Headache Related Alterations of Visual Processing in Migraine Patients.

peer reviewedMigraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high-frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low beta). We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients. Visual evoked potentials from 20 healthy controls and 70 migraine patients (30 interictal and 20 ictal episodic migraineurs, 20 chronic migraineurs) were analyzed in the frequency domain. We compared power in the theta-alpha-low beta and gamma range between groups, and searched for correlations between the low-to-high frequency activity ratio and number of monthly headache and migraine days. Compared to healthy controls, interictal migraine patients had increased visually induced low frequency (feedback) activity. Conversely, ictal and chronic migraine patients showed an augmented gamma band (feedforward) power. The low-frequency-to-gamma (feedback/feedforward) activity ratio correlated negatively with monthly headache days and tended to do so with migraine days. Our findings show that visual processing is differentially altered depending on migraine cycle and type. Feedback control from higher order cortical areas predominates interictally in episodic migraine while migraine attacks and chronic migraine are associated with enhanced incoming afferent activity, confirming their similar electrophysiological profile. The presence of headache is associated with proportionally higher gamma (feedforward) activities. PERSPECTIVE: This study provides an insight into the pathophysiology of migraine headache from the perspective of cortical sensory processing dynamics. Patients with migraine present alterations in feedback and feedforward visual signaling that differ with the presence of headache

Evidence of activation of vagal afferents by non-invasive vagus nerve stimulation: An electrophysiological study in healthy volunteers

Background Benefits of cervical non-invasive vagus nerve stimulation (nVNS) devices have been shown in episodic cluster headache and preliminarily suggested in migraine, but direct evidence of vagus nerve activation using such devices is lacking. Vagal somatosensory evoked potentials (vSEPs) associated with vagal afferent activation have been reported for invasive vagus nerve stimulation (iVNS) and non-invasive auricular vagal stimulation. Here, we aimed to show and characterise vSEPs for cervical nVNS. Methods vSEPs were recorded for 12 healthy volunteers who received nVNS over the cervical vagus nerve, bipolar electrode/DS7A stimulation over the inner tragus, and nVNS over the sternocleidomastoid (SCM) muscle. We measured peak-to-peak amplitudes (P1-N1), wave latencies, and N1 area under the curve. Results P1-N1 vSEPs were observed for cervical nVNS (11/12) and auricular stimulation (9/12), with latencies similar to those described previously, whereas SCM stimulation revealed only a muscle artefact with a much longer latency. A dose-response analysis showed that cervical nVNS elicited a clear vSEP response in more than 80% of the participants using an intensity of 15 V. Conclusion Cervical nVNS can activate vagal afferent fibres, as evidenced by the recording of far-field vSEPs similar to those seen with iVNS and non-invasive auricular stimulation. </jats:sec

METABOLIC CHANGES IN THE MIGRAINE BRAIN IN RELATION TO AGEING AND DISEASE LOAD

Introduction: Migraine prevalence tends to decrease with advancing age. Morphological and functional brain changes occuring in migraine could be secondary to repeated attacks and/or to abnormal sensory processing. In normal ageing, brain modifications could traduce a progressive refinement to cope with the environment, associated with a reduction in the complexity of brain connections. We hypothesized that metabolism in various brain regions might be differentially modified by age in migraine patients. Materials and methods: Forty-one subjects underwent a FDG-PET scan: 21 patients with interictal episodic migraine without aura (MO, age range: 20–63 years, 5M) and 20 healthy controls (HV, 21–59 years, 5 M). Results: In MO vs. HV, the overall FDG uptake was reduced in the left visual cortex, left medial frontal gyrus and bilaterally in the insula, somatosensory and motor cortices. Metabolisms of the posterior thalamus, brainstem including the periaqueductal gray (PAG), visual cortex, and (para)hippocampus, strongly increased with age in MO patients but not in HV. Disease duration positively correlated with PAG, (para)hippocampus and rostral anterior cingulate cortex (rACC) metabolisms in MO. Conclusion: Migraine patients, compared to HV, have a decreased resting metabolism in several areas belonging to the ‘‘pain/salience matrix’’, which is in line with previous neuroimaging studies. Metabolism of the rACC is specifically related to disease load whereas metabolism of other sensory processing regions is more affected by age. Whether these functional changes are due to repeated stereotyped attack-related stimulations and to a learning process with complexity reduction of neuronal connections and/or compensatory age-related hyperactivity, remains to be demonstrate

Erenumab for Migraine Prevention in a 1-Year Compassionate Use Program: Efficacy, Tolerability, and Differences Between Clinical Phenotypes.

