Objective
The objective of this study was to analyze the evolution of alpha and beta‐CGRP circulating levels throughout CGRP monoclonal antibodies (mAbs) treatment in patients with chronic migraine ...(CM).
Methods
We recruited patients with CM beginning mAbs along with sex and age paired healthy controls (HCs). Blood was extracted before, 2 weeks (M0.5) and 3 months (M3) after the first dose of mAbs, always in free‐migraine periods, and once for HCs. Alpha and beta‐CGRP serum levels were measured using enzyme‐linked immunosorbent assays (ELISAs) specific for each isoform.
Results
Baseline alpha‐CGRP levels were significantly elevated in 103 patients with CM (median = 50.3, 95% confidence interval CI = 40.5–57.0 pg/ml) compared to 78 HCs (median = 37.5, 95% CI = 33.9–45.0 pg/ml; 95% CI of differences = 2.85–17.08 pg/ml) and significantly decreased (n = 96) over the course of mAb treatment (M0.5: median = 40.4, 95% CI = 35.6–48.2 pg/ml; and M3: median = 40.9, 95% CI = 36.3–45.9 pg/ml). Absolute decrease of alpha‐CGRP throughout the treatment positively correlated with the decrease in MMDs. Negative modulation of alpha‐CGRP significantly associated with positive scores at the Patient Global Impression of Change scale and with analgesic overuse reversal. Beta‐CGRP did not differ at baseline between patients with CM (median = 4.2, 95% CI = 3.0–4.8 pg/ml) and HCs (median = 4.4, 95% CI = 3.4–5.6 pg/ml; −1.09 to 0.60) nor was modulated by mAb treatment (n = 96; M0.5: median = 4.5, 95% CI = 3.5–5.2 pg/ml; and M3: median = 4.6, 95% CI = 3.7–5.2 pg/ml).
Interpretation
Treatment with mAbs, regardless of its target, is able to progressively normalize basally increased alpha‐CGRP levels in CM and this effect correlates with efficacy measures, which supports a role of this neuropeptide as the first CM biomarker. ANN NEUROL 2023;94:285–294
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.
Objective
To analyze the specificity of calcitonin gene–related peptide (CGRP) levels, we measured alpha‐CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory ...bowel disease (IBD) who were interviewed regarding comorbid headache.
Background
Several studies have found an association between migraine and IBD.
Methods
In this cross‐sectional study performed in an IBD clinic, morning serum alpha‐CGRP levels were measured by enzyme‐linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC).
Results
Alpha‐CGRP levels were higher in patients with IBD (median interquartile range 56.9 35.6–73.9 pg/mL) and patients with CM (53.0 36.7–73.9 pg/mL) compared to HC (37.2 30.0–51.8 pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha‐CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 35.6–73.4 pg/mL) and Crohn's disease (54.9 ± 27.5 pg/mL; 57.7 29.1–76.1 pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha‐CGRP levels were further different in patients with IBD with migraine (70.9 51.8–88.7 pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 33.3–73.8 pg/mL; p = 0.049), and patients with IBD with tension‐type headache but without migraine (41.7 28.5–66.9 pg/mL; p = 0.004), though alpha‐CGRP levels in patients with IBD without migraine (53.7 32.9–73.5 pg/mL) remained different over HC (p = 0.028).
Conclusion
Together with CM, circulating alpha‐CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha‐CGRP levels are not a totally specific migraine biomarker. However, alpha‐CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities.
Plain Language Summary
Alpha‐calcitonin gene–related peptide (CGRP) levels may be a potential migraine biomarker, but it is unclear if this is the case because changes in CGRP concentrations can also be present in other conditions. We measured morning serum alpha‐CGRP levels in 96 patients with a recent inflammatory bowel disease (IBD) diagnosis, and compared them to 50 matched healthy participants and 50 matched patients with chronic migraine (CM). We found a significant increase in serum alpha‐CGRP levels in both patients with IBD and CM compared to healthy controls, which we think may reflect chronic inflammation found in IBD; these results offer another example that alpha‐CGRP concentrations are not totally specific for migraine.
