Explore the vast range of titles available.

BackgroundCalcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response.CasesWe present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy.ConclusionThis case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.

BackgroundCGRP monoclonal antibodies (mAb) are an effective new preventative treatment for episodic and chronic migraine, with a favourable adverse event profile. In addition to its role in mediating migraine attacks, CGRP is widely expressed throughout the body and in general has an anti-inflammatory/immunoregulatory role. Thus, inhibitory CGRP may potentiate a pro-inflammatory state.Methods/ResultsWe present a case series of eight patients with new or worsened inflammatory pathology in close temporal association with the start of CGRP mAb therapy.ConclusionsThis case series provides novel insights on the potential molecular mechanisms and side-effect profile of CGRP inhibition and warrants vigilance in clinical practice.

Anodal current applied to the vestibular apparatus has previously been found to inhibit discharge from irregular vestibular afferents in squirrel monkeys. We wished to investigate whether anodal currents applied over the mastoid processes of human subjects would significantly reduce ongoing vestibular activity and thereby the size of galvanic-evoked vestibulospinal reflexes, measured by soleus electromyogram. Nine subjects were tested, of whom six subjects (five females, one male) provided data for the final analysis. Tonic anodal current was applied over one mastoid at 0 (baseline), 2, 4, 6 and 8 mA. The cathode was placed at C7. Superimposed on each intensity of tonic current were separate, short anodal currents of 4 mA, duration 20 ms, presented as 128 stimuli to the same side, and used to test vestibular responsiveness. These trials were then repeated with the anode overlying the contralateral mastoid. Short latency (SL) and medium latency (ML) reflexes were measured from the right soleus muscle. All six subjects used in the final analysis had readily identifiable reflexes to all stimuli. One-way ANOVA revealed no significant difference in the magnitude of the SL ( P=0.99) or ML ( P=0.96) components of the vestibulospinal reflexes across the group. Despite surface anodal currents of up to 8 mA, there was no consistent effect on the size of galvanic-evoked vestibulospinal reflexes. As 8 mA is close to the maximum intensity tolerated by volunteer subjects, our results indicate that anodal current applied over the mastoids is unlikely to be a useful means of suppressing vestibular function in human subjects.

Vestibular signals are known to have an important role in stance under specific conditions. Potentially these effects could be modulated by vestibular reflexes or by voluntary responses to perceived vestibular signals. Our preliminary aim was to confirm that vestibulospinal reflexes change in parallel with sway under different postural conditions, and then to determine whether any relationship was present between these reflexes and body sway within fixed postural conditions. Sixteen subjects (eight male, eight female) were tested in conditions assessing the effects of vision (eyes open or closed), support surface (firm or compliant), external support (with or without) and stance width (feet apart or together). Sway (centre of pressure) in the anteroposterior (AP) and mediolateral planes was measured using a force platform. A subgroup of 11 subjects (five male, six female) underwent testing to measure short (SL) and medium latency (ML) reflexes from soleus. Bipolar, transmastoid galvanic stimulation (1 mA, 200 ms) was administered while subjects stood in the most unstable of our conditions (eyes closed, compliant surface and feet together). In the final part, to assess possible perceptual contributions to body sway, short duration AP sway levels were measured and expressed in angular terms (sway in mrad, velocity in mrad s(-1)) in the 11 subjects for both our baseline (eyes open, firm surface and feet apart) and most unstable conditions. Average sway levels increased more than seven-fold between conditions and had significant, positive correlations with reported changes in mean vestibulospinal reflexes under similar conditions (overall r = 0.75, P < 0.001). However, the SL reflex for the subgroup of 11 subjects had a significant negative correlation (r = -0.71; P = 0.014) with the degree of AP sway in the condition with maximum reliance on vestibular inputs (eyes closed, compliant surface, and feet together). Under baseline conditions, 5/125 (4%) of the short-term AP sway displacements were above the threshold previously reported for the detection of imposed sway. In the unstable condition, when sway was increased, 43/138 (31%) of the short-term AP sway movements were above the threshold for perception of imposed body sway based on vestibular signals. Our results confirm that vestibulospinal reflexes appear to be acutely facilitated as body sway increases. For the most unstable condition, when non-vestibular information was absent or attenuated, subjects with larger SL reflexes had less AP sway, suggesting that the SL reflex acted to attenuate sway. Under the same condition, short duration sway levels increased such that 31% were above the previously published threshold for detection using vestibular afferents. We conclude that both vestibular reflexes and perceptual signals appear to have a specific role in the maintenance of upright stance, under conditions in which other sources of postural information are attenuated or absent.