[Non-invasive neurostimulation in migraine]. / Neinvazivnaya neirostimulyatsiya pri migreni.

Migraine is the most common chronic neurological disease. Migraine is in the top 5 causes that reduce the quality of life. In recent years, neuromodulation techniques are successfully used with primary headaches. Several variants of non-invasive neuromodulation have been shown to be effective in various forms of migraine. This review analyzes clinical trials and case reports of the effectiveness and safety of non-invasive stimulation of the first branch of the trigeminal nerve in migraine.

Rationale for electrical parameter determination in external trigeminal nerve stimulation (eTNS) for migraine: A narrative review.

BACKGROUND: Migraine is a primary headache disorder involving dysregulation of central and peripheral pain pathways. Medical treatment is often limited by drug side effects, comorbidities and poor compliance. This makes neuromodulation an ideal option for migraine treatment. Cefaly® is a transcutaneous electrical neurostimulator designed specifically for migraine treatment. It results in external trigeminal nerve stimulation of the supraorbital and supratrochlear nerves. External trigeminal nerve stimulation is effective for acute and preventive migraine treatment and may result in normalization of dysregulated pain pathways. OBJECTIVE: Our objective was to provide a narrative review of the neuroanatomical and pathophysiological basis of external trigeminal nerve stimulation for migraine treatment and to provide the rationale behind the choice of the electrical parameters used for external trigeminal nerve stimulation. METHODS: We reviewed external trigeminal nerve stimulation clinical trial publications, basic science neurostimulation literature, publications describing pathophysiological mechanisms in migraine, and documentation used in the application for the Food and Drug Administration approval of external trigeminal nerve stimulation. RESULTS: The electrical parameters used for external trigeminal nerve stimulation were chosen to maximize safety and efficacy. Critical parameters include generator characteristics, pulse shape, pulse duration, pulse frequency and session duration and frequency. We explain the rationale behind determination of each parameter. There is evidence of dysregulated central and peripheral pathways in migraine and evidence that external trigeminal nerve stimulation may normalize function of these pathways. CONCLUSION: External trigeminal nerve stimulation is a safe and effective Food and Drug Administration-approved option for the acute and preventive treatment of migraine. The electrical parameters were optimized specifically for external stimulation of the trigeminal nerve to maximum safety, comfort and efficacy.

Functional Changes of the Perigenual Part of the Anterior Cingulate Cortex after External Trigeminal Neurostimulation in Migraine Patients.

OBJECTIVE: To explore the functional reorganization of the pain processing network during trigeminal heat stimulation (THS) after 60 days of external trigeminal neurostimulation (eTNS) in migraine without aura (MwoA) patients between attacks. METHODS: Using whole-brain BOLD-fMRI, functional response to THS at two different intensities (41 and 51°C) was investigated interictally in 16 adults MwoA patients before and after eTNS with the Cefaly® device. We calculated the percentage of patients having at least a 50% reduction of monthly migraine attacks and migraine days between baseline and the last month of eTNS. Secondary analyses evaluated associations between BOLD signal changes and clinical features of migraine. RESULTS: Before eTNS treatment, there was no difference in BOLD response between MwoA patients and healthy controls (HC) during low-innocuous THS at 41°C, whereas the perigenual part of the right anterior cingulate cortex (ACC) revealed a greater BOLD response to noxious THS at 51°C in MwoA patients when compared to HC. The same area demonstrated a significant reduced BOLD response induced by the noxious THS in MwoA patients after eTNS (p = 0.008). Correlation analyses showed a significant positive correlation between ACC BOLD response to noxious THS before eTNS treatment and the decrease of ACC BOLD response to noxious THS after eTNS. Moreover, a significant negative correlation in the migraine group after eTNS treatment between ACC functional activity changes and both the perceived pain ratings during noxious THS and pre-treatment migraine attack frequency has been found. CONCLUSION: Our findings suggest that eTNS treatment with the Cefaly® device induces a functional antinociceptive modulation in the ACC that is involved in the mechanisms underlying its preventive anti-migraine efficacy. Nevertheless, further observations to confirm whether the observed fMRI effects of eTNS are both related to clinical improvement and specific to antinociceptive modulation in migraine patients are mandatory.

Non-Invasive Neuromodulation for Headache Disorders.

Migraine and other chronic headache disorders are common and if inadequately treated, can lead to significant disability. The effectiveness of medications can be limited by side effects, drug interactions, and comorbid diseases necessitating alternative methods. Technological developments in the past 5 years have made it possible to use non-invasive methods of neuromodulation to treat primary headache disorders. This field includes technologies such as supraorbital transcutaneous stimulation (STS), transcranial magnetic stimulation (TMS), and non-invasive vagal nerve stimulation (nVNS). Existing trials show these modalities are safe and well tolerated and can be combined with standard pharmacotherapy. We review the technologies, biological rationales, and trials involving non-invasive neuromodulation for the treatment of primary headache disorders.

Transcutaneous Supraorbital Nerve Stimulation (t-SNS) with the Cefaly® Device for Migraine Prevention: A Review of the Available Data.

So far, among the different non-invasive neurostimulation methods, only transcutaneous supraorbital nerve stimulation (t-SNS) with the Cefaly® (Cefaly Technology sprl, Herstal, Belgium) device has randomized controlled trial-based evidence for safety and efficacy and obtained American Food and Drug Administration approval for the prevention of episodic migraine. In a double-blinded, randomized, sham-controlled trial on 67 episodic migraine patients (mean pre-treatment migraine days/month: 6.9), the 50% responder rate after 3 months was significantly higher in the active group (38.2%) than in the sham group (12.1%); attack frequency and total headache days were also significantly reduced, but not headache severity. Acute anti-migraine drug intake was reduced by 36.7% in the active group. Statistical sub-analysis suggested that t-SNS was more effective in patients with a higher attack frequency. In a large survey on 2313 Cefaly users about safety and satisfaction only 4.3% of subjects reported side effects, all of which were minor and fully reversible, the most frequent being intolerance to the paresthesia feeling and the most severe an allergic skin reaction to the electrode gel. The efficacy/safety ratio of the Cefaly device was therefore most favorable, especially when compared to preventive anti-migraine drugs. The therapeutic efficacy of t-SNS with Cefaly with low-frequency migraine (≤5 attacks/month) was recently confirmed in an open randomized trial. No published data are available in chronic migraine. According to preliminary results of a fluorodeoxyglucose-positron emission tomography study, Cefaly might exert its effect in migraine by increasing activity in crucial areas of the limbic system and salience matrix such as orbitofrontal and anterior cingulate cortices.