External Trigeminal Nerve Stimulation Research Articles

The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS)

BackgroundAttention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action.MethodsA confirmatory, sham-controlled, double-blind, parallel-arm, multi-centre phase IIb RCT of 4 weeks of eTNS in 150 youth with ADHD, recruited in London, Portsmouth, and Southampton, UK. Youth with ADHD will be randomized to either real or sham eTNS, applied nightly for 4 weeks. Primary outcome is the change in the investigator-administered parent rated ADHD rating scale. Secondary outcomes are other clinical and cognitive measures, objective hyperactivity and pupillometry measures, side effects, and maintenance of effects over 6 months. The mechanisms of action will be tested in a subgroup of 56 participants using magnetic resonance imaging (MRI) before and after the 4-week treatment.DiscussionThis multi-centre phase IIb RCT will confirm whether eTNS is effective in a larger age range of children and adolescents with ADHD, whether it improves cognition and other clinical measures, whether efficacy persists at 6 months and it will test underlying brain mechanisms. The results will establish whether eTNS is effective and safe as a novel non-pharmacological treatment for ADHD.Trial registration: ISRCTN82129325 on 02/08/2021, https://doi.org/10.1186/ISRCTN82129325.

An update on migraine: Current and new treatment options.

Migraine headache is a common and potentially debilitating disorder often treated by physician associates/assistants (PAs) and other providers. With the recent advances in new drugs and device technology for the treatment of migraine, the American Headache Society has released a consensus statement on both preventive and acute strategies for clinical practice. The US FDA has recently approved various types of medications and devices for the treatment and prevention of migraine attacks including several calcitonin gene-related peptide (CGRP) receptor inhibitors, a selective serotonin receptor agonist (SSRA), noninvasive vagus nerve stimulation (nVNS), external trigeminal nerve stimulation (e-TNS), and external concurrent occipital and trigeminal neurostimulation (eCOT-NS), among other pharmacologic and nonpharmacologic options. This article provides a review of migraine prevention and acute treatment protocol, highlighting new approaches to both.

30.2 Network Connectivity Changes Underlying Responses to Trigeminal Nerve Stimulation in ADHD: RCT Results

External trigeminal nerve stimulation (TNS) is a noninvasive method of brain modulation that received FDA device clearance in 2019 for treatment of children aged 7 to 12 years with ADHD. Children randomized to active TNS exhibited significantly greater improvements in ADHD symptoms (p < .005) than sham and increased EEG power in the right frontal (F4) and frontal midline (Fz) brain regions. This presentation examines changes in resting-state functional connectivity to more fully characterize the neural mechanisms underlying TNS treatment–related improvements in ADHD.

Outpatient Approach to Resistant and Refractory Migraine in Children and Adolescents: a Narrative Review.

Migraine is one of the top reasons for consulting a pediatric neurologist. Although the majority of children and adolescents who receive evidence-based first-line interventions for migraine will improve substantially, a subset of patients develop resistant or refractory migraine. In this review, we summarize the level of evidence for a variety of acute and preventive treatment options to consider in children and adolescents with resistant or refractory migraine. We describe the level of evidence for interventional procedures (onabotulinumtoxinA injections, greater occipital and other nerve blocks), neuromodulation (single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, remote electrical neuromodulation, and non-invasive vagal nerve stimulation), calcitonin gene-related peptide (CGRP) pathway antagonists (anti-CGRP monoclonal antibodies and gepants), psychological therapies, and manual therapies (acupuncture, craniosacral therapy, massage and physical therapy, and spinal manipulation).

Neurotherapeutics for ADHD: Do they work?

