Exercise-Induced Change in Plasma IL-12p70 Is Linked to Migraine Prevention and Anxiolytic Effects in Treatment-Naïve Women: A Randomized Controlled Trial.

OBJECTIVE: To conduct a randomized controlled trial to evaluate the effect of a 12-week aerobic exercise program for migraine prevention, plasma cytokines concentrations (TNF-α, interleukin [IL]-1ß, IL-6, IL-8, IL-10, and IL-12p70), and anxiety in women with migraine. METHODS: Women with episodic migraine (ICHD-II), aged between 20 and 50 years, who had never taken any prophylactic medication, and were physically inactive in the past 12 months were recruited from the university's hospital and a tertiary headache clinic between March 2012 and March 2015. Migraine attacks were recorded in headache diaries, cytokines were quantified by flow cytometry, and anxiety was assessed by the 7-item General Anxiety Disorder (GAD-7) scale. Blood sampling and psychometric interviews were undertaken on headache-free days. RESULTS: Twenty participants ([mean ± SD] age 33.8 ± 10.5; BMI 26 ± 5.2) were randomly assigned and received intervention ("trained": n = 10) or entered on a waitlist ("inactive": n = 10). There were no differences between groups regarding patients' characteristics and baseline data. Days with migraine (p = 0.001), IL-12p70 levels (p = 0.036), and GAD-7 score (p = 0.034) were significantly reduced in the trained group after the intervention period, but there were no significant changes in these variables in the inactive group. There was no change in the levels of the other cytokines in either group. There were positive correlations between a reduction in IL-12p70 level and a reduction in the number of days with migraine (R2 = 0.19, p = 0.045), and GAD-7 score (R2 = 0.53, p < 0.001). CONCLUSION: The clinical and psychological therapeutic effects of aerobic exercise in treatment-naïve women with migraine may involve the downregulation of IL-12p70.

Randomised clinical trial comparing melatonin 3†mg, amitriptyline 25†mg and placebo for migraine prevention.

INTRODUCTION: Melatonin has been studied in headache disorders. Amitriptyline is efficacious for migraine prevention, but its unfavourable side effect profile limits its use. METHODS: A randomised, double-blind, placebo-controlled study was carried out. Men and women, aged 18-65 years, with migraine with or without aura, experiencing 2-8 attacks per month, were enrolled. After a 4-week baseline phase, 196 participants were randomised to placebo, amitriptyline 25 mg or melatonin 3 mg, and 178 took a study medication and were followed for 3 months (12 weeks). The primary outcome was the number of migraine headache days per month at baseline versus last month. Secondary end points were responder rate, migraine intensity, duration and analgesic use. Tolerability was also compared between groups. RESULTS: Mean headache frequency reduction was 2.7 migraine headache days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo. Melatonin significantly reduced headache frequency compared with placebo (p=0.009), but not to amitriptyline (p=0.19). Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency. Melatonin was better tolerated than amitriptyline. Weight loss was found in the melatonin group, a slight weight gain in placebo and significantly for amitriptyline users. CONCLUSIONS: Melatonin 3 mg is better than placebo for migraine prevention, more tolerable than amitriptyline and as effective as amitriptyline 25 mg.

Anandamide Is Related to Clinical and Cardiorespiratory Benefits of Aerobic Exercise Training in Migraine Patients: A Randomized Controlled Clinical Trial.

Introduction: Since endocannabinoids have been implicated in migraine pathophysiology, we conducted a randomized, controlled clinical trial to test the effects of a 12-week aerobic exercise intervention on plasma anandamide (AEA) and its relation with clinical, psychological, and cardiorespiratory outcomes. Materials and Methods: Episodic migraine patients taking no preventive drugs and nonheadache individuals were recruited from Hospital São Paulo and a tertiary headache clinic between March 2012 and March 2015. Participants were randomly assigned to receive aerobic exercise or enter the waitlist. Primary outcome was changes in plasma AEA; secondary outcome was number of days with migraine/month; and other clinical variables, mood scores, and cardiorespiratory fitness were chosen as tertiary outcomes. Measurements were taken on headache-free days. Data were analyzed by generalized linear models. Discussion: Fifty participants concluded the study (mean±SD age=36.2±10.9, and BMI=26.5±4.5). The plasma AEA reduced in migraine exercise (p<0.05) and control exercise groups (p<0.01). The number of days with migraine (p<0.01), migraine attacks (p<0.05), and abortive medication used (p<0.05) reduced in the migraine exercise group, whereas cardiorespiratory fitness increased in migraine exercise and control exercise groups (both p<0.05). Anxiety, depression, anger, and fatigue scores improved in the migraine exercise group (p<0.05 for all). Significant correlations between reduction in abortive medication used and cardiorespiratory fitness (r=-0.81 p<0.001), and reduced AEA (r=0.68 p<0.05) were found. Conclusions: This study suggests that peripheral AEA metabolism may be partly linked to the clinical and cardiorespiratory benefits of regular aerobic exercise in migraine patients. Trials registration: #NCT01972607.

