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

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

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

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

Evolving Trends in Neuropsychological Profiles of Post COVID-19 Condition: A 1-Year Follow-up in Individuals with Cognitive Complaints

Background: Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. More longitudinal studies are needed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. Methods: 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results: Impacts on cognitive test scores remain stable across assessments. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Conclusions: Cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. An effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time

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

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

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. 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. 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%). Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice. The online version contains supplementary material available at 10.1186/s10194-023-01585-2