This paper reflects on the use of neurotherapeutics for attention-deficit/hyperactivity disorder (ADHD). ADHD is the most imaged child psychiatric disorder, with over 3 decades of magnetic resonance imaging (MRI) research. Findings are relatively homogeneous compared to other psychiatric conditions with consistent evidence for differences, albeit small, relative to healthy controls in the structure and function of several frontal, parietotemporal, and striatal brain regions as well as their inter-regional structural and functional connections. The functional deficits have been targeted with modern neurotherapeutics, including neurofeedback (using most commonly electroencephalography and more recently functional near-infrared spectroscopy and functional MRI) and non-invasive brain stimulation (such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation, or external trigeminal nerve stimulation). Except for electroencephalography-neurofeedback, the majority of neurotherapeutic studies have been relatively small, with very heterogenous research protocols and outcome measures and-likely as a consequence-inconsistent findings. Furthermore, most brain stimulation studies have tested effects on cognitive functions rather than clinical symptoms. So far, findings have not been very promising. Future studies require systematic testing of optimal protocols in large samples or homogenous subgroups to understand response prediction that could lead to individualized treatment.

Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM)

Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2–8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting.Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904.

External Trigeminal Nerve Stimulation as a Non-pharmacological Option for the Prevention and Acute Treatment of Migraine

Migraine is a common condition affecting approximately 1.04 billion people worldwide. Despite the available pharmaceutical therapies, patients with migraine often prefer, or may require, non-medicinal treatments for their disease. External trigeminal nerve stimulation (e-TNS) is a non-invasive, non-drug device treatment approved by the US Food and Drug Administration for the prevention and acute treatment of migraine. The trigeminovascular system plays a key role in migraine pathophysiology; e-TNS percutaneously stimulates the supraorbital and supratrochlear branches of the ophthalmic division of the trigeminal nerve. This article reviews published studies of e-TNS in the prevention and acute treatment of migraine, highlights the versatility of e-TNS in individualizing migraine treatment and discusses future directions for research and clinical applications of e-TNS therapy.

Non-invasive neuromodulation in the acute treatment of migraine: a systematic review and meta-analysis of randomized controlled trials.

A systematic review and meta-analysis was performed to determine the efficacy of non-invasive neuromodulation modalities for the treatment of acute migraine. Although pharmacological treatments are the gold standard for the management of acute migraine, some patients may require non-pharmacological treatment options. Non-invasive neuromodulation may provide an alternative, and techniques include transcranial magnetic stimulation (TMS), non-invasive vagal nerve stimulation (nVNS), non-painful remote electrical stimulation (NRES), and external trigeminal nerve stimulation (e-TNS). This systematic review and meta-analysis was performed following PRISMA guidelines. We searched PUBMED, EMBASE, ClinicalTrials.gov, Cochrane Center Register of Controlled Trials, and LILACS databases. We included randomized controlled clinical trials studying patients with migraine treated with any form of non-invasive neuromodulation. Primary outcome was pain freedom within 2h post-treatment. Secondary outcomes were pain relief within 2-h post-treatment and sustained pain freedom and sustained pain relief 48h post-treatment. Pooled analysis demonstrated a significant effect of non-invasive neuromodulation on pain-free rates within 2h (RR, 1.66; 95% CI, 1.35 to 2.05; P < 0.00001) and pain relief rates within 2h (RR, 1.52; 95% CI, 1.13 to 2.05; P = 0.005) post-treatment. Non-invasive neuromodulation had no significant effect on sustained pain freedom at 48h (RR, 1.56; 95% CI, 0.68 to 3.59; P = 0.29) or sustained pain relief at 48h (RR, 1.47; 95% CI, 0.57 to 3.77; P = 0.43) after administration. Neuromodulation has demonstrated some efficacy in acute migraine management and may be considered in the treatment paradigm of acute migraine in patients with contraindications to pharmacological therapies.

Acute Treatments for Episodic Migraine in Adults

Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy. To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults. Multiple databases from database inception to February 24, 2021. Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks. Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small. The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham. There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.

Preventive Migraine Treatment.

