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

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.17.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days >= 30%,>= 50%,>= 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice

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

Neuropsychological deficits in patients with cognitive complaints after COVID-19

Background: While much of the scientific focus thus far has been on cognitive sequelae in patients with severe COVID-19, subjective cognitive complaints are being reported across the spectrum of disease severity, with recent studies beginning to corroborate patients’ perceived deficits. In response to this, the aims of this study were to (1) explore the frequency of impaired performance across cognitive domains in post-COVID patients with subjective complaints and (2) uncover whether impairment existed within a single domain or across multiple. Methods: Sixty-three patients with subjective cognitive complaints post-COVID were assessed with a comprehensive protocol consisting of various neuropsychological tests and mood measures. Cognitive test performance was transformed into T scores and classified based on recommended guidelines. After performing a principal component analysis to define cognitive domain factors, distributions of test scores within and across domains were analyzed. Results: Results revealed pervasive impact on attention abilities, both as the singularly affected domain (19% of single-domain impairment) as well as coupled with decreased performance in executive functions, learning, and long-term memory. These salient attentional and associated executive deficits were largely unrelated to clinical factors such as hospitalization, disease duration, biomarkers, or affective measures. Discussion: These findings stress the importance of comprehensive evaluation and intervention to address cognitive sequelae in post-COVID patients of varying disease courses, not just those who were hospitalized or experienced severe symptoms. Future studies should investigate to what extent these cognitive abilities are recuperated over time as well as employ neuroimaging techniques to uncover underlying mechanisms of neural damage

Post-COVID-19 fatigue: the contribution of cognitive and neuropsychiatric symptoms

Fatigue in its many forms of physical, mental, and psychosocial exhaustion is a common symptom of post-COVID-19 condition, also known as “Long COVID.” Persistent fatigue in COVID-19 patients is frequently accompanied by cognitive dysfunction and neuropsychiatric symptoms; however, less is known about the relationships between these components of post-COVID-19 condition and fatigue itself. Consequently, the present study sought to (1) distinguish the types of fatigue experienced by participants, and (2) investigate whether cognitive deficits across various domains and neuropsychiatric conditions predicted these different types of fatigue. The study included 136 COVID-19 patients referred for neuropsychological evaluation due to cognitive complaints 8 months on average after SARS-CoV-2 infection. Measures included self-reported fatigue (physical, cognitive, and psychosocial), neuropsychiatric questionnaires (assessing symptoms of depression, anxiety, apathy, and executive functioning), a comprehensive neuropsychological assessment, and self-reported quality of life and everyday functioning. Results showed that reports of clinical significant fatigue were pervasive in our sample (82.3% of participants), with physical fatigue rated highest on average relative to the subscale maximum. Elevated levels of apathy, anxiety, and executive dysfunction in neuropsychiatric measures along with executive and attentional difficulties on cognitive tests were found to be consistently important predictors among different types of fatigue. This implicates both cognitive and neuropsychiatric symptoms as predictors of fatigue in post-COVID-19 condition, and stresses the importance of a holistic approach in assessing and considering potential treatment for COVID-19 patients experiencing fatigue

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

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Abstract Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65–87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice. Graphical Abstrac