Investigation of the relationship between thrombophilic disorders and brain white matter lesions in migraine with aura.

BACKGROUND: Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. OBJECTIVE: Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. METHODS: The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. RESULTS: Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. CONCLUSION: The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.

ANTECEDENTES: La migraña se asocia con una serie de comorbilidades genéticas o adquiridas. Los estudios realizados en los últimos años destacan que la frecuencia de trombofilia es elevada en la migraña, especialmente en la migraña con aura (MA). De manera similar, la presencia de lesiones de la sustancia blanca (LSB) en las imágenes por resonancia magnética (RM) del cerebro se ha asociado con la migraña hace muchos años. OBJETIVO: Con base en la información de que se suelen observar tanto LSB como variantes de la trombofilia en MA, nuestro objetivo fue investigar si existe una relación entre la trombofilia genética y la presencia de LSB en estos pacientes. MéTODOS: Se investigaron los niveles de proteína S y de proteína C, actividades de antitrombina III, resistencia a la proteína C activada (PCA), anticuerpos antifosfolípidos inmunoglobulina G/inmunoglobulina M (IgG/IgM) y anticuerpos anticardiolipina IgG/IgM en 66 pacientes con MA entre 18 y 49 años que no presentaban factores de riesgo cardiovascular. Se determinaron la presencia de LSB y el grado de Fazekas a partir de imágenes por RM del cerebro en la secuencia ponderada en T2 y recuperación de la inversión atenuada de fluido (fluid-attenuated inversion recovery, FLAIR, en inglés) obtenidas de los pacientes. Se compararon las tasas de LSB en pacientes con y sin trombofilia. RESULTADOS: Se detectó trombofilia en el 34,8% de los pacientes y LSB en el 27,3%. Las LSB estuvieron presentes en el 23,3% de los pacientes sin trombofilia, en el 34,8% de los que tenían trombofilia, y en el 50% de los que tenían múltiples trastornos trombofílicos. La resistencia a la PCA fue significativamente más común en aquellos pacientes con LSB. CONCLUSIóN: Los resultados del presente estudio mostraron que la trombofilia puede ser un mecanismo que debe investigarse en la etiología del aumento de LSB en MA.

Migraine aura discrimination using machine learning: an fMRI study during ictal and interictal periods.

Functional magnetic resonance imaging (fMRI) studies on migraine with aura are challenging due to the rarity of patients with triggered cases. This study optimized methodologies to explore differences in ictal and interictal spatiotemporal activation patterns based on visual stimuli using fMRI in two patients with unique aura triggers. Both patients underwent separate fMRI sessions during the ictal and interictal periods. The Gaussian Process Classifier (GPC) was used to differentiate these periods by employing a machine learning temporal embedding approach and spatiotemporal activation patterns based on visual stimuli. When restricted to visual and occipital regions, GPC had an improved performance, with accuracy rates for patients A and B of roughly 86-90% and 77-81%, respectively (p < 0.01). The algorithm effectively differentiated visual stimulation and rest periods and identified times when aura symptoms manifested, as evident from the varying predicted probabilities in the GPC models. These findings contribute to our understanding of the role of visual processing and brain activity patterns in migraine with aura and the significance of temporal embedding techniques in examining aura phenomena. This finding has implications for diagnostic tools and therapeutic techniques, especially for patients suffering from aura symptoms.

Actualización sobre la comorbilidad migraña-depresión / Update on migraine-depression comorbidity

Introducción: La migraña y el trastorno depresivo son patologías altamente prevalentes e incapacitantes, las cuales presentan relaciones bidireccionales de comorbilidad. En la literatura se han descrito factores de riesgo y mecanismos fisiopatológicos comunes para ambas enfermedades, así como asociaciones entre estas y su presentación clínica. Métodos: El presente texto es una revisión narrativa de la literatura. La búsqueda del material bibliográfico se hizo mediante distintas bases de datos especializadas en el área de la salud. Resultados: Algunos factores de riesgo están asociados con ambas patologías, y ambas comparten factores patogénicos, incluidos cambios funcionales, estructurales, genéticos, epigenéticos y hormonales, entre otros. Varios de los tratamientos preventivos que han demostrado eficacia en el tratamiento de la migraña son medicamentos o medidas con efecto antidepresivo. Discusión: Si se consideran las asociaciones y los factores comunes descritos en la literatura, se hace evidente que en el enfoque de pacientes diagnosticados con alguna de estas patologías es necesario tener en cuenta una posible comorbilidad entre migraña y depresión. Conclusión: Es importante promover el tamizaje de estas dos condiciones en pacientes diagnosticados con alguna de ellas, pues esto puede tener implicaciones terapéuticas e impacto en la calidad de vida.

Introduction: Migraine and depressive disorder are highly prevalent and disabling pathologies, which present bidirectional relationships of comorbidity. Common risk factors and pathophysiological mechanisms for both diseases have been described in the literature, as well as associations between them and their clinical presentation. Methods: This text is a narrative literature review. The bibliographical material was found through different databases specialized in health sciences. Results: Some risk factors are associated with both pathologies, and both share pathogenic factors, including functional, structural, genetic, epigenetic, hormonal changes, among others. Several of the preventive treatments that have shown efficacy in the treatment of migraine are medications or measures with an antidepressant effect. Discussion: Considering the associations and common factors described in the literature, it becomes evident that in the approach to patients diagnosed with any of these pathologies, it may be beneficial to consider a possible migraine-depression comorbidity. Conclusion: It is important to promote the screening of these two patients diagnosed with some, since it can have therapeutic implications and impact on quality of life.