This article provides an overview of preventive interventions for migraine, including when to start and how to choose a treatment, pharmacologic options (both older oral treatments and new monoclonal antibodies to calcitonin gene-related peptide [CGRP] or its receptor), nonpharmacologic treatment such as neuromodulation, and preventive treatment of refractory migraine. The migraine preventive treatment landscape has been transformed by the development of monoclonal antibodies targeting CGRP or its receptor. These treatments, which are given subcutaneously or intravenously monthly or quarterly, have high efficacy and were well tolerated in clinical trials. Emerging real-world studies have found higher rates of adverse events than were seen in clinical trials. They are currently recommended for use if two traditional preventive therapies have proven inadequate. Since the commonly cited 2012 American Headache Society/American Academy of Neurology migraine prevention guidelines were released, clinical trials supporting the preventive use of lisinopril, candesartan, and memantine have been published. Neuromodulation devices, including external trigeminal nerve stimulation and single-pulse transcranial magnetic stimulation devices, have modest evidence to support preventive use. The American Headache Society/American Academy of Neurology guidelines for the preventive treatment of migraine are currently being updated. A new class of oral CGRP receptor antagonists (gepants) is being tested for migraine prevention. Successful preventive treatment of migraine reduces disease burden and improves quality of life. Many pharmacologic and nonpharmacologic treatment options are available for the prevention of migraine, including newer therapies aimed at the CGRP pathway as well as older treatments with good evidence for efficacy. Multiple treatment trials may be required to find the best preventive for an individual patient.

Interventional Treatments Expand Psychiatrists’ Treatment Options

Interventional Treatments Expand Psychiatrists’ Treatment Options

Non-Invasive Neuromodulation for the Treatment of Migraine and Cluster Headache

Migraine and cluster headache are common headache disorders that impact patients' quality of life. The pharmacotherapy for acute headache attacks is sometimes ineffective, and the adherence to preventive medications is low due to their side effects and/or lack of efficacy. Recently, several non-invasive neuromodulation devices for primary headache disorders have been launched and attracted the attention of patients and physicians because of their practicality, safety, and the possibility of becoming new treatment options. In this review, we describe external trigeminal nerve stimulation (eTNS), non-invasive vagal nerve stimulation (nVNS), and single-pulse transcranial magnetic stimulation (sTMS) which have been well studied in recent randomized sham-controlled trials and open-label studies. We also describe their mechanisms of action and adverse events.

Влияние неинвазивной нейростимуляции тройничного нерва на коррекцию вестибулярного компонента у пациентов с вестибулярной мигренью

Aim: to study the possibilities of vestibular component correction in patients with vestibular migraine using external trigeminal nerve stimulation. Patients and Methods: the study included 42 patients (32 of them women) aged 18 to 50 y.o., with established vestibular migraine. All patients underwent external trigeminal nerve stimulation. The duration of each therapeutic course was 20 minutes, the frequency was 3 times a week for 3 months. The assessment of the condition dynamics was conducted using the Dizziness Handicap Inventory (DHI), Subjective Vestibular Assessment on a 5-point scale and Vestibular Rehabilitation Benefit Questionnaire. Results: at the first visit, the majority (77%) of patients suffered from severe dizziness, 23% of patients experienced moderate symptoms. After treatment, most patients experienced only mild symptoms of dizziness, while 31% of patients had no symptoms of dizziness. The total score for DHI before treatment was 58 (95% CI 54–63), after treatment — 19 (95% CI 16–24) (p&lt;0,05). The median indicator of life quality deficiency according to the Vestibular Rehabilitation Benefit Questionnaire before correction of vestibular dysfunction was 57 (95% CI 51.3–64.8), after external stimulation course — 38 (95% CI 32.7–44.6) (p&lt;0.05). Conclusion: external trigeminal nerve stimulation can be considered as an actual non-pharmacological method of vestibular dysfunction correction in patients with vestibular migraine. KEYWORDS: vestibular dysfunction, dizziness, vestibular migraine, external trigeminal nerve stimulation, life quality. FOR CITATION: Illarionova E.M., Gribova N.P. The effect of external trigeminal nerve stimulation on the vestibular component correction in patients with vestibular migraine. Russian Medical Inquiry. 2021;5(10):683–686 (in Russ.). DOI: 10.32364/2587-6821-2021-5-10-683-686.