Glossopharyngeal neuralgia with syncope as a sign of neck cancer recurrence.

Glossopharyngeal neuralgia with syncope as a sign of neck cancer is a very rare condition. A review of the literature revealed only 29 cases formerly reported. We present the first Brazilian case of such association. A 68-year-old man presented with paroxysmal excruciating pain over the right side of the neck, sometimes followed by syncope. Given the suspicion of recurrent tumor from a previously treated neck malignancy, a computed tomography scan was performed and a right parapharyngeal tumor was shown. Pain and syncope were successfully controlled with carbamazepine and the patient underwent palliative radiotherapy.

Unbalanced plasma TNF-α and IL-12/IL-10 profile in women with migraine is associated with psychological and physiological outcomes.

Increased plasma pro-inflammatory and decreased anti-inflammatory cytokines have been implicated in physiological and behavioural aspects of mood- and pain-related disorders, including migraine. In this case-control study, we assessed mood scores, cardiorespiratory fitness (VO2Peak), and plasma concentrations of TNF-α, IL-1ß, IL-6, IL-8, IL-10, and IL-12p70 interictally in women with episodic migraine with/without aura (ICHD-II), taking no preventive medicine, and in healthy women recruited from São Paulo Hospital and local community, respectively. Thirty-seven participants (mean±SD age=34±10 and BMI=26.5±4.9) were assessed. Groups (Control, n=17; Migraine, n=20) showed no differences in age, BMI, and VO2Peak. Migraine patients showed higher tension (p=0.019) and anxiety scores (p=0.046), TNF-α (p<0.01), and IL-12p70 (p=0.01), while IL-6 (p<0.01), IL-8 (p<0.01), and IL-10 (p<0.01) were decreased compared to control group. Multiple linear regression models showed that migraine was positively associated with TNF-α and IL-12p70, and negatively associated with IL-6, IL-8, and IL-10. Anxiety scores were positively associated with IL-12p70, and VO2Peak was negatively associated with TNF-α. In conclusion, an exaggeratedly skewed cytokine profile, in particular the TNF-α and 12p70/IL-10 balance may be related to migraine pathomechanisms, and its psychiatric comorbidities and functional capacity. Additional studies are needed to confirm these results.

Inherited manganism: the "cock-walk" gait and typical neuroimaging features.

Manganese (Mn) toxicity causes an extrapyramidal, parkinsonian-type movement disorder with characteristic magnetic resonance images of Mn accumulation in the basal ganglia. This letter highlights the neurological manifestations and neuroimaging features of inherited manganism (IMn), an unusual and treatable inborn error of Mn homeostasis. Early-onset dystonia with "cock-walk" gait and hyperintense signal in basal ganglia, associated to polycythemia, chronic liver disease and hypermanganesemia, promptly suggest IMn, and a genetic evaluation should be performed.

Factors associated with acute medication overuse in chronic migraine patients.

OBJECTIVE: To evaluate the prevalence of psychiatric disorders in patients diagnosed with chronic migraine with and without acute medication overuse. METHODS: Seventy-two volunteers were recruited from a Family Health Program of the Paraisópolis community in São Paulo (SP), Brazil. These patients were submitted to a detailed headache questionnaire. All participants were submitted to physical and neurological examinations. The following variables were analyzed: age, gender, education level, body mass index, type of overused medication, headache characteristics, and caffeine consumption, lifetime anxiety and mood disorders. RESULTS: Out of 72 patients, 50 (69%) had chronic migraine with medication overuse, and 22 (31%) had chronic migraine without medication overuse. Factors such as age, gender, education level, body mass index, type of overused medication, headache characteristics, and caffeine consumption were not significantly different between the two studied groups. Lifetime anxiety and mood disorders were more common in patients with acute medication overuse (p=0.003 and p=0.045, respectively). CONCLUSION: This study has shown a significant association among chronic migraine and medication overuse with lifetime mood and anxiety disorders in patients of the studied population. No association was found for other researched psychiatric disorders.

