustenta que la dosis mas adecuada para el tratamiento de la migraña cronica es la utilizacion de al menos 150 U de OnabotA, y que la infiltracion debe realizarse con la metodologia definida en el paradigma de inyeccion PREEMPT.