Peripheral Neuromodulation for the Management of Headache.

ContextNeuromodulation is an expanding field of study for headache treatment to reduce pain by targeting structures within the nervous system that are commonly involved in headache pathophysiology, such as the vagus nerve (VNS), occipital nerves, or sphenopalatine ganglion (SPG) for stimulation. Pharmaceutical medical therapies for abortive and prophylactic treatment, such as triptans, NSAIDs, beta-blockers, TCAs, and antiepileptics, are effective for some individuals, but the role that technology plays in investigating other therapeutic modalities is essential. Peripheral neuromodulation has gained popularity and FDA approval for use in treating certain headaches and migraine headache conditions, particularly in those who are refractory to treatment. Early trials found FDA approved neurostimulatory implant devices, including Cephaly and SpringTMS, improved patient-oriented outcomes with reductions in headaches per month (frequency) and severity.Evidence AcquisitionThis was a narrative review. The sources for this review are as follows: Searching on PubMed, Google Scholar, Medline, and ScienceDirect from 1990 - 2019 using keywords: Peripheral Neuromodulation, Headache, vagus nerve, occipital nerves, sphenopalatine ganglion.ResultsThe first noninvasive neurostimulator device approved for migraine treatment was the Cefaly device, an external trigeminal nerve stimulation device (e-TNS) that transcutaneously excites the supratrochlear and supraorbital branches of the ophthalmic nerve. The second noninvasive neurostimulation device receiving FDA approval was the single-pulse transcranial magnetic stimulator, SpringTMS, positioned at the occiput to treat migraine with aura. GammaCore is a handheld transcutaneous vagal nerve stimulator applied directly to the neck at home by the patient for treatment of cluster headache (CH) and migraine. Several other devices are in development for the treatment of headaches and target headache evolution at different levels and inputs. The Scion device is a caloric vestibular stimulator (CVS) which interfaces with the user through a set of small cones resting in the ear canal on either side and held in place by modified over-ear headphones. The pulsante SPG Microstimulator is a patient-controlled device implanted in the patient’s upper jaw via an hour-long oral procedure to target the sphenopalatine ganglion. The occipital nerve stimulator (ONS) is an invasive neuromodulation device for headache treatment that consists of an implanted pulse generator on the chest wall connected to a subcutaneous lead with 4 - 8 electrodes that is tunneled the occiput.ConclusionsThe aim of this review is to provide a comprehensive overview of the efficacy, preliminary outcomes, and limitations of neurostimulatory implants available for use in the US and those pending further development.

Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder: Cognitive and Electroencephalographic Predictors of Treatment Response

The current study applies a precision medicine approach to trigeminal nerve simulation (TNS), a Food and Drug Administration-approved neuromodulation treatment for attention-deficit/hyperactivity disorder (ADHD), by testing secondary outcomes of cognitive and electroencephalographic [EEG] predictors of treatment response among subjects from the original randomized controlled trial. Children aged 8 to 12 years with ADHD, were randomized to 4 weeks of active or sham TNS treatment, after which the sham group crossed over into 4 weeks of open-label treatment. TNS treatment responders (RESP) had an ADHD Rating Scale (ADHD-RS) Total score reduction of≥25%, whereas nonresponders (NR) had<25% reduction posttreatment. Assessments included weekly behavioral ratings and pre-/posttreatment cognitive EEG measures. The final sample was 25 RESP and 26 NR comprising 34 male and 17 female children, with a mean (SD) age of 10.3 (1.4) years. Baseline measures that significantly differentiated RESP from NR included: lower working memory, lower spelling and mathematics achievement, deficits on behavioral ratings of executive function (BRIEF), and lower resting state EEG power in the right frontal (F4) region (all p values<.05). Compared to NRs, responders showed significantly increased right frontal EEG power with TNS treatment, which was predictive of improved executive functions and ADHD symptomatology (β= 0.65, p< .001). When EEG findings and behavior were modeled together, the area under the curve (AUC) for BRIEF Working Memory scale was 0.83 (p= .003), indicating moderate prediction of treatment response. Children with ADHD who have executive dysfunction are more likely to be TNS responders and show modulation of right frontal brain activity, improved/normalized executive functions, and ADHD symptom reduction. Developmental Pilot Study of External Trigeminal Nerve Stimulation for ADHD; http://clinicaltrials.gov; NCT02155608.