Renumab como tratamiento profiláctico de migraña crónica / Renumab as a prophylactic treatment for chronic migraine

ÁREA DESCRIPTIVA DEL MEDICAMENTO Y DEL PROBLEMA DE SALUD: La migraña es una condición médica común e incapacitante caracterizada por episodios recurrentes de cefalea moderada o grave que dura horas o días y que usualmente se acompaña de otros síntomas associados. Dentro de ellas, la migraña crónica (MC) se define como aquella que aparece durante 15 días o más al mes durante más de tres meses, y que, al menos durante 8 días al mes, presenta características de cefalea migrañosa. Por su parte, la migraña episódica (ME) (no recogida en la clasificación de la International Headache Society (IHS) se define como la cefalea que aparece entre y 14 días al mes. La relación entre MC y ME es compleja, ya que ésta evoluciona a la primera a una tasa de, % por año y a veces la MC remite a ME (2 % de transición a los 2 años). La división de 15 episodios por mes como frontera entre ambos tipos de migraña es arbitraria, pero estas definiciones clínicas identifican grupos con características diferenciales. Principales manifestaciones clínicas Una crisis típica de migraña se caracteriza por: dolor de cabeza palpitante e incapacitante, que habitualmente se acompaña de fotofobia, fonofobia y náuseas, generalmente unilateral, aunque puede ser bilateral. Aproximadamente un 15-33% de los pacientes presentan un aura antes de la crisis, que consiste en un conjunto de síntomas neurológicos como alteraciones visuales, hemisensoriales o anomalías del lenguaje, con una duración entre 5 y 60 minutos. El aura más común es la visual que consiste en una luz intermitente o ampliación del punto ciego, un borde brillante o dentado o líneas en la visión periférica. En los casos menos comunes también puede sentirse entumecimiento, hormigueo en cara y brazo, alteraciones del pensamiento o del habla. Habitualmente la migraña se manifiesta en la hora siguiente al aura, pero en algunos casos el aura no progresa a cefalea. En ocasiones pueden aparecer síntomas de aura atípica, como debilidad muscular; diplopía, síntomas visuales que afectan a un sólo ojo, pérdida de equilibrio o disminución del nivel de conciencia, y en estos casos hay que considerar la realización de pruebas adicionales o la derivación. El inicio de la migraña se produce generalmente en la adolescencia temprana y puede seguir cursos diferentes, remitiendo tras unos pocos años, recurriendo en ciclos durante años o cronificándose en unos pocos pacientes. METOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas Pubmed: Erenumab y migraña de igual forma se realiza la búsqueda realizada en la base de datos clinicaltrials.org usando los términos "erenumab" y "migraña" aparecieron 7 ensayos clínicos; 4 fase II y 4 fase III; en ellos se incluyen los citados anteriormente, además de otro en curso en países diferentes de EEUU y la Unión Europea y ensayos que incluyen el uso en pacientes con angina estable y en combinación con sumatriptán. También se realizó búsqueda manual en otras bases de datos bibliográficas (Cochrane, NIH, TRIP DATABASE), en buscadores genéricos de internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, metaanálisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnología sanitaria, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. CONCLUSIONES: Erenumab ha sido aprobado para el tratamiento profiláctico de la migraña en pacientes con 4 o más días de migraña mensuales. Los ensayos que condujeron a la aprobación se diseñaron comparados con placebo, frente al cual el fármaco mostró eficacia estadísticamente significativa tanto en MC como en ME en las distintas variables consideradas: reducción del número de días mensuales de migraña, porcentaje de pacientes con reducciones de más del 50% de días de migraña mensuales, disminución del consumo de medicamentos específicos contra la migraña y mejora en la escalas de calidad de vida relacionada con la salud específicas de migraña. No hay ensayos directos entre erenumab y los fármacos de referencia que se usan actualmente (principalmente topiramato o toxina botulínica) pero las comparaciones indirectas publicadas no mostraron diferencias entre erenumab 70 mg o 140 mg frente a estos tratamientos. Únicamente la dosis de 140 mg mostró diferencias frente a topiramato en ME en la reducción del número de días de migraña al mes (pero no en tasa de respuesta del 50%) (DM 0,99 días, IC 95% -1,89 a -0,02) mientras que topiramato se mostró más eficaz que erenumab 70 mg en estas mismas condiciones (comparación indirecta ajustada). En MC no hubo diferencias con OBT-A. La relevancia clínica del beneficio encontrado en ME comparando erenumab 140 mg/mes frente a topiramato es muy discreta (reducción de 0,99 días de migraña al mes). Excepto en uno de los ensayos clínicos en el que se estudió erenumab en pacientes con fallo a 2-4 tratamientos previos, en el resto de los ensayos fue criterio de exclusión el fallo a más de 3 o a más de 2 tratamientos previos. Se consideró que erenumab podría abordar una necesidad insatisfecha identificada por grupos de pacientes de medicamentos seguros y efectivos para prevenir las migrañas crónicas en pacientes que han fracasado con dos o tres medicamentos profilácticos para la migraña. Un análisis de subgrupos preespecificado de esta población de pacientes del Estudio 295 (N = 667; 12 semanas de duración) demostró que erenumab redujo la cantidad de días mensuales con migraña en comparación con el placebo en 2,7 días (intervalo de confianza [IC] del 95 %, - 4,2 a ­1,2, P < 0,001) para la dosis de 70 mg y a los 4,3 días (IC del 95 %, ­5,8 a ­2,8, P < 0,001) con la dosis de 140 mg. El estudio excluyó a los pacientes que no habían experimentado ninguna respuesta terapéutica a cuatro o más medicamentos profilácticos previos para la migraña y, por lo tanto, no se pudo determinar la eficacia clínica de erenumab en estos pacientes. Erenumab es un fármaco bien tolerado en general, con eventos adversos leves y tolerables (nasofaringitis, infección respiratoria superior, dolor en el punto de administración, etc.) no demasiado diferente de los del placebo. Con respecto a otros fármacos usados como preventivos en la migraña (OBT-A, topiramato, amitriptilina, propanolol). Entre un 4,2% y un 8% de pacientes tratados con erenumab han presentado anticuerpos contra el fármaco (69 casos en la fase de investigación clínica), aunque únicamente en 2 fueron neutralizantes. Se carece de datos para conocer la seguridad de erenumab en poblaciones especiales (ancianos, embarazadas, niños, madres lactantes). Erenumab, por su administración única mensual que puede llevar a cabo el propio paciente, puede presentar ventajas de adherencia y resultar más cómodo para los pacientes frente a las alternativas orales que deben administrarse diariamente o frente a OBT-A que requiere de la administración mediante recursos especializados.