Other Primary Headaches: An Update González-Quintanilla, Vicente; Pascual, Julio
Neurologic clinics,
11/2019, Letnik:
37, Številka:
4
Journal Article
Recenzirano
"Other Primary Headaches" in the ICHD-3 encompasses activity-related headaches, headaches due to direct physical stimuli, epicranial headaches and a miscellanea, including hypnic headache and new ...daily-persistent headache. They can be primary or secondary and their etiologies differ depending on headache type. For instance, activity-related headaches can be induced by Valsalva maneuvers ("cough headache") or prolonged exercise ("exercise and sexual headaches"). Almost half of cough headaches are secondary to posterior fossa abnormality, whereas only 20% of exertional/sexual headaches are secondary, with subarachnoid hemorrhage the most frequent etiology. This article reviews the clinical diagnosis and management of these heterogeneous headaches.
Abstract
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.
Headache is among the most frequent symptoms of acute COVID-19 infection. Its mechanisms remain obscure, but due to its migraine-like characteristics, the activation of the trigeminal system could ...account for its underlying pathophysiology.
Our aim was to compare the serum levels of CGRP, as a theoretical marker of trigemino-vascular activation, in 25 COVID-19 inpatients with lung involvement experiencing headache, against 15 COVID-19 inpatients without headache and with those of 25 matched healthy controls with no headache history.
Morning serum alpha-CGRP levels, as measured by ELISA (Abbexa, UK), were increased in COVID-19 patients with headache (55.2±34.3 pg/mL) vs. controls (33.9±14.0 pg/mL) (p < 0.01). Alpha-CGRP levels in COVID-19 patients without headache were also significantly increased (43.3 ± 12.8 pg/mL; p = 0.05) versus healthy controls, but were numerically lower (-28.2%; p = 0.36) as compared to COVID-19 patients with headache.
CGRP levels are increased in COVID-19 patients experiencing headache in the acute phase of this disease, which could explain why headache frequently occurs in COVID-19 and strongly supports a role for trigeminal activation in the pathophysiology of headache in this viral infection.
The central nervous system was thought to be devoid of lymphatics. Recently, the existence of an authentic brain lymphatic system, known as the glymphatic system, composed of paravascular channels ...penetrating arterial and venous brain vessels and dural lymphatics cleaning the interstitial space, has been demonstrated. Aquaporin-4, located in astrocyte feet attached to the paravascular spaces, plays a key role in the clearance of waste molecules, such as beta-amyloid or tau proteins. The activity of this system is increased during sleep, mainly in the slow wave phase and while sleeping on one side, and with exercise, and is reduced with aging. Even though data are still preliminary, the glymphatic system could be decisively involved in the pathophysiology of neurological disorders such as neurodegenerative and demyelinating diseases, normal pressure hydrocephalus, stroke or certain headaches. The discovery of this system should provide new opportunities for the treatment of these neurological disorders.
Background
Some studies have suggested an association between migraine and inflammatory bowel disease. We determined migraine prevalence in a cohort of patients with inflammatory bowel disease.
...Methods
Patients with inflammatory bowel disease aged 18–65 years were interviewed using an ad hoc headache questionnaire. Those who admitted a history of headache in the last year answered the three questions of the ID-Migraine questionnaire. Those who answered “yes” to the three of them were classified as “definite” and those who answered “yes” to two were classified as “probable” migraine.
Results
We interviewed 283 patients with inflammatory bowel disease. Of these, 176 (62.2%) had headache. Fifty-nine (20.8%; 95% CI 16.3–26.0%) met migraine criteria either definite (n = 33; 11.7%; 95% CI 8.2–16.0%) or probable (n = 26; 9.2%; 95% CI 6.1–13.2). When divided by gender, 12 men (9.6%; 95% CI 5.1–16.2%) and 47 women (29.8%; 95% CI 22.8–37.5%) met migraine criteria. The prevalence of migraine was increased in inflammatory bowel disease patients from the current cohort (20.8%) versus that reported for our general population for the same age group (12.6%; p < 0.0001). These differences remained significant in female inflammatory bowel disease patients (29.8% versus 17.2% in our general population; p < 0.0001), but not in males (9.6% in inflammatory bowel disease vs 8.0%; p = 0.30). Seventeen patients with inflammatory bowel disease (6.0%; 95% CI 3.54–9.44%) fulfilled chronic migraine criteria. There were no differences in migraine prevalence by inflammatory bowel disease subtypes.
Conclusion
Migraine prevalence, including chronic migraine, seems to be increased in patients with inflammatory bowel disease. The fact that this association was stronger for women suggests an influence of sex-related factors.