External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial

BackgroundExternal trigeminal nerve stimulation (ETNS) is an emergent, non-invasive neurostimulation therapy delivered bilaterally with adhesive skin electrodes. In previous studies, ETNS was associated to a decrease in seizure frequency in patients with focal drug-resistant epilepsy (DRE). ObjectiveTo determine the long-term efficacy and tolerability of ETNS in patients with focal DRE. Moreover, to explore whether its efficacy depends on the epileptogenic zone (frontal or temporal), and its impact on mood, cognitive function, quality of life, and trigeminal nerve excitability. MethodsForty consecutive patients with frontal or temporal DRE, unsuitable for surgery, were randomized to ETNS or usual medical treatment. Participants were evaluated at 3, 6 and 12 months for efficacy, side effects, mood scales, neuropsychological tests and trigeminal nerve excitability. ResultsSubjects had a median of 15 seizures per month and had tried a median of 12.5 antiepileptic drugs. At 12 months, percentage of responders was 50% in ETNS group and 0% in control group. Seizure frequency in ETNS group decreased by −43.5% from baseline. Temporal epilepsy subgroup responded better than frontal epilepsy subgroup (55.56% vs. 45.45%, respectively). Median stimulation intensity was 6.2 mA. ETNS improved quality of life, but not anxiety or depression. Long-term ETNS affected neither neuropsychological function, nor trigeminal nerve excitability. No relevant adverse events were observed. ConclusionsETNS is an effective and well-tolerated therapy for focal DRE. Patients with temporal epilepsy showed a better response than those with frontal epilepsy. Future studies with larger populations may define its role compared to other neurostimulation techniques. Classification of evidenceThis study provides Class II evidence that ETNS reduces seizure frequency in patients with focal DRE.

External trigeminal nerve stimulation: Potential rescue treatment for acute vestibular migraine

ObjectiveVestibular migraine (VM) is the most common neurologic cause of vertigo among adults. However, there are no specifically studied or approved rescue therapies for acute VM attacks. This study describes how external trigeminal nerve stimulation (eTNS) using the Cefaly® (CEFALY Technology, Seraing, Belgium) device relieves acute VM episodes. MethodsSingle-center, retrospective review of 19 patients with acute VM attacks (seen between May 2018 and June 2019) treated with 20-min eTNS. Prior to treatment, patients graded the severity of their vertigo/headache using a 10-point visual analog scale (VAS) with 0 representing no vertigo/headache, and 10 representing the worst imaginable vertigo/headache. After eTNS, patients graded their vertigo/headache using the same VAS 15 min. In addition, bedside neuro-otologic examination was performed before and after treatment. Results19/19 patients reported improvement in vertigo severity. Mean vertigo severity was 6.6 (±2.1; median 7) before eTNS, and 2.7 (±2.6; median 3) following treatment; mean improvement in vertigo was 61.3% (±32.6; median 50.0%). During VM episodes, 14/19 experienced headache. Mean headache severity was 4.8 (±2.4; median 4.5) before eTNS, and was 1.4 (±2.4; median 0) following treatment; mean improvement in headache was 77.2% (±32.7; median 100.0%). Neuro-otologic examination was normal during VM attacks in all except Patient 7 who had spontaneous upbeat nystagmus which resolved after eTNS. Other improvements include improvement of eye pressure, head pressure, and chronic facial pain. No intolerable side effects were reported. ConclusionThis study provides preliminary evidence that eTNS is a novel, non-invasive, safe and effective treatment for acute VM attacks.