Fatores associados ao uso excessivo de medicação sintomática em pacientes com enxaqueca crônica / Factors associated with acute medication overuse in chronic migraine patients

OBJETIVO: Avaliar a prevalência de transtornos psiquiátricos em pacientes com diagnóstico de enxaqueca crônica com e sem uso excessivo de medicação sintomática. MÉTODOS: Setenta e dois voluntários foram recrutados a partir de um Programa de Saúde da Família da comunidade de Paraisópolis, na cidade de São Paulo (SP). Esses pacientes foram submetidos a exames clínico e neurológico. As seguintes variáveis foram analisadas: idade, gênero, nível educacional, índice de massa corporal, tipo de uso excessivo de medicação, características da cefaleia, consumo de cafeína, presença de ansiedade e distúrbios de humor. RESULTADOS: Dos 72 pacientes, 50 (69%) tinham cefaleia crônica, com uso exagerado de medicação, e 22 (31%) tinham cefaleia crônica, sem uso excessivo de medicação. Os fatores idade, gênero, nível educacional, índice de massa corporal, tipo de uso excessivo de medicação, características da cefaleia e consumo de cafeína não mostraram diferença significante entre os grupos estudados. Os diagnósticos de ansiedade e de distúrbios de humor ao longo da vida foram mais comuns nos pacientes com uso excessivo de medicação (p=0,003 e p=0,045, respectivamente). CONCLUSÃO: Este estudo mostrou uma associação significativa entre cefaleia crônica e uso excessivo de medicação nos pacientes avaliados, quanto ao diagnóstico de transtornos de ansiedade e de humor ao longo da vida. Não foi encontrada nenhuma associação com outros distúrbios psiquiátricos pesquisados.

OBJECTIVE: To evaluate the prevalence of psychiatric disorders in patients diagnosed with chronic migraine with and without acute medication overuse. METHODS: Seventy-two volunteers were recruited from a Family Health Program of the Paraisópolis community in São Paulo (SP), Brazil. These patients were submitted to a detailed headache questionnaire. All participants were submitted to physical and neurological examinations. The following variables were analyzed: age, gender, education level, body mass index, type of overused medication, headache characteristics, and caffeine consumption, lifetime anxiety and mood disorders. RESULTS: Out of 72 patients, 50 (69%) had chronic migraine with medication overuse, and 22 (31%) had chronic migraine without medication overuse. Factors such as age, gender, education level, body mass index, type of overused medication, headache characteristics, and caffeine consumption were not significantly different between the two studied groups. Lifetime anxiety and mood disorders were more common in patients with acute medication overuse (p=0.003 and p=0.045, respectively). CONCLUSION: This study has shown a significant association among chronic migraine and medication overuse with lifetime mood and anxiety disorders in patients of the studied population. No association was found for other researched psychiatric disorders.

Glossopharyngeal neuralgia with syncope as a sign of neck cancer recurrence

Glossopharyngeal neuralgia with syncope as a sign of neck cancer is a very rare condition. A review of the literature revealed only 29 cases formerly reported. We present the first Brazilian case of such association. A 68-year-old man presented with paroxysmal excruciating pain over the right side of the neck, sometimes followed by syncope. Given the suspicion of recurrent tumor from a previously treated neck malignancy, a computed tomography scan was performed and a right parapharyngeal tumor was shown. Pain and syncope were successfully controlled with carbamazepine and the patient underwent palliative radiotherapy.

Neuralgia glossofaríngea com síncope como um sinal de câncer do pescoço é uma condição muito rara. Uma revisão da literatura revelou apenas 29 casos relatados anteriormente. Apresentamos o primeiro caso brasileiro de tal associação. Um homem de 68 anos se apresentou com dores paroxísticas insuportáveis no lado direito do pescoço, algumas vezes seguidas de síncope. Dada a suspeita de recidiva tumoral derivada de uma malignidade cervical tratada previamente, realizou-se um exame de tomografia computadorizada que evidenciou um tumor parafaríngeo direito. As dores e as síncopes foram controladas satisfatoriamente com carbamazepina e o paciente foi submetido à radioterapia paliativa.