David Fernández-Hernando

Background: Cluster headache (CH) is a type of headache that has a global prevalence of 0.5–3/1000 people, provokes severe, strictly unilateral pain through the first branch of the trigeminal nerve, and is associated with observable autonomous responses. CH provokes intense pain and decreases quality of life. Objective: In this study, we aimed to carry out a systematic review of the effectiveness of non-invasive neuromodulation of the vagus nerve in patients with cluster headaches, which was registered on PROSPERO No. CRD42021265126. Methods: Six databases were used from their date of inception to February 2023 to obtain studies with the group intervention of non-invasive neuromodulation of the vagus nerve for cluster headache, with outcomes based on pain attacks, duration, and disabilities. Data on the subjects, group intervention, main outcomes, and results were collected by two authors. Results: The search provided 1003 articles, with three clinical trials being eligible for inclusion in the review. The methodological quality scores ranged from 6 to 8 points (mean: 7.3, SD: 0.8) out of a maximum of 10 points. The post-treatment results showed some positive effects using n-VNS as a treatment for cluster headache, more specifically regarding cervical neuromodulation of the vagus nerve. Conclusions: The systematic review found moderate-to-high-quality evidence supporting that n-VNS and cervical n-VNS may have some positive effects at the end of the treatment being effective to relieve the frequency and intensity of cluster headaches. The poor quantity of studies available and the lack of homogeneity in the study protocols did not allow the pooling of data for a meta-analysis.

Background: Migraine is a type of primary headache that is accompanied by symptoms such as nausea, vomiting, or sensitivity to light and sound.Objective: The aim of this study was to conduct a systematic review on the effectiveness of non-invasive neuromodulation, auricular transcutaneous vagus nerve stimulation (at-VNS), and electro-ear acupuncture of the vagus nerve in patients with migraine headaches.Methods: Six databases were searched from inception to 15 June 2022 for clinical trials, in which at least one group received any form of non-invasive neuromodulation of the vagus nerve for managing migraine with outcomes collected on pain intensity and related disability. Data, including participants, interventions, blinding strategy, outcomes, and results, were extracted by two reviewers. The methodological quality was assessed with the PEDro scale, ROB, and Oxford scale.Results: The search identified 1,117 publications with nine trials eligible for inclusion in the review. The methodological quality scores ranged from 6 to 8 (mean: 7.3, SD: 0.8) points. Low-quality evidence suggests some positive clinical effects for the treatment of chronic migraine with 1 Hz with at-VNS and ear-electro-acupuncture compared with the control group at post-treatment. Some of the studies provided evidence of the relationship between chronic migraine and a possible positive effect as a treatment with at-VNS and the neurophysiological effects using fMRI. Six of the studies provided evidence using fMRI of the relationship between chronic migraine and a possible positive effect as a treatment with at-VNS and the neurophysiological effects. Regarding all included studies, the level of evidence with the Oxford scale was level 1 (11.17%), six studies were graded as level 2 (66.66%), and two studies were graded as level 3 (22.2%). With the PEDro score, five studies got a low methodological score < 5 and only four got a score superior to 5, being highly methodological quality studies. For ROB, most of the studies were high risk and only a few of them received a low risk of bias. The pain intensity, migraine attacks, frequency, and duration were measured by three studies with positive results at post-treatment. And only 7% reported adverse events using at-VNS. All studies reported results at a post-treatment period in their respective main outcomes. And all studies with fMRI provided strong evidence of the relationship between the Locus Coeruleus, Frontal Cortex, and other superior brain areas with the auricular branch of the Vagus nerve with at-VNS.Conclusion: Some positive effects regarding the effect of non-invasive neuromodulation, auricular transcutaneous vagus nerve stimulation (at-VNS), and electro-ear acupuncture of the vagus nerve on migraine is reported in the current literature, but there are not enough data to obtain strong conclusions.Systematic review registration: This systematic review was registered in the PROSPERO database (registration number: CRD42021265126).

Background: Tinnitus is the perception of sound in the absence of actual external stimuli. Other associated symptoms include frustration, annoyance, anxiety, depression, stress, cognitive dysfunction, insomnia, or emotional exhaustion. Objective: In this study, we aimed to conduct a systematic review and meta-analysis on the effectiveness of the non-invasive neuromodulation of the vagus nerve in patients with tinnitus. Methods: Six databases were searched from their date of inception to 15 June 2022 to identify clinical trials in which at least one group received any form of non-invasive neuromodulation of the vagus nerve for tinnitus management, with outcomes based on annoyance and related disability. Data on participants, interventions, blinding strategies, assessment outcomes, and results were extracted by two reviewers. Results: The search identified 183 articles with five clinical trials eligible for inclusion in the review and four for the meta-analysis. The methodological quality scores ranged from 6 to 8 (mean: 7.3, SD: 0.8) points. The meta-analysis identified a significant positive effect on THI post-treatment for unilateral auricular stimulation (hg = 0.69, 95% CI 0.06, 1.32) or transcutaneous nerve stimulation (hg = 0.51, 95% CI 0.1, 0.9) compared with a comparative group. No effect on loudness intensity was observed. Conclusion: The results of the meta-analysis suggest that the application of the non-invasive neuromodulation of the vagus nerve has a positive effect post-treatment in terms of related disability in patients with tinnitus, although its clinical relevance is low. No firm conclusions about the effect of the non-invasive neuromodulation of the vagus nerve on tinnitus are available based on the current literature.