Evaluation of the relationship between migraine and psoriasis: a case-control study.

BACKGROUND: Although several recent studies have attempted to describe the association between psoriasis and migraine, there is little data in this regard. OBJECTIVE: To explore the relationship between migraine and psoriasis. METHODS: A total of 312 patients with psoriasis and 312 age- and gender-matched controls without psoriasis were recruited in this case-control study. Based on the diagnosis of migraine, they were divided into 4 subgroups: psoriasis with (PM+) and without (PM-) migraine, and control with (CM+) and without migraine (CM-). The subgroups were compared regarding the migraine and psoriasis characteristics. RESULTS: The mean (SD) age of patients and controls (139 males, in each group) was 43.2 (13.2) years. Psoriasis patients were significantly more likely to have migraine (OR = 2.789). Migraine with aura was significantly higher in the PM + group than in the CM + group (p = 0.007). The mean PASI score (p = 0.001), frequency of moderate and severe psoriasis (p = 0.048), and frequency of patients with PsA (p < 0.001) were significantly higher in PM + compared to PM-. The risk of migraine substantially increased with increasing psoriasis severity (OR = 2.062, OR = 3.248, and OR = 4.586 for mild, moderate, and severe, respectively), and with the presence of PsA (OR = 2.438 and OR = 12.930 for patients without and with PsA, respectively). STUDY LIMITATIONS: Observational nature, not including all confounding factors, not addressing a cause-and-effect relationship. CONCLUSIONS: In comparison with the non-psoriatic control group, psoriasis patients are predisposed to a significantly higher risk of migraine, particularly migraine with aura, psoriasis patients with more severe disease and those with PsA have a markedly higher risk of having migraine, and the migraine headache index is significantly higher in psoriasis patients.

Frecuencia de migraña y discapacidad generada en estudiantes de medicina humana de una universidad privada en Lima, Perú / Frequency of migraine and disability generated in medical students at a private university in Lima Peru

Objetivo : Estimar la frecuencia de migraña, y discapacidad generada en estudiantes de medicina de una universidad privada de Lima Metropolitana. Métodos : Estudio transversal en una muestra no probabilística por conveniencia, mediante la aplicación online del autocuestionario ALCOI-95, para evaluar la presencia de migraña, seguido por el cuestionario MIDAS para medir la discapacidad en los positivos al primer cuestionario. El rendimiento académico fue evaluado mediante el promedio ponderado de sus calificaciones. Resultados : Cuarenticinco (21,6%) de 208 estudiantes experimentaron migraña (12,5% con aura y 9,1% sin aura), 14 (33,3%) de los cuales mostraron discapacidad severa y 12 (28,6%) moderada. Los portadores de migraña con aura tuvieron una media menor del promedio ponderado acumulado de sus calificaciones, comparado con aquellos con migraña sin aura. Los factores independientemente asociados a la migraña fueron tener un miembro de la familia nuclear con migraña y problemas para mantener el sueño. Conclusión : Dos de cada 10 estudiantes presentaron migraña y 1/3 de los afectados experimentó discapacidad severa.