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) (n = 80) to chronic migraine (CM) (n = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) (p = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment (p < 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) (p < 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) (p < 0.05). There was no significant efficacy difference between low (4-7 migraine days/month, n = 22) and high frequency (8-14 days, n = 59) EM nor between patients with CM with (n = 50) or without (n = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies

DOES REGIONAL SOLAR RADIATION INFLUENCE HABITUATION OF VISUAL EVOKED POTENTIALS IN MIGRAINE? A TENTATIVE HYPOTHESIS BASED ON RETROSPECTIVE LITERATURE ANALYSIS

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Non-invasive vagus nerve stimulation with the gammaCore® in healthy subjects: is there electrophysiological evidence for activation of vagal afferents ?

Abstract: Background Non-invasive vagus nerve stimulation (nVNS) with the gammaCore® improves migraine and cluster headache. Animal experiments suggest that nVNS acts via stimulation of vagal afferents, but proof in humans is lacking. Vagal somatosensory evoked potentials (vSEP) are identified after invasive VNS or transcutaneous stimulation of auricular vagal branches, but late components could be muscle artifacts. Objective To search in healthy volunteers for reliable vSEP during nVNS with the gammaCore® Methods In 12 healthy subjects (7males) evoked potentials were recorded at A1/A2 (ref Cz) and C3/C4 (ref F3/F4) during 2-minute stimulation over left/right cervical vagus nerve with the gammaCore® (25Hz, 6-24V) and during stimulation over the inner tragus with a monopolar stimulator (2Hz, 50 stimuli, mean intensity 8mA). Results We identified 3 reproducible peaks P1, N1, P2 in 10 patients on the side of the gammaCore® stimulation at mean latencies of 2.05ms, 5.20ms and 9.13ms. P1-N1 amplitude increased significantly (p<0.01) with increasing voltage from 0.04μV to 0.52μV (C3/C4) and from 0.13µV to 2.04μV (A1/A2) respectively at 10V and 30V. Inner tragus stimulation elicited P1, N1, P2 peaks with shorter mean latencies (2.21ms, 3.72ms, 5.71ms) and a mean P1-N1 amplitude (A1/A2) of 5.0µV. When the gammaCore® was placed over the sternocleidomastoid muscle, there were no reproducible evoked potentials. Conclusion Non-invasive transcutaneous stimulation of the cervical vagus nerve with the gammaCore® elicits evoked potentials similar to those found with implanted electrodes or stimulation of Arnold’s nerve in the outer ear. The gammaCore®-evoked potentials increase in amplitude with stimulation intensity and disappear when the stimulator is positioned over neck muscles, suggesting that they are not muscle artifacts. Their short latency is compatible with their generation at the level of the foramen jugulare. The therapeutic effects reported with the gammaCore® in primary headaches can thus be mediated by genuine activation of vagus nerve afferents

Anodal transcranial direct stimulation (tDCS) targeting the anterior cingulate gyrus for the preventive treatment of chronic cluster headache: a proof of concept trial.

Background There is a need for better treatments in chronic cluster headache (CCH). In responders to percutaneous occipital nerve stimulation, the subgenual anterior cingulate gyrus (sACG) was found hypermetabolic (Magis et al. 2011). We reasoned that activation of this area by transcranial neurostimulation could be effective in CCH. Aim To explore the preventive effect of anodal (i.e. activating) transcranial direct current stimulation (tDCS) targeting the anterior cingulate gyrus in CCH patients. Method & subjects Difficult-to-treat CCH patients with a stable preventive drug regimen applied tDCS (2mA) interictally in 20-minute daily sessions for 4 weeks with the anode positioned over the forehead (FpZ), the cathode over the C7 spinous process. Therapeutic effects were monitored with paper diaries. Results Nineteen patients were enrolled up to now. In 13 patients who completed the trial, mean weekly attack frequency decreased by 38% after 4 weeks of daily stimulation (W-test: p = 0.002). The 50% responder rate was 54%. Patients (n=12) reported an improvement in headache impact, as shown by 5-point decrease in the mean HIT-6 score (from 67 to 62, p = 0.02). In 10 patients who were followed up after the treatment period, the benefit remained stable up to 4 weeks after the last stimulation. The first 3 enrolled patients had superficial skin burns under the adhesive cathode electrode. Sponge electrodes were therefore used in all subsequent patients without any adverse effect. Conclusion Anodal tDCS targeting the anterior cingulate gyrus seems promising for the preventive treatment of chronic cluster headache as suggested by this ongoing proof-of-concept trial. Use of adhesive electrodes is not recommended