Clinical Experience With Transcutaneous Supraorbital Nerve Stimulation in Refractory Migraine
Clinical Experience With Transcutaneous Supraorbital Nerve Stimulation in Refractory Migraine
Migraine is included in the top-ten disabling diseases and conditions among the Western
 populations. Non-invasive neurostimulation (t-SMS), including the Cefaly® device, for the
 treatment of various types of pain is a relatively new field of interest. The aim of the
 present study was to explore the clinical experience with Cefaly® in a cohort of migraine
 patients previously refractory or non-tolerant to topiramate prophylaxis.

 Patients were followed prospectively after having been diagnosed with episodic or chronic
 migraine with a previous failure to topiramate treatment and having consented to receive
 preventive treatment with Cefaly® according to their treating physician's suggestion. A
 1-month period of baseline observation was followed by a 3-month period of active treatment
 with transcutaneous supraorbital nerve stimulation (t-SNS) with Cefaly® as the only
 preventive treatment.
Migraine is ranked as the sixth most disabling condition, worldwide.Presently, medications
 are the mainstream of migraine management; however, preventive treatment is often far from
 optimal. Preventive treatment for migraine is usually considered when migraine pain is
 present more frequently than twice a week.

 Topiramate is currently the most commonly used first-line approved preventive medication for
 migraine. With this being said, not all patients respond to preventive medications, due to
 either lack of efficacy or to adverse events. As a matter of fact, adherence to migraine
 preventive medications, including topiramate, may be insufficient. In a health insurance
 database based review, 70.2% of patients who initiated migraine prophylaxis with
 antiepileptics were reported to be non-adherent after 6 months. Among preventive medication
 choices, patients are reported to adhere best, but not optimally to topiramate, with adverse
 events being the most common reason for topiramate discontinuation.

 On the other hand, non-invasive neurostimulation is a relatively new field of interest for
 the treatment of various types of pain. Clinical research in this field is active, as the
 recent technological advances allow for safe, convenient and ease by which to self-administer
 treatment sessions. Cefaly® electrically the supraorbital nerve in the forehead. The
 supraorbital nerve is a branch of the first trigeminal division. The trigeminovascular system
 has a well-known involvement in headache pain. Transcutaneous supraorbital nerve stimulation
 (t-SNS) with the Cefaly® (Cefaly® Technology sprl, Herstal, Belgium) device has proved to be
 a safe and efficient method for convenient self-delivered treatment sessions. It has received
 approval for the prevention of episodic migraine by the American Food and Drug Administration
 and by the EU, including Greece, since early 2015.

 Although t-SNS use is spreading in Greece, it is not reimbursed by the social security system
 and in many cases it may be postponed until either a first line preventive medication fails
 to provide substantial relief or tolerability / safety issues ensue.

 The aim of the present study was to explore and share the clinical experience with Cefaly® in
 a cohort of migraine patients previously refractory or intolerant to preventive treatment
 with topiramate, as this is a common situation in clinical practice. Additionally, we
 specifically explored whether the reason for the discontinuation of topiramate is correlated
 with the outcome of Cefaly® treatment. To the best of the authors' knowledge, no similar
 study has been published so far.

 METHODS This was an exploratory prospective multicenter clinical study conducted in
 accordance with the principles of the Helsinki Declaration and approved by the principal
 investigator's (MV) Institutional Review Board. This study was done to explore the efficiency
 and safety of Cefaly® in migraine prevention in a population of patients previously
 refractory or intolerant to topiramate.

 Participants to be treated with Cefaly® were enrolled from 2 private headache clinics,
 located in Athens and Thessaloniki, the first and second largest cities of Greece,
 respectively. Patients were diagnosed with episodic or chronic migraine, needed preventive
 treatment according to the treating physician's opinion, and they had not responded to
 previous topiramate treatment, either due to inefficacy or due to intolerability or safety
 issues. In order to consider topiramate as failed due to inefficacy, a dose of 100mg/day for
 at least 3 months was required to have been received. Topiramate was considered as failed due
 to intolerability in any case a patient had decided to stop use of topiramate due to an
 adverse event regardless of its nature or severity. Patients had to have stopped topiramate
 at least 3 months prior to starting treatment with Cefaly®.

 Both episodic and chronic (≥ 15 days of headache per month) migraine patients, according to
 the International Classification of Headache Disorders 3rd edition-beta version (ICHD IIIβ),
 were included. Upon enrolment and after giving consent to participate in the study,
 demographics and clinical data were captured, including the reason for topiramate
 discontinuation. Patients were then provided with a headache (HA) diary to be self-completed
 over the course of the study including questions about occurrence of HA, peak intensity level
 on a 0-10 numerical scale, number of acute medication doses and any adverse event. A 1-month
 baseline observation period was followed by a 3-month active treatment period with Cefaly® as
 the only preventive treatment. During the active treatment period, compliance (days the
 device was used as recommended, e.g. 1 full session each day) was also recorded.

 The European version of Cefaly® includes three stimulation programs; one for acute migraine
 relief and two programs to be implemented in daily 20-minute sessions, one for migraine
 prevention and one for relaxation. In our study, Cefaly® was to be used based upon the
 protocol of the approval study of the device, in which it is used once every day on the
 migraine prevention program.

 At their last evaluation, patients answered two additional questions regarding their total
 subjective satisfaction from treatment with t-SNS. The first question ("Are you satisfied
 with Cefaly® and wish to continue the treatment?") was aimed to access overall satisfaction
 from t-SNS treatment and the will to continue treatment, which was the primary evaluation of
 our study. The second question ("Did you encounter technical issues with the device?") was
 aimed to access any problems or technical difficulties arising from the use of the device.

 Changes in total headache days, number of HA days with intensity ≥5/10 and days with acute
 medication use were analysed from baseline to the last observation or Month-3 of active
 treatment.
Inclusion Criteria:

 - Migraine according to the criteria of International Headache Society classification III
 lack of response or intolerance to topiramate. Patient's consent

 Exclusion Criteria:

 - No