Primary headache disorders: Five new things.

Purpose of reviewTo review 5 new areas in primary headache disorders, especially migraine and cluster headache.Recent findingsCalcitonin gene-related peptide (CGRP) receptor antagonists (gepants—rimegepant and ubrogepant) and serotonin 5-HT1F receptor agonists (ditans—lasmiditan) have completed phase 3 clinical trials and will soon offer novel, effective, well-tolerated nonvasoconstrictor options to treat acute migraine. CGRP preventive treatment is being revolutionized after the licensing of 3 monoclonal antibodies (MABs), erenumab, fremanezumab, and galcanezumab, with eptinezumab to follow, especially designed for migraine; they are effective and well tolerated. For patients seeking a nondrug therapy, neuromodulation approaches, single-pulse transcranial magnetic stimulation, noninvasive vagus nerve stimulation (nVNS), and external trigeminal nerve stimulation, represent licensed, well-tolerated approaches to migraine treatment. For the acute treatment of episodic cluster headache, nVNS is effective, well tolerated, and licensed; nVNS is effective and well tolerated in preventive treatment of cluster headache. The CGRP MAB galcanezumab was effective and well tolerated in a placebo-controlled trial in the preventive treatment of episodic cluster headache. Sphenopalatine ganglion stimulation has been shown to be effective and well tolerated in 2 randomized sham-controlled studies on chronic cluster headache. Understanding the premonitory (prodromal) phase of migraine during which patients experience symptoms such as yawning, tiredness, cognitive dysfunction, and food cravings may help explain apparent migraine triggers in some patients, thus offering better self-management.SummaryHeadache medicine has made remarkable strides, particularly in understanding migraine and cluster headache in the past 5 years. For the most common reason to visit a neurologist, therapeutic advances offer patients reduced disability and neurologists a rewarding, key role in improving the lives of those with migraine and cluster headache.

FDA approves marketing of first nondrug treatment for ADHD

The U.S. Food and Drug Administration (FDA) announced April 19 approval to market the first medical device to treat attention deficit hyperactivity disorder (ADHD). The prescription‐only device, called the Monarch external Trigeminal Nerve Stimulation (eTNS) System, is indicated for patients ages 7 to 12 years old who are not currently taking prescription ADHD medication.

External trigeminal nerve stimulation: A long term follow up study

PurposeExternal trigeminal nerve stimulation is an emerging noninvasive therapy for drug resistant epilepsy (DRE). The aim of this study is to describe the long-term outcome of a series of patients treated with eTNS. MethodsWe present a retrospective observational study of patients with DRE who received eTNS treatment, comparing the monthly seizure frequency during the 3-months period before eTNS initiation with the monthly seizure frequency at 6, 12, 24, 36 and 48 months after eTNS. We analyze the responder rate, the retention rate and the tolerability. Results17 patients with highly drug-resistant epilepsy were included. Mean follow-up was 2194 [6–56] months. The responder rate was 35% at 6 months and 12 months, 23% at 24 months, 19% at 36 months, and 14% at 48 months. Retention rates at the same periods were 88%, 53%, 41%, 37.5% and 28.5%. There were no reports of serious adverse events. Four patients reported improvement in sleep and better mood. ConclusionThe effectivity of eTNS is similar to some of the new treatments available, with a retention rate of 52% in the first year and 285% at 4 years. Tolerability is excellent with only mild effects reported by a minority of patients.