SUMMARY Objective: To estimate the frequency of migraine, associated factors and disability generated (including its relationship with academic performance) in medical students at a private university in Metropolitan Lima. Methods: Cross-sectional study in a non-probabilistic convenience sample using the online application of the ALCOI-95 self-questionnaire, to assess the presence of migraine, followed by the MIDAS questionnaire to measure disability in those positive to the first questionnaire. . Results: Fourty-five (21.6%) of 208 students experienced migraine (12.5% with aura and 9.1% without aura), 14 (33.3%) of whom showed severe, and 12 (28.6%) moderate disability. Migraine with aura carriers had a lower mean than the cumulative weighted average of their academic scores. Independent factors associated with migraine were to have a nuclear family member with migraine, and sleep-maintenance problems. Conclusion: Two out of 10 students had migraine, and one third of them had severe disability.

Migraine with aura and stroke - the role of warning signs in the context of secondary headaches: case report / Enxaqueca com aura e acidente vascular cerebral ­ o papel dos sinais de alerta no contexto das cefaleias secundárias: relato de caso

Introduction: Headache is a very common complaint in doctors' offices, with primary causes being the majority in relation to secondary ones. Despite this, the identification of secondary headaches is very relevant in clinical practice, since these can be a life-threatening condition, functionality or even a reversible cause. However, imaging screening for all individuals with headache is costly and unrewarding. Therefore, it is important to know the warning signs that, together with the clinical context, lead to a more precise indication of these exams and early and well-targeted therapeutic interventions. Clinical case: This is a 60-year-old man, previously dyslipidemic and smoker, with migraine with aura reported since childhood, who underwent treatment with sodium valproate, with headache attack suppression. About 4 months before admission, he presented with an alteration in the pain pattern, amaurosis fugax in the right eye, dizziness and mild paresis and hypoesthesia in the left side of the body, primarily treated by him as migraine crises, without improvement with the use of triptans. A new outpatient investigation was carried out, which showed multiple small infarcts in the right hemisphere secondary to atheromatous plaque in the right carotid bulb with an obstruction of approximately 85%. Diagnostic and therapeutic arteriography was performed, with stent implantation, uneventfully. Conclusion: The differential diagnosis between migraine with aura and a cerebrovascular event has already been widely reported in the literature and constitutes a pitfall in the routine of headaches, since a serious and potentially disabling condition can be overlooked. The joint evaluation of the alarm signs with the global context becomes an important tool in the propaedeutics of these patients, with knowledge of this casuistry being something relevant within clinical practice.

Introdução: A cefaleia é uma queixa muito comum nos consultórios médicos, sendo as causas primárias majoritárias em relação às secundárias. Apesar disso, a identificação de cefaleias secundárias é muito relevante na prática clínica, uma vez que estas podem ser uma condição potencialmente fatal, funcional ou mesmo uma causa reversível. No entanto, o rastreio imagiológico para todos os indivíduos com cefaleias é dispendioso e pouco recompensador. Portanto, é importante conhecer os sinais de alerta que, juntamente com o contexto clínico, levam a uma indicação mais precisa destes exames e a intervenções terapêuticas precoces e bem direcionadas. Caso clínico: Trata-se de um homem de 60 anos, previamente dislipidémico e fumador, com queixa de enxaqueca com aura desde a infância, que realizou tratamento com valproato de sódio, com supressão das crises de cefaleia. Cerca de 4 meses antes da internação apresentou alteração do padrão álgico, amaurose fugaz em olho direito, tontura e leve paresia e hipoestesia no lado esquerdo do corpo, tratada por ele primariamente como crises de enxaqueca, sem melhora com o uso de triptanos. Foi realizada nova investigação ambulatorial que evidenciou múltiplos pequenos infartos no hemisfério direito secundários a placa de ateroma no bulbo carotídeo direito com obstrução de aproximadamente 85%. Foi realizada arteriografia diagnóstica e terapêutica, com implante de stent, sem intercorrências. Conclusão: O diagnóstico diferencial entre enxaqueca com aura e evento cerebrovascular já foi amplamente relatado na literatura e constitui uma armadilha na rotina das cefaleias, uma vez que uma condição grave e potencialmente incapacitante pode ser negligenciada. A avaliação conjunta dos sinais de alarme com o contexto global torna-se uma ferramenta importante na propedêutica destes pacientes, sendo o conhecimento desta casuística algo relevante dentro da prática clínica.

Vestibular Function and Clinical Presentation of Dizziness: Are They Similar in Patients With Different Types of Migraine?

OBJECTIVE: To compare the vestibular function and clinical aspects (vestibular and migraine symptoms) of patients divided into three groups-migraine without aura, migraine with aura, and chronic migraine-and a control group by using electronystagmography and a design questionnaire. STUDY DESIGN: Case-control study. SETTING: Tertiary referral center. PATIENTS: Women aged between 18 and 55 years diagnosed with migraine with aura, migraine without aura, or chronic migraine according to the International Classification of Headache Disorders ICHD-third edition; diagnosis was made by a headache specialist. The control group consisted of patients' family members and hospital employees without a personal history of headache. MAIN OUTCOME MEASURES: Application of a questionnaire regarding vestibular symptoms and their relation to migraine aspects. Assessment of the vestibular function by electronystagmography. RESULTS: This study evaluated 120 female patients. Dizziness was the most prevalent vestibular symptom in all the migraine groups, with higher prevalence in the episodic migraine with aura and chronic migraine groups. Phonophobia and photophobia during vestibular symptoms also had greater prevalence in the latter groups. Electronystagmography tests did not reveal differences among the groups, but clinical stratification showed that tests with mixed etiology abnormalities were more prevalent in the episodic migraine with aura and chronic migraine groups. CONCLUSION: The prevalence of vestibular symptoms in the migraine groups and the etiology of vestibular impairment highlight that migraine affects the vestibular system. Our findings suggest that symptom progression and vestibular impact are related to migraine chronicity and presence of aura.

