Cutaneous Allodynia in Migraine: A Narrative Review

Cutaneous allodynia; Risk factors; TreatmentAlodinia cutánea; Factores de riesgo; TratamientoAlodínia cutània; Factors de risc; TractamentObjective: 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

Biomarcadores de migraña en resonancia magnética craneal avanzada

Objectiu: comparar en pacients i controlar el gruix i el volum de la matèria grisa i la difusivitat i anisotropia de la matèria blanca de les zones cerebrals relacionades amb la fisiopatologia de la migranya. Antecedents: Mètodes: Estudi analític observacional amb disseny de control de casos. Els pacients es van escanejar amb una imatge de ressonància magnètica de 1,5 T per fer el post-processament d'imatges de morfometria cortical (Statistical Parametric Mapping-12 i Freesurfer) i l'anàlisi microstructural de la substància blanca (imatge de tensió de difusió) de regions d'interès relacionades amb la fisiopatologia de migranya: còrtex somatosensorial, zones visuals (V3, MT +), hipotàlem, porció caudal del nucli sensorial del nervi trigeminal i protuberància del dorso-lateral. Es van recollir imatges entre atacs. Resultats: 128 pacients, 69 sense aura, 46 amb aura i 48 controls van mostrar un augment del volum de la matèria grisa del còrtex somatosensorial, una reducció del volumen de la substància grisa en la porció caudal del nucli sensible del nervi trigeminal. com a reducció de l'anisotropia fraccionada de la protuberància del dorso-lateral. Conclusions: Els pacients amb migranya presenten alteracions estructurals en regions d'interès relacionades amb la fisiopatologia de la migranya: porció caudal del nucli sensorial del nervi trigeminal i protuberància dorso-lateral, còrtex somatosensorial, aquesta última també està influenciada per la durada de la malaltia, que suggereix un substrat anatòmic alterat que es correlaciona amb la transmissió, modulació i percepció del dolor.Introducción: En los últimos años se han desarrollado estudios de neuroimagen que analizan si existen diferencias en sustancia gris y sustancia blanca en pacientes con migraña. Gran parte de ellos realizan un barrido generalizado cerebral para localizar áreas alteradas y disponen de muestras pequeñas. Métodos: Estudio analítico observacional con diseño de casos y controles. Se realizó RM craneal 1.5T a los pacientes y controles, extrayendo las secuencias eco-gradiente T1 3D y spin-eco planar, que permitieron realizar posteriormente el procesamiento de las imágenes de morfometría cortical (Mapeo Paramétrico Estadístico-12 y Freesurfer) y el análisis microestructural de la sustancia blanca (FSL) de regiones de interés relacionadas con la fisiopatología de migraña: corteza somatosensorial, áreas visuales (V3, MT+), hipotálamo, porción caudal del núcleo sensorial del nervio trigémino y protuberancia dorsolateral. Así mismo, se realizó tractografía probabilística de los hallazgos objetivados en la protuberancia dorsolateral. Resultados: 128 pacientes, 69 sin aura, 46 con aura y 48 controles mostraron un aumento en el volumen de la sustancia gris de la corteza somatosensorial esta última también está influenciada por la duración de la enfermedad, reducción en el volumen de sustancia gris en la porción caudal del núcleo sensitivo del nervio trigémino y reducción en la anisotropía fraccional de la protuberancia dorso-lateral. Conclusiones: Los pacientes con migraña presentan diferencias estructurales en regiones de interés relacionadas con la fisiopatología de la migraña, lo que sugiere un sustrato anatómico alterado en correlación con la transmisión, modulación y percepción del dolor.Objective: To compare in patients vs controls the thickness and volume of the gray matter and the diffusivity and anisotropy of the white matter of brain areas related to the pathophysiology of migraine. Background: Methods: Observational analytic study with case-control design. Patients were scaner on a 1.5T magnetic resonance image to do the post-processing of the cortical morphometry images (Statistical Parametric Mapping-12 and Freesurfer) and microstructural analysis of white matter (diffusion tensor image) of regions of interest related to the pathophysiology of migraine: somatosensory cortex, visual areas (V3, MT+), hypothalamus, caudal portion of the sensory nucleus of the trigeminal nerve and dorso-lateral protuberance. Imaging was collected between attacks. Results: 128 patients, 69 without aura, 46 with aura and 48 controls showed an increase in the volume of the gray matter of the somatosensory cortex, a reduction in gray matter volumen in caudal portion of the sensitive nucleus of the trigeminal nerve, as well as reduction in the fractional anisotropy of the dorso-lateral protuberance. Conclusions: Migraine patients present structural alterations in regions of interest related to the pathophysiology of migraine: caudal portion of the sensory nucleus of the trigeminal nerve and dorso-lateral protuberance, somatosensory cortex, the latter is also influenced by the duration of the disease, which suggests an altered anatomical substrate that correlates with the transmission, modulation and perception of pain

