Abstract
Background:
Kinetic Oscillation Stimulation (KOS) is a novel and non-invasive neuromodulation method for migraine therapy. Emerging evidence suggests that applying low-frequency intranasal vibrations to the sphenopalatine ganglion (SPG) could be a safe and effective option for migraine treatment.
Case report:
We present a case of a 60-year-old man affected by refractory chronic migraine with a history of failure or progressive ineffectiveness of multiple approved therapies. Given the limited available options, we proposed the patient a 6-week treatment cycle with KOS. After 1 month, monthly migraine days (MMD) dropped from 18 to 7, with significant pain reduction by week 6. However, the benefits were not sustained after discontinuation, requiring a second stimulation cycle after 3 months, which yielded an even faster and more significant response.
Conclusions:
This experience reveals KOS safety and effectiveness for long-term SPG neuromodulation, highlighting the potential of focusing treatment on the trigeminal-autonomic reflex (TAR) as a promising direction to pursue.
Introduction
Migraine is a severe brain condition, listed for its widespread prevalence as one of the most disabling neurological disorders. 1 About 2% of the population suffers from refractory chronic migraine, which is often associated with drug-resistance, high disability, and low quality of life. 2
The trigeminal-autonomic reflex (TAR) and parasympathetic outflow play a significant role in migraine pathophysiology. 3
Kinetic oscillation stimulation (KOS) of the sphenopalatine ganglion (SPG) is a minimally invasive neuromodulation method that regulates the TAR. The SPG stimulation through the mucous membrane of the nasal cavity with low-frequency mechanical vibrations can be effective in both tempering acute pain 4 and reducing the frequency of migraine attacks. 5
Clinical case
We report a case of a 60-year-old man who has suffered from migraine since childhood. His family history is positive for migraine, and his medical history includes only a minor head trauma. Over the years, he has experienced two types of headaches: migraine without aura since childhood and tension-type headache with onset in adulthood. Migraine attacks have always been characterized by unilateral pain with side alternation, localized in the frontotemporal area and lasting for several hours. Headache has pulsating quality, with moderate to severe intensity. He use to exhibit a fairly reduced set of autonomic-trigeminal symptoms, predominantly mild tearing ipsilateral to the side of pain. Triggering factors for migraine include sleep deprivation, alcohol, and traveling. In 2008, the patient was diagnosed with chronic migraine according to current criteria (ICHD-2R). 6
Since 2010, he has been followed by our center and has received multiple treatments with preventive drugs, including topiramate, sodium valproate, propranolol, flunarizine, and amitriptyline at the recommended therapeutic dosage. In most cases, the patient reported only temporary improvement in the frequency and intensity of headaches, which lasted only a few months. The neurological examination resulted normal over different evaluations. In 2011, he underwent a brain MRI for headache worsening, which detected small hyperintense lesions in the subcortical white matter, consistent with non-specific gliosis.
He used to treat acute episodes with triptans and non-steroidal anti-inflammatory drugs (NSAIDs), taking up to five symptomatic drugs for each attack. Consequently, he also met the criteria for medication overuse headache (MOH), 6 for which he underwent several detoxification cycles with intravenous steroids and diazepam.
In 2012, upon the advice of another center, the patient underwent CT-guided C2 dorsal root ganglion radiofrequency ablation, but this intervention did not lead to evident clinical amelioration. In 2014, he was diagnosed with hypertension and treated with candesartan for the additional potential benefit on migraine. In the same year, he started receiving quarterly Onabotulinumtoxin-A according to the PREEMPT injection protocol, resulting in only a slight decrease in the intensity of his attacks.
In March 2016, the patient decided to get a “daith piercing” as an attempt to alleviate migraine. Although there is insufficient evidence to substantiate piercing efficacy, the patient experienced a significant, albeit temporary, reduction in migraine attacks and tension-type headaches.
He did not attend follow-up visits until 2020, when, due to a new worsening of his migraine, he was offered a treatment cycle with a calcitonin gene-related peptide receptor antagonist (erenumab). This additional therapy yielded only modest results (from 20 to 14 MMD), and upon discontinuation of monthly administrations, the frequency of attacks rapidly returned to the pre-treatment level, with an average of 18 MMD. Indomethacin stood out as the most effective and well-tolerated symptomatic treatment, combined with short courses of oral steroids prescribed to treat longer and more disabling attacks.
To relieve the high-disabling migraine, in June 2023, we proposed to the patient the innovative treatment with KOS for compassionate use as an additional complementary approach to conventional therapies for migraine prevention.
According to the protocol previously reported, 5 we proposed a cycle of six treatment sessions with Ozilia™ Migraine at weekly intervals (Figure 1). The patient was requested to keep an accurate diary to record headache and migraine days, any changes in his health state, and concomitant medications he might have used in the time span between two sessions.
Our patient during an active treatment session with KOS.
Before each session and during the follow-up period, the patient was requested to fill in an ad hoc questionnaire with validated clinical scales (BS-11, PPI, BRS-6, SF-MPQ, HADS).
The headache-related disability measures showed a HIT-6 score of 65, a MIDAS score of 63, a headache intensity of 6 out of 10 on an 11-point Box Scale (BS-11), and a score of 4 on 6-point Behavioral Rating Scale (BRS-6) at baseline. The pain was more frequently described as stinging and exhausting, and after the attack subsided, a feeling of tenderness lingered. A total score of less than 8 for each depression and anxiety subscale on the HADS questionnaire denoted no warning signal for these conditions.
The treatment was well tolerated throughout all sessions: catheter insertion was always effortless with no intra- or post-procedural complications (e.g., nasal bleeding) except for a minor discomfort caused by the presence of a foreign body in the nasal cavities during stimulation. Between the first and the second session, the patient reported only one migraine attack, allegedly unrelated to his typical triggering factors.