Physical activity pattern and migraine according to aura symptoms in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohort: A cross-sectional study.

OBJECTIVE: To estimate the associations of physical activity (PA) levels with migraine subtypes. BACKGROUND: Physical activity has been associated with reduced migraine prevalence, but less is known about its relationship with migraine subtypes and PA levels as recommended by World Health Organization (WHO). METHODS: In this cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we estimated the odds ratios (ORs) of migraine with aura (MA) and migraine without aura (MO), compared to participants without headaches, according to PA levels in the leisure time (LTPA), commuting time (CPA), and combined PA domains. RESULTS: In total, 2773 participants provided complete data, 1556/2773 (56.1%) were women, mean (SD) age of 52.3 (9.1) years. In this study's sample, 1370/2773 (49.4%) participants had overall migraine, 480/2773 (17.3%) had MA, and 890/2773 (32.0%) had MO. In the LTPA domain, there were reduced odds of MA (OR 0.72, 95% confidence interval [CI] 0.53-0.96; p = 0.030) and MO (OR 0.71, 95% CI 0.56-0.90; p = 0.005) in participants who met the WHO PA guidelines after adjustment for confounder variables. In the analyses stratified by intensity, moderate LTPA was associated with reduced odds of MA (OR 0.56, 95% CI 0.320-0.99; p = 0.049), while vigorous LTPA was associated with reduced odds of MO (OR 0.55, 95% CI 0.395-0.77; p = 0.001). There were no significant associations between migraine subtypes and CPA or combined PA domains. In the whole migraine sample, meeting the WHO PA guidelines in the LTPA (OR 0.275, 95% CI 0.083-0.90; p = 0.034), CPA (OR 0.194, 95% CI 0.064-0.58; p = 0.004), and combined domains (OR 0.115, 95% CI 0.032-0.41; p = 0.001) was associated with reduced odds of daily migraine attack frequency. CONCLUSIONS: Meeting the WHO PA guidelines for LTPA, but not CPA or combined PA domains, is associated with lower migraine occurrence. Moderate LTPA favors MA reduction, while vigorous LTPA favors MO reduction.

Migraine and balance impairment: Influence of subdiagnosis, otoneurological function, falls, and psychosocial factors.

OBJECTIVE: To assess the balance sensory organization among patients with migraine, considering the influence of migraine subdiagnosis, otoneurological function, falls, and psychosocial factors. BACKGROUND: Migraine has been associated with vestibular symptoms and balance dysfunction; however, neither comprehensive balance assessment nor associated factors for greater impairment have been addressed thus far. METHODS: Patients from a tertiary headache clinic with a diagnosis of episodic migraine with aura (MWA), without aura (MWoA), and chronic migraine (CM) were included for this cross-sectional study (30 patients per group). Thirty headache-free controls (CG) were recruited. Participants underwent a comprehensive evaluation protocol, including the Sensory Organization Test (SOT) and otoneurological examination. Questionnaires about fear of falls, dizziness disability, and kinesiophobia were administered. RESULTS: All migraine groups presented lower composite SOT scores than controls (CG: 82.4 [95% confidence interval (CI): 79.5-85.3], MWoA: 76.5 [95% CI: 73.6-79.3], MWA: 66.5 [95% CI: 63.6-69.3], CM: 69.1 [95% CI: 66.3-72.0]; p < 0.0001). Compared to controls and to MWoA, MWA and CM groups exhibited greater vestibular (CG: 75.9 [95% CI: 71.3-80.4], MWoA: 67.3 [95% CI: 62.7-71.8], MWA: 55.7 [95% CI: 51.2-60.3], CM: 58.4 [95% CI: 53.8-63.0]; p < 0.0001) and visual functional impairment (CG: 89.6 [95% CI: 84.2-94.9], MWoA: 83.2 [95% CI: 77.9-88.6], MWA: 68.6 [95% CI: 63.3-74.0], CM: 71.9 [95% CI: 66.5-77.2], p < 0.0001). Fall events during the assessment were documented more often among patients with migraine (CG: 0.0, interquartile range [IQR], 0.0, 0.0); MWoA: 1.0 [IQR: 1.0, 1.0], MWA: 2.0 [IQR: 1.8, 4.3], CM: 1.0 [IQR: 1.0, 2.0]; p = 0.001). The SOT scores correlated with fear of falls (r = -0.44), dizziness disability (r = -0.37), kinesiophobia (r = -0.38), and migraine frequency (r = -0.38). There was no significant influence of the vestibular migraine diagnosis in the study outcomes when used as a covariate in the analysis (composite score [F = 3.33, p = 0.070], visual score [F = 2.11, p = 0.149], vestibular score [F = 1.88, p = 0.172], somatosensory score [F = 0.00, p = 0.993]). CONCLUSIONS: Aura and greater migraine frequency were related to falls and balance impairment with sensory input manipulation, although no otoneurological alterations were detected. The diagnosis of vestibular migraine does not influence the balance performance. The vestibular/visual systems should be considered in the clinical examination and treatment of patients with migraine.

