IntroductionOn March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.ObjectiveTo conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.ResultsAutonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.ConclusionSymptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.

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ObjectiveIn the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine.BackgroundCA 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.MethodsWe 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.ResultsThe 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.ConclusionsCA 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.

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Antecedentes y objetivo: El péptido relacionado con el gen de la calcitonina (CGRP, por sus siglas en inglés), es un neuropéptido involucrado en la fisiopatología de la migraña que también es conocido por participar en la función del sistema respiratorio y en algunas enfermedades inmunológicas como la sepsis. Hemos analizado el impacto del uso de los antagonistas de CGRP en pacientes con migraña durante la pandemia de COVID-19, causada por el coronavirus SARS-CoV-2. Métodos: Estudio transversal multicéntrico desarrollado entre mayo y noviembre de 2020, en el que la Sociedad Española de Neurología distribuyó a nivel nacional una encuesta de la que recogimos datos sobre la presencia, características y gravedad de síntomas de COVID-19, entre los que se encontraba la cefalea, en pacientes con migraña tratados con anticuerpos monoclonales (AcM) anti-CGRP, y los comparamos con los de pacientes con migraña que no recibían dicho tratamiento. También realizamos un subanálisis de los pacientes con síntomas de COVID-19. Resultados: Identificamos 300 pacientes con migraña: 51,7% (155/300) recibían AcM anti-CGRP; 87,3% eran mujeres (262/300) y la edad media (desviación estándar) de la muestra fue de 47,1 (11,6) años. Un total de 41 pacientes (13,7%) cumplían los criterios diagnósticos de COVID-19, sin diferencias estadísticamente significativas entre los pacientes que recibían tratamiento con AcM anti-CGRP y los que no (16,1% y 11,0%, respectivamente, p = 0,320). De los pacientes con COVID-19, 48,8% (20/41) acudieron a urgencias y 12,2% (5/41) fueron hospitalizados. Igualmente, no se detectaron diferencias clínicas entre los pacientes que recibían dicho tratamiento y los que no. Conclusión: El tratamiento con AcM anti-CGRP es un recurso seguro en la práctica clínica y no se asocia a un mayor riesgo de COVID-19.

Background and objective CGRP, a neuropeptide involved in migraine pathophysiology, is also known to play a role in the respiratory system and in immunological conditions such as sepsis. We analyzed the impact of the use of CGRP antagonists in patients with migraine during the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus. Methods This is a multicentre cross-sectional study. From May to November 2020, through a national survey distributed by the Spanish Society of Neurology, we collected data about the presence of COVID-19 symptoms including headache and their characteristics and severity in patients with migraine treated with anti-CGRP monoclonal antibodies (mAb), and compared them with patients with migraine not receiving this treatment. We also conducted a subanalysis of patients with COVID-19 symptoms. Results We recruited 300 patients with migraine: 51.7% (155/300) were taking anti-CGRP mAbs; 87.3% were women (262/300). Mean age (standard deviation) was 47.1 years (11.6). Forty-one patients (13.7%) met diagnostic criteria for COVID-19, with no statistically significant difference between patients with and without anti-CGRP mAb treatment (16.1% vs 11.0%, respectively; P = .320). Of the patients with COVID-19, 48.8% (20/41) visited the emergency department and 12.2% (5/41) were hospitalised. Likewise, no clinical differences were found between the groups of patients with and without anti-CGRP mAb treatment. Conclusion Anti-CGRP mAbs may be safe in clinical practice, presenting no association with increased risk of COVID-19.

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Background Nummular headache (NH) is defined by the presence of localized pain circumscribed to a round or elliptical area of the scalp, with a well‐defined contour and a diameter of 1–6 cm. Although some evidence supports a peripheral mechanism, its etiopathogenesis remains unclear. Case We report the case of a 64‐year‐old man with high‐frequency episodic migraine who has used topiramate, beta‐blockers, flunarizine, and amitriptyline without effect. In the last 8 years he also had continuous pain in an oval area of the scalp, consistent with NH. Triptans were ineffective for this new pain, and preventive therapy with gabapentin and onabotulinumtoxinA in the painful area had no effect. NH remitted when the patient received monthly treatment with subcutaneous galcanezumab for his migraine. Conclusions Monoclonal antibodies against calcitonin gene‐related peptide (CGRP), in particular galcanezumab, might be an effective therapy in some patients with NH. CGRP may have a role in the etiopathogenesis of this headache, which warrants further investigation.