Biomarcadores de migraña en resonancia magnética craneal avanzada

Objectiu: comparar en pacients i controlar el gruix i el volum de la matèria grisa i la difusivitat i anisotropia de la matèria blanca de les zones cerebrals relacionades amb la fisiopatologia de la migranya. Antecedents: Mètodes: Estudi analític observacional amb disseny de control de casos. Els pacients es van escanejar amb una imatge de ressonància magnètica de 1,5 T per fer el post-processament d’imatges de morfometria cortical (Statistical Parametric Mapping-12 i Freesurfer) i l’anàlisi microstructural de la substància blanca (imatge de tensió de difusió) de regions d’interès relacionades amb la fisiopatologia de migranya: còrtex somatosensorial, zones visuals (V3, MT +), hipotàlem, porció caudal del nucli sensorial del nervi trigeminal i protuberància del dorso-lateral. Es van recollir imatges entre atacs. Resultats: 128 pacients, 69 sense aura, 46 amb aura i 48 controls van mostrar un augment del volum de la matèria grisa del còrtex somatosensorial, una reducció del volumen de la substància grisa en la porció caudal del nucli sensible del nervi trigeminal. com a reducció de l’anisotropia fraccionada de la protuberància del dorso-lateral. Conclusions: Els pacients amb migranya presenten alteracions estructurals en regions d’interès relacionades amb la fisiopatologia de la migranya: porció caudal del nucli sensorial del nervi trigeminal i protuberància dorso-lateral, còrtex somatosensorial, aquesta última també està influenciada per la durada de la malaltia, que suggereix un substrat anatòmic alterat que es correlaciona amb la transmissió, modulació i percepció del dolor.Introducción: En los últimos años se han desarrollado estudios de neuroimagen que analizan si existen diferencias en sustancia gris y sustancia blanca en pacientes con migraña. Gran parte de ellos realizan un barrido generalizado cerebral para localizar áreas alteradas y disponen de muestras pequeñas. Métodos: Estudio analítico observacional con diseño de casos y controles. Se realizó RM craneal 1.5T a los pacientes y controles, extrayendo las secuencias eco-gradiente T1 3D y spin-eco planar, que permitieron realizar posteriormente el procesamiento de las imágenes de morfometría cortical (Mapeo Paramétrico Estadístico-12 y Freesurfer) y el análisis microestructural de la sustancia blanca (FSL) de regiones de interés relacionadas con la fisiopatología de migraña: corteza somatosensorial, áreas visuales (V3, MT+), hipotálamo, porción caudal del núcleo sensorial del nervio trigémino y protuberancia dorsolateral. Así mismo, se realizó tractografía probabilística de los hallazgos objetivados en la protuberancia dorsolateral. Resultados: 128 pacientes, 69 sin aura, 46 con aura y 48 controles mostraron un aumento en el volumen de la sustancia gris de la corteza somatosensorial esta última también está influenciada por la duración de la enfermedad, reducción en el volumen de sustancia gris en la porción caudal del núcleo sensitivo del nervio trigémino y reducción en la anisotropía fraccional de la protuberancia dorso-lateral. Conclusiones: Los pacientes con migraña presentan diferencias estructurales en regiones de interés relacionadas con la fisiopatología de la migraña, lo que sugiere un sustrato anatómico alterado en correlación con la transmisión, modulación y percepción del dolor.Objective: To compare in patients vs controls the thickness and volume of the gray matter and the diffusivity and anisotropy of the white matter of brain areas related to the pathophysiology of migraine. Background: Methods: Observational analytic study with case-control design. Patients were scaner on a 1.5T magnetic resonance image to do the post-processing of the cortical morphometry images (Statistical Parametric Mapping-12 and Freesurfer) and microstructural analysis of white matter (diffusion tensor image) of regions of interest related to the pathophysiology of migraine: somatosensory cortex, visual areas (V3, MT+), hypothalamus, caudal portion of the sensory nucleus of the trigeminal nerve and dorso-lateral protuberance. Imaging was collected between attacks. Results: 128 patients, 69 without aura, 46 with aura and 48 controls showed an increase in the volume of the gray matter of the somatosensory cortex, a reduction in gray matter volumen in caudal portion of the sensitive nucleus of the trigeminal nerve, as well as reduction in the fractional anisotropy of the dorso-lateral protuberance. Conclusions: Migraine patients present structural alterations in regions of interest related to the pathophysiology of migraine: caudal portion of the sensory nucleus of the trigeminal nerve and dorso-lateral protuberance, somatosensory cortex, the latter is also influenced by the duration of the disease, which suggests an altered anatomical substrate that correlates with the transmission, modulation and perception of pain.Universitat Autònoma de Barcelona. Programa de Doctorat en Medicin

Cutaneous Allodynia in Migraine : A Narrative Review

In the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine. 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. 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. 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. 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

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