Recomendaciones de la Asociación Colombiana de Neurología para el uso de anticuerpos monoclonales antiCGRP en la profilaxis de migraña / Recommendations on the use of the antiCGRP monoclonal antibodies for migraine prophylaxis on behalf of the Colombian Association of Neurology

RESUMEN INTRODUCCIÓN: El desarrollo de anticuerpos monoclonales (mAbs) contra el péptido relacionado con el gen de la calcitonina (CGRP) ha determinado una nueva era terapéutica en la profilaxis de migraña, demostrando su efectividad en pacientes con migraña episódica (ME) y migraña crónica (MC), con respuesta desde pacientes naïve hasta refractarios a múltiples medicamentos. La disminución del 50% de los ataques de migraña al mes (DMM) durante los primeros 3 meses de uso es el desenlace aproximado en el 50% de los pacientes que reciben esta terapia. OBJETIVO: Este consenso de la Asociación Colombiana de Neurología (ACN) tiene el objetivo de guiar la selección y uso racional de los mAbs antiCGRP en pacientes con ME y MC. MATERIALES Y MÉTODOS: El comité de cefalea de la ACN mediante la aplicación de la metodología Delphi y discusiones en reuniones posteriores desarrolló un documento en formato de consenso soportado en literatura y recomendaciones de expertos. RESULTADOS: Se obtuvieron respuestas de 14 expertos en cefalea sobre moléculas utilizadas en profilaxis de migraña, analizando su aplicabilidad en situaciones clínicas frecuentes. DISCUSIÓN: Los mAbs antiCGRP han demostrado efectividad con adecuado soporte fisiopatológico, considerando que son moléculas de alto precio en una enfermedad de alta prevalencia, existe la necesidad de guíar la selección del paciente que mejor puede beneficiarse de su administración CONCLUSIONES: Los mAbs antiCGRP están recomendados en pacientes con ME y MC que presentan falla terapéutica a otras moléculas profilácticas.

ABSTRACT INTRODUCTION: The development of monoclonal antibodies (mAbs) against Calcitonin Gene Related Peptide (CGRP) has determined a new therapeutic era in migraine prophylaxis, demonstrating its effectiveness in patients with episodic migraine (EM) and chronic migraine (CM), obtaining a response in naive patients and in those who are refractory to multiple medications. A 50% decrease in migraine attacks per month during the first 3 months of use is the approximate outcome in 50% of patients receiving this therapy. OBJECTIVE: This consensus from the Colombian Association of Neurology (ACN) has the objective of serving as a guide for the rational use of antiCGRP mAbs in patients with EM and CM. METHODS AND MATERIALS: The headache committee through the application of the Delphi methodology and discussions in subsequent meetings, develops this consensus, supported in the published literature and expert recommendations. RESULTS: Fourteen answers from headache experts were received regarding the use of drugs for migraine prophylaxis, analyzing their applicability in frequent clinical situations. DISCUSSION: AntiCGRP mAbs have proved their effectiveness with adequate pathophysiological support, but with a high price in a highly prevalent disease, there is then a need to select the patient who best benefits from this therapy. CONCLUSIONS: AntiCGRP mAbs are recommended in patients with EM and CM that have previously failed to other prophylactic drugs.

The digiti quinti sign in hemiplegic migraine: An fMRI study.

BACKGROUND AND PURPOSE: The digiti quinti sign (DQS) consists of a wider angle between the fourth and fifth fingers (ANG) indicative of subtle hemiparesis that has been found interictally in hemiplegic migraine (HM), suggesting a permanent subtle motor dysfunction. The aim of this study was to find a possible cortical origin for the DQS using blood oxygen level dependent (BOLD) functional (f) MRI. METHODS: Eight HM patients and 13 controls entered the cross-sectional study. We examined hand dominance, performed handgrip tests with dynamometry, documented the DQS graphically in two consecutive sessions, and used BOLD-fMRI during a motor task specifically designed to measure the evoked activation in the motor cortex (M1). The brain activation at the symptomatic side was compared with the contralateral hemisphere and with both correspondent hemispheres in controls. RESULTS: Subjects had a normal neurological examination, except for DQS in all HM patients. The activation amplitude (beta values) and the cluster extension (mm3 ) of the activation area in M1 was smaller at the affected side. Besides, the cluster extension correlated negatively with the disease time span. The ANG was wider bilaterally in patients and the fMRI signals were reduced in the patient's group. CONCLUSION: The DQS, a relevant clinical finding in HM, indicates a disrupted cortical activation.

