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Vasoactive peptides play an important role in a wide range of physiological and pathological conditions. Due to its known functions, the calcitonin gene-related peptide (CGRP) has been suggested as a possible modulator of the hyperimmune response in COVID-19 and thus, blocking its action may lessen the pulmonary effects of COVID-19.To compare the circulating levels of CGRPα and CGRPβ in healthy controls compared to hospitalized COVID-19 patients. The study also analyzed how different comorbidities and treatments may affect these concentrations in cases of COVID-19 infection with pulmonary involvement METHODS: Serum samples were collected from the antecubital vein of 51 control subjects (mean age = 55 ± 14 years; range = 26-77; 56.9% female) and 52 patients hospitalized with COVID-19 infection (mean age = 55 ± 13; range = 23-77; 55.8% female) from December 2020 to May 2021. Enzyme-linked immunosorbent assays (ELISAs) were used for CGRPα (Abbexa, UK) and CGRPβ (CUSABIO, China) measurements. Comorbidities, symptoms, and treatments of infection were listed.The results showed that the serum levels of both isoforms of CGRP were significantly higher in patients with COVID-19 (α: 57.9 ± 35.8 pg/mL; β: 6.1 ± 2.6 pg/mL) compared to controls (α: 41.8 ± 25.4 pg/mL; β: 4.5 ± 2.4 pg/mL) (p0.01). Also, the presence of arterial hypertension (HT), obesity, or corticosteroid treatment significantly alter the serum concentration of CGRPα in the subgroups compared to controls.The elevated serum CGRP levels found in our COVID-19 group compared to controls may suggest that CGRP plays a role in the pathophysiology of the disease, more specifically, in the cytokine storm and in the pulmonary involvement. Future studies should focus on the source of this CGRP elevation.

Background One of the advantages of CGRP monoclonal antibodies is their excellent safety and tolerability. However, postmarketing surveillance, is essential to detect potential rare emergent adverse events. Objectives To report two patients who developed restless legs syndrome symptoms after treatment with CGRP antibodies. Methods and results Two women with chronic refractory migraine, with no significant medical antecedents, developed typical restless legs syndrome symptoms 1.5 and 4 months after starting erenumab 140 mg, respectively. In case 1 symptoms resolved when erenumab was stopped for two months but reappeared on galcanezumab. In both patients migraine attacks had dramatically decreased and no iron deficiency was found. Conclusions Even though caution is needed before establishing a causal relationship, these cases suggest that restless legs-like symptoms might be an emergent adverse event of CGRP antibodies, regardless of the mechanism of action. We propose that plastic changes in CGRP sensory fibers, which are very abundant in legs, induced by CGRP monoclonal antibodies could be the reason for restless legs syndrome development.

Background: There are few published series of cluster headache. Our aim was to longitudinally describe the epidemiological and clinical features of cluster headache patients in our region since 1980.Methods: Retrospective analysis of the clinical charts of patients diagnosed as cluster headache in a Spanish tertiary hospital.Results: 153 patients were included. 137 (89,5%) were males. Mean age at the beginning of symptoms and diagnosis was 32.8 years (mean deviation 11.3) and 39.5 years (mean deviation 11.4) respectively. 128 had episodic cluster headache (92.2% males) and 25 chronic cluster headache (76% males). Mean age at the beginning was delayed in chronic cluster headache versus episodic cluster headache (37.6 vs 31.8 years; p= 0.023). Four patients (2.6%) had familial antecedents. 3 (2%) referred to visual aura. At diagnosis, 66% were smokers and 15% heavy alcohol drinkers. Median duration of cluster period and median frequency was 60 days every 2 years. 16 (10.5%) had only one cluster period during follow-up.Conclusion: Theoretical prevalence of cluster headache in our area was 0.05%. The diagnostic delay close to 7 years indicates an insufficient recognition of this entity. A late beginning and being a woman were associated with chronic cluster headache, while one out of ten patients only experienced one cluster period.

Background Headaches associated with physical exertion include headache precipitated by coughing or other Valsalva maneuvers, headache brought on by prolonged physical exercise, sexual headaches and cardiac cephalalgia. Objective To review and update the clinical characteristics, etiologies, pathophysiology and management of these headaches related to exertion. Methods In depth review of the publications, both in PubMed and in the main textbooks, of the different headaches induced by physical exercise. Results Cough, exercise and sexual headaches can be primary or secondary; therefore, complementary studies are mandatory to rule out structural lesions. However, clinical characteristics, such as an old age and response to indomethacin for cough headache or being a young male and response to beta-blockers for exercise and sexual headaches, plus a normal examination are suggestive of a primary etiology. Etiology for secondary varieties, as posterior fossa lesions for cough headache or vascular malformations for exercise and sexual headaches, are also different. Finally, headache as a distant manifestation of myocardial ischemia, also known as “cardiac cephalalgia”, appears at exertion in around two-thirds of cases and typically lasts less than 30 minutes and is relieved by nitroglycerine. Conclusions Primary and secondary cough headache can usually be suspected based on clinical characteristics and separated from exercise and sexual headaches, which share many aspects. Cardiac cephalalgia is not necessarily an exertional headache and should be considered in adult patients with short lasting headaches and patent vascular risk factors.

Background: Carriers of the G2019S mutation of LRRK2 provide a great opportunity to investigate the premotor stages of Parkinson's disease (PD). We have studied by serial clinical and dopamine transporter single photon emission computed tomography (DaT-SPECT) evaluations a cohort of asymptomatic carriers of the LRRK2-G2019S mutation in order to evaluate the usefulness of these tools as biomarkers. Here we report the results of the extended follow-up of this cohort at 8 years. Methods: Seventeen participants, of the 25 available from the 4-year evaluation, completed the 8-year assessment. UPDRS-III, UPSIT test and DaT-SPECT imaging (123I-ioflupane) were performed. We used repeated-measures linear mixed effects models to examine the changes in DaT binding over time. Results: Three carriers had converted to PD at 4 years. One additional carrier converted at 8 years. PD-converters had lower striatal DaT binding at baseline than non-converters. There was a significant decline of DaT binding over time, with a mean annual rate of 3.5%, with somewhat inter-individual and intra-individual variability and comparable between PD-converters and non-converters. No carrier with DAT binding ratio above an undefined threshold between 0.5 and 0.8 developed PD symptoms. The age-adjusted UPSIT score did not change significantly over time. Conclusions: The rate of conversion to PD at 8 years in this cohort aged ~58 years at baseline was 16%. The observed decline of DaT binding over time and its association with the phenotype render DaT-SPECT a potentially useful tool for monitoring the premotor stage of the disease, although at the individual level its ability to predict phenoconversion is limited.

Many patients with chronic migraine are difficult to treat. We present a patient with chronic migraine with good response to onabotulinum toxin type A whose headaches worsened in clear temporal relationship to local treatment with glyceryl trinitrate for an anal fissure. Our case shows that the use, even at distance, of nitric oxide donors can be a precipitating factor for migraineurs and should be always inquired in chronic migraine patients. In addition, the presence of frequent headaches should always be ruled out before prescribing such medications.