In the subsequent weeks, the patient reported two attacks during the second, three during the third and one during the fourth week of therapy, amounting to a total of seven MMDs over 4 weeks. The scales related to pain intensity (an average of 4 out of 10 on the BS-11 over the 6 weeks of active treatment) and the effects of pain on patient behavior (with a mean score of 3 on the BRS-6) also improved from V1 to V6 (Figure 2). Only during the third week, possibly for a concomitant upper respiratory tract infection, a higher number of attacks were recorded, with a greater perceived pain. Episodic tension-type headache attacks, which he was able to differentiate from migraine, persisted sporadically.
Combination graphs to display the trend of migraine frequency, medication intake, and pain assessment scale scores for each weekly stimulation session relative to the first and second treatment cycles with KOS. BS-11: 11-point Box Scale; PPI: Present Pain Intensity; BRS-6: 6-point Behavioral Rating Scale; WMD: weekly migraine days; WMI: weekly medication intake.
However, after about 3 months from the end of the treatment, the patient complained of a sudden worsening of his migraine condition. In the preceding 30 days, he recorded 14 MMDs with an intake of more than 15 painkillers. He pointed out 6 out of 10 at BS-11 and 4 at BRS-6, with a total HIT-6 score of 60.
Therefore, considering the excellent clinical outcome achieved during and immediately after the first 6-week cycle and reassured by the excellent safety profile of the procedure, we offered the patient a new treatment round with KOS.
A very pronounced effect was again observed as early as the third session of the second cycle, being the week between the second and third stimulation completely free from migraine attacks. The patient reported a pain intensity milder than usual (3 out of 10 on the BS-11 scale), which often restrained him from taking symptomatic medications.
Discussion
Kinetic Oscillating Stimulation, already successfully used for the treatment of non-allergic rhinitis, 7 has obtained the CE certification for the prophylactic treatment of chronic migraine in adults over 18 years of age. It might work by inducing neuromodulation at the level of the SPG through the mucosa of the nasal cavity.
Exploratory trials testing the efficacy of KOS on migraine patients indicated that this treatment could be a fast-acting remedy for acute migraine pain. 4
In a subgroup analysis of a larger multicenter, randomized clinical trial aiming to investigate the clinical efficacy of KOS for the preventive treatment of chronic migraine, active treatment reduced the number of monthly headache days (MHD) with moderate to severe intensity from baseline to weeks 3–6 of treatment and follow-up period when compared to sham stimulation. 5
Our experience, although limited to a single patient with a multifaceted migraine history, align with this evidence. The best results are those related to the frequency of attacks and medication overuse, with a noteworthy impact also on the perceived pain scales.
However, only little benefit outlasted the conclusion of the primary cycle, compelling the need for supplementary stimulations to restore the improvements achieved during active treatment.
Nonetheless, observations regarding a sustained beneficial effect are limited to the 4 weeks post-treatment. 5 Consequently, the deterioration of migraine at 8 weeks after the completion of the primary cycle is not inconsistent with these findings.
Given the multitude of therapeutic failures, including advanced and highly effective treatments, we can label our patient’s response to KOS as very positive. Nevertheless, we must interpret these results cautiously: when it comes to innovative treatments for migraine, the placebo effect can play a significant role, and psychological factors can influence how a person perceives the effectiveness of treatment. However, the consistent benefit obtained through the second cycle of treatment makes the placebo effect possibly less important.
It is worth noting how a patient with so few autonomic symptoms displayed such a favorable response to a treatment aimed at alleviating the autonomic imbalance. Migraine is an intricate condition and its clinical presentation has the potential to evolve over time. However, the long-term changes in the structure and connections of the migraine brain, contribute to the chronic nature of the disease and acting at an apparently secondary level, such as the autonomic nervous system, could also have beneficial effects on pain sensitivity and frequency of attacks.
To the best of our knowledge, this is the first report of such an extensive treatment with KOS in refractory chronic migraine.
There is limited evidence supporting the effectiveness of KOS in the acute treatment of migraine, and even fewer studies (none published so far) explore its use in a chronic setting. With no precise data regarding the ideal duration of a treatment cycle and the persistence of potential beneficial effects, seeking to prolong observations over a more extended period, compared to previous studies, is crucial for advancing this research path.
Conclusion
The preliminary results confirm that KOS treatment is effective both in relieving acute pain and reducing attack frequency. 4,5 Although the precise mechanism by which KOS modulates the TAR is still speculative, it could be a viable alternative to the treatment of resistant or refractory chronic migraine, when other approved treatments have been shown to be ineffective or poorly tolerated. However, there are lingering doubts about its widespread utilization, given the unsuitability of the stimulation device for self-management.
Conclusively, KOS effectiveness needs to be further demonstrated in controlled clinical trials, and indications and limits of applicability must be defined, potentially including other form of primary headaches with notable autonomic activation.
Article highlights
Kinetic oscillation stimulation (KOS) is a novel and drug-free treatment that may be an option for chronic migraine.
KOS administered for 6 weeks on a weekly basis proved to be successful in reducing both the frequency and severity of attacks in a patient with refractory chronic migraine.
While the benefits of KOS did not significantly outlast the active treatment, a second stimulation cycle resulted in an even faster and more remarkable response.
Long-term neuromodulation with KOS could be a viable safe alternative in refractory and complex patients.
Footnotes
Acknowledgments
The authors thank the patient for his consent to use his data for publication and for his input to the manuscript.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical statement
Written informed consent was obtained from the patient for the publication of this case report.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Informed consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.