Tratamento homeopático de um caso de enxaqueca: relato de caso

A enxaqueca é uma doença de alta prevalência, com importantes repercussões nas atividades diárias dos indivíduos e de difícil tratamento na prática médica hegemônica. OBJETIVO: esta monografia visa relatar o caso de uma paciente do sexo feminino de 55 anos de idade portadora de enxaqueca há mais de 40 anos, que foi tratada sem sucesso pela terapêutica alopática. MÉTODO: as informações foram obtidas por meio de revisão do prontuário, entrevista com a paciente, pesquisa na Matéria Médica Homeopática e Repertório de Sintomas e revisão da literatura. CONSIDERAÇÕES FINAIS: o caso relatado e publicações levantadas trazem à luz a discussão da terapêutica homeopática de uma doença complexa como a enxaqueca. O presente estudo, apesar de relatar um caso ainda em andamento, mostra que a terapêutica homeopática é capaz de proporcionar resultados satisfatórios e duradouros no que diz respeito ao alívio sintomático e melhoria da qualidade de vida, quando comparado com a terapêutica hegemônica. (AU)

The objective of this paper is. Migraine is a highly prevalent disease, with important repercussions on individuals' daily activities and difficult to treat in hegemonic medical practice. OBJECTIVE: This monograph aims to report the case of a 55-year-old female patient with migraine for over 40 years, who was unsuccessfully treated by allopathic therapy. METHOD: the information was obtained through a review of the medical record, interview with the patient, research in the Homeopathic Materia Medica and Repertoire of Symptoms and literature review. FINAL CONSIDERATIONS: the case reported and publications raised bring to light the discussion of homeopathic therapy for a complex disease such as migraine. The present study, despite reporting a case still in progress, shows that homeopathic therapy is capable of providing satisfactory and lasting results with regard to symptomatic relief and improvement in quality of life, when compared to hegemonic therapy. (AU)

Migraine and Arterial Stiffness in the Brazilian Longitudinal Study of Adult Health: ELSA-Brasil.

BACKGROUND: The mechanisms that underlie the link between migraine and cardiovascular diseases are not clear and arterial stiffness could play a role in that association. We analyzed the association between migraine and vascular stiffness measured by carotid-to-femoral pulse wave velocity (PWV-cf). METHODS: In a cross-sectional analysis of a well-defined population from the Longitudinal Study of Adult Health (ELSA-Brasil) with complete and validated information about migraine and aura according to the International Headache Society criteria, the association between arterial stiffness measured by PWV-cf was tested with multiple linear regression models [ß (95% CI)] comparing migraine without aura (MO) and migraine with aura (MA) to the reference group no-migraine (NM). Subsequent adjustments were made for mean arterial pressure, age, sex, education level, physical activity, alcohol use, diabetes mellitus, smoking, antihypertensive medication, body mass index, waist circumference, triglycerides, and LDL-c level to test the independence of the association between migraine status and pulse wave velocity. RESULTS: We studied 4,649 participants, 2,521 women (25.7% MO and 15% MA) and 2,128 men (11% MO and 4.3% MA). In NM, MO, and MA standard PWV-cf were 8.67 (±1.71) 8.11 (±1.31) and 8.01 (±1.47) m/s, respectively. Unadjusted PWV-cf differed between NM, MA, and MO (P < 0.001). After adjustment for mean arterial pressure PWV-cf in NM did not differ anymore from MA (P = 0.525) and MO (P = 0.121), respectively. Fully adjusted models also yielded nonsignificant coefficients ß (95% CI) -0.079 (-0.280; 0.122) and -0.162 (-0.391; 0.067) for MO and MA, respectively. CONCLUSION: In this large cohort of middle-aged adults, aortic PWV was not associated with migraine.

Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations.

The Na+/K+- ATPase acts as an ion pump maintaining the essential plasma membrane potential in all mammalian cell types, and is essential for many cellular functions. There are four α isoforms (α1, α2, α3 and α4) with distinct expression patterns, kinetic properties and substrate affinity. The α2-isoform is encoded by ATP1A2 and evidence supports its utmost importance in Cl- homeostasis in neurons, and in the function of respiratory neurons at birth. Monallelic pathogenic variants in ATP1A2 are associated with familial hemiplegic migraine type 2 (FHM2) and on rare occasions with alternating hemiplegia of childhood 1 (AHC1). To date, no instances of biallelic loss of function variants have been reported in humans. However, Atp1a2 homozygous loss of function knockout mice (α2-/- mice) show severe motor deficits, with lack of spontaneous movements, and are perinatally lethal due to absent respiratory activity. In this report we describe three newborns from two unrelated families, who died neonatally, presenting in utero with an unusual form of fetal hydrops, seizures and polyhydramnios. At birth they had multiple joint contractures (e.g. arthrogryposis), microcephaly, malformations of cortical development, dysmorphic features and severe respiratory insufficiency. Biallelic loss of function variants in ATP1A2, predicted to be pathogenic were found on whole exome sequencing. We propose that this is a distinctive new syndrome caused by complete absence of Na+/K+- ATPase α2-isoform expression.

