xRead - Episodic Vertigo (January 2026)

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15264610, 2024, 10, Downloaded from https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.14835 by University Of Michigan Library, Wiley Online Library on [21/10/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

HEADACHE

FIGURE 2 Count of definitive dizzy days (DDDs) by month, comparing placebo and galcanezumab arms ( N = 38). Error bars show the standard error. [Color figure can be viewed at wileyonlinelibrary.com ]

for the treatment of VM without a placebo arm. 21 They found that after 12weeks of treatment, venlafaxine reduced DHI scores by 31.0 points, and propranolol reduced DHI scores by 24.5 points; however, the difference was not significant (paired t -test p = 0.19). Flunarizine, a calcium channel blocker, was investigated in two placebo-controlled trials. Lepcha et al. analyzed 48 participants ran domized to either placebo or 10mg of flunarizine and found statisti cally significant improvements in both vertigo frequency and vertigo severity. 22 On the other hand, Yuan et al. analyzed 23 participants randomized to either placebo or flunarizine, and did not find any dif ferences, although arguably that study was underpowered. 23 To date, a handful of cohort studies have looked at CGRP treat ment for VM. In a retrospective review of 25 participants, Hoskins and Fife found that 21 participants reported some level of improve ment in their symptoms. 24 Lovato and colleagues examined 23 par ticipants treated with erenumab, and found an average reduction in DHI from 30.2 (SD 7.2) to 8.1 (SD 3.1; Mann–Whitney U test; p < 0.0001), a reduction in migraine days, and elimination of posi tional nystagmus in 10 of 11 participants. 25 Finally, Russo et al. con ducted a prospective cohort study of 50 participants with a variety of anti-CGRP monoclonal antibodies. 13 Participants were asked to complete a daily diary documenting vertigo/dizziness and headache. They found that the number of days per month with vestibular symp toms decreased from 10.3 (SD 1.9) to 6.4 (SD 1.4) after 3months of treatment ( p < 0.001). They were able to follow some participants much longer and found that days with vestibular symptoms contin ued to decline at 6 months, 9 months, 1 year, finally reaching 0.7 days (SD 0.2days) by 18months. Our study adds to these cohort studies by providing stronger evidence for the efficacy of anti-CGRP treat ment with a placebo-controlled, randomized clinical trial. The pathophysiology of VM is not completely understood. Our results suggest that CGRP is involved in the generation of dizziness

and other symptoms of VM. Further research is needed to under stand the site of activity and mechanism of action. CGRP expression is anatomically complex and includes many structures that are part of the peripheral and central vestibular system: vestibular sensory organs, vestibular nucleus, cerebellum, thalamus, hippocampus, and cortical regions. 26 CGRP knockout mice show alterations of vestib ular reflexes, and CGRP infusion into mice causes impaired balance and nausea. 14,15,27 Therefore, it is possible that CGRP blockade in terrupts trigeminovascular inflammatory pathways that are present in the inner ear. Zhang et al. used a nitroglycerin-based rat model of chronic mi graine to investigate mechanisms of vestibular dysfunction. 28 They found that CGRP expression was elevated in the trigeminal nucleus caudalis and the vestibular nucleus in the chronic migraine rats, compared to controls. 29 These animals showed hyperalgesia and de creased vestibular function. Lentiviral vectors with CGRP RNA were then used to knock down CGRP in the chronic migraine rats, and this ameliorated hyperalgesia and vestibular dysfunction. VM is one of the most common causes of dizziness and vertigo, if not the most common. 1 Despite that, there is evidence of underdi agnosis, and many patients and providers lack understanding of this disease. 30 Large, prospective, placebo controlled randomized clinical trials are required to further investigate the efficacy of various mi graine treatments for VM. In addition to the obvious benefits of as certaining which treatments are effective, this would also help with educating the public and medical personnel regarding this common disease. Furthermore, there are still fundamental questions regard ing the relationship of VM to migraine headaches. This study adds to a body of evidence that VM is just another form of migraine and that the pathophysiology involves CGRP. This study included both participants with VM and probable VM to increase generalizability. However, 89% of participants in the mITT