Arteriopatía cerebral autosómica dominante con infartos subcorticales yleucoencefalopatía / Autosomal dominant cerebral arteriopathy with subcortical infarctions and leukoencephalopathy

Objetivo: Describir la obtención del diagnóstico de la arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía, así como el tratamiento dado y la evolución de un paciente.Caso clínico: Paciente femenina de 44 años, con antecedentes de migraña, con aura típica desde los 25 años. Tenía antecedentes familiares de migraña, infartos cerebrales, muerte y discapacidad de origen neurológico en adultos jóvenes. Acudió con un cuadro clínico de encefalopatía aguda, que comenzó con cefalea migrañosa acompañada de vómitos, fotofobia, escotomas y, posteriormente, fiebre yalucinaciones. La imagen de resonancia magnética de cráneo mostró infartos lacunares e hiperintensidades en T2 en la sustancia blanca del polo temporal izquierdo. El electroencefalogramamostró actividad de base lenta. Se diagnosticó una arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía a través de la clínica, signos característicos en la neuroimagen, y la biopsia de piel. Se le indicó tratamiento con aspirina y acetazolamida. La paciente ha tenido una evolución favorable.Conclusiones: El análisis de las características clínicas, los hallazgos de neuroimagen y el examen pormicroscopia electrónica de la biopsia de piel permitieron el diagnóstico en la paciente de una arteriopatía cerebral autosómica dominante con infartos subcorticales y leucoencefalopatía. Se le indicó tratamiento farmacológico con el que la paciente ha tenido una evolución favorable(AU)

ABSTRACTIntroduction: CADASIL (Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is an autosomal dominant neurovascular disorder that causes ischemic subcortical stroke, migraine with aura, depression, apathy, and dementia. It have a variable prevalence(at least 2-10.7 per 100,000 adults) and is the most common cause of inherited stroke and vascular dementia in adults.Clinical case: Female patient aged 44 with a history of migraine with aura since age 25. Also, family history of migraine, stroke, death and disability in youngsters. She arrives with clinical picture of acute encephalopathy that begins with a migraine headache accompanied by vomiting, photophobia, scotoma and later fever and hallucinations. Brain MRI shows abnormalities such as several lacunar infarcts and T2 hyperintensities involving the white matter of the left anterior temporal pole. The EEG shows slow background. Diagnosis was confirmed with detection of eosinophilic inclusions in smooth muscle cell of dermic capillary of skin biopsy (osmophilic in transmission electronic microscopy).Conclusions: The patient showed is the first confirmed case in Cuba with CADASIL. Unfortunately, because of similarities in clinical presentation and neuroimaging, this disorder is often misdiagnosed as multiple sclerosis and treated with immunomodulatory medications that confer risk without benefit(AU)

[Typical visual aura without headache: a case report.] / Aura visual típica sin cefalea: a propósito de un caso.

Introduction: The typical aura without headache is a type of migraine with aura regularly assessed by ophthalmology. It is defined as at least two recurrent attacks, lasting from 5 to 60 minutes, of reversible, visual, sensorial and / or language unilateral neurological symptoms.Methods: We present a case report of a male with typical aura without headache. Results: Male with a history of migraine without aura in adolescence and without vascular risk factors. Referred from ophthalmology by biweekly episodes characterized by central teicopsia that progressively covers the entire visual field in 20 minutes, without being influenced by opening or closing eyes, which disappears after 40 minutes from the beginning. The episodes are not stereotyped, they are not followed by headache, nor do they associate other neurological symptoms. Neurological examination and complementary tests were normal. It is concluded in favor of typical aura without headache and after six months of starting treatment with Lamotrigine there were no recurrences. Final conclusion: The diagnosis of typical aura without headache begins with an adequate anamnesis. Due to the nature of its manifestations it is necessary to differentiate it from other etiologies such as transient ischemic attacks and focal seizures due to the diagnostic, therapeutic and prognostic implications. It may appear, as in this case, in patients with migraine without aura. Lamotrigine is an excellent therapeutic option in the typical aura without headache.

Introducción: El aura típica sin cefalea es un tipo de migraña con aura valorada al inicio regularmente por oftalmología. Se define como al menos dos ataques recurrentes, de 5 a 60 minutos de duración, de síntomas neurológicos unilaterales reversibles, visuales, sensoriales y/o lenguaje. Métodos: Presentamos el caso clínico de un varón con aura migrañosa sin cefalea. Resultados: Varón con antecedente de migraña sin aura en la adolescencia y sin factores de riesgo vascular. Remitido desde oftalmología por episodios bisemanales caracterizados por teicopsia central que progresivamente abarca todo el campo visual en 20 minutos, sin influenciarse con la apertura o cierre ocular, que desaparece tras 40 minutos desde el inicio. Los episodios no son estereotipados, no se siguen de cefalea, ni asocian otros síntomas neurológicos. La exploración neurológica y las pruebas complementarias fueron normales. Se concluye a favor de aura típica sin cefalea y tras seis meses de iniciar el tratamiento con Lamotrigina no existieron recurrencias. Conclusión final: El diagnóstico de aura típica sin cefalea inicia con una anamnesis adecuada. Por la naturaleza de sus manifestaciones se hace necesario diferenciarle de otras etiologías como accidentes isquémicos transitorios y crisis epilépticas focales por las implicaciones diagnósticas, terapéuticas y pronósticas. Puede aparecer, como en este caso, en pacientes con migraña sin aura. La lamotrigina es una excelente opción terapéutica en el aura típica sin cefalea.