Starling, Amaal J.

Abstract Background: There is a need for effective and affordable nondrug therapies for the acute treatment of migraine. Transnasal neuromodulation via evaporative cooling may modulate the sphenopalatine ganglion, which is implicated in migraine. The study aimed to evaluate the safety, tolerability, and optimal dose of this method for acute migraine treatment. Methods: A prospective, randomized, double-blind, multicenter study was conducted at 3 US sites. Subjects received 15 minutes of in-clinic treatment during a migraine attack. Twenty-four subjects were randomized into three groups: 24 liters per minute (LPM), 18 LPM, and 6 LPM. Pain and Most Bothersome Symptom (MBS) were recorded at baseline 2 and 24 hours post treatment. The primary endpoint was pain relief (PR) at 2 hours. Secondaryendpoints included tolerability, MBS relief and pain freedom (PF) at 2 hours and 24 hours Results: Eighty-seven adults with episodic migraine with or without aura were enrolled. PR at 2 hours without rescue medication (woRM) was reported by 89% (8/9) of the participants who received 6LPM. PR at 2 hwoRM was reported to be 56% (5/9) and 50% (3/6) in the 18LPM and 24LPM groups, respectively. PF at 2 hours woRM was reported by 44% (4/9) of participants in the 6LPM group, and no participants in the 18LPM or 24LPM group reported PF at 2 hours. MBS relief at 2 hwas 78% (7/9), 67% (6/9) and 50% (3/6) in the 16, 18 & 24LPM groups, respectively. No adverse events occurred in the 6LPM group,and none were serious or severe in any group. Moderate discomfort was reported by 11% (1/9) of the participants in the 6LPM group. In contrast, 33% (3/9) and 83% ofthe 18LPM and 24LPM groups reported moderate or severe discomfort, respectively. Zero, one, and two subjects discontinued the 15-minute session in the 6LPM, 18LPM, and 24LPM groups, respectively. The study was terminated early because of slow subject accrual. Conclusions: Lower flow rates during transnasal cooling were both effective and tolerable for acute migraine treatment. The study became a dose-ranging trial, with lower flow rates,showing greater efficacy. A future at-home study is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT04936061; Registration date: June 15, 2021. The full study protocol can be accessed at https://clinicaltrials.gov/study/NCT04936061.

Abstract Background Slower speaking rates and higher pause rates are found in individuals with migraine or post‐traumatic headache during headache compared to when headache‐free. We aimed to determine whether headache intensity influences the speaking rate and pause rate of participants with migraine or acute post‐traumatic headache (aPTH) following mild traumatic brain injury (mTBI). Methods Using a speech elicitation tool, participants with migraine, aPTH, and healthy controls (HC) submitted speech samples over a period of 3 months. Speaking and pause rates were calculated when participants were headache‐free and when they had mild or moderate headache. In this observational study, speaking and pause rates in participants with migraine and aPTH were compared to HC, controlling for age, sex, and days since mTBI (participants with aPTH only). Results A total of 2902 longitudinal speech samples from 13 individuals with migraine (mean age = 33.5, SD = 6.6; 12 females/1 male), 43 individuals with aPTH (mean age = 44.4, SD = 13.5; 28 females/15 males), and 56 HC (mean age = 40.8, SD = 13.0; 36 females/20 males) were collected. There was no difference in speaking rate between HC and the combined headache cohort of participants (migraine and aPTH) when they had headache freedom or a mild headache. When participants had moderate intensity headache, their speaking rate was significantly slower compared to that of HC and compared to their speaking rate during mild headache intensity or headache freedom. For the combined headache cohort of participants, pause rates were significantly higher when they had headache freedom or had a headache of mild or moderate intensity relative to HC. Compared to participants' pause rate during headache freedom, their pause rate was significantly higher during mild and moderate headache intensity. Participants with aPTH had significantly slower speaking rates compared to participants with migraine during headache freedom, mild headache intensity, and moderate headache intensity. Participants with aPTH had significantly higher pause rates compared to participants with migraine when experiencing moderate headache intensity. Discussion For both aPTH and migraine, more severe headache pain was associated with higher pause rates and slower speaking rates, suggesting that speaking rate and pause rate could serve as objective biomarkers for headache‐related pain. Slower speaking rate in participants with aPTH could reflect additional consequences of TBI‐related effects on motor control and speech production.

Tools used for the identification, evaluation, and monitoring of concussion have not been sufficiently studied in youth or real-world settings. Normative and reliability data on sideline concussion assessment measures in the youth athlete population is needed. Pre-season normative data for 515 athletes (93.5% male) aged 5 to 16 on the Standardized Assessment of Concussion (SAC/SAC-Child), modified Balance Errors Scoring System (mBESS), Timed Tandem Gait (TTG), and the King–Devick Test (KDT) are provided. A total of 212 non-injured athletes repeated the measures post-season to assess test–retest reliability. Mean performance on the SAC-C, mBESS, TTG, and KDT tended to improve with age. KDT was the only measure that demonstrated good to excellent stability across age ranges (ICC = 0.758 to 0.941). Concentration was the only SAC/SAC-C subtest to demonstrate moderate test–retest stability (ICC = 0.503 to 0.706). TTG demonstrated moderate to good (ICC = 0.666 to 0.811) reliability. mBESS demonstrated poor to moderate reliability (ICC = −0.309 to 0.651). Commonly used measures of concussion vary regarding test–retest reliability in youth. The data support the use of at least annual sport concussion baseline assessments in the pediatric population to account for the evolution in performance as the child ages. Understanding the variation in the stability and the evolution of baseline performance will enable improved identification of possible injury.

Abstract Objective To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. Background Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. Methods A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16‐month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age‐ and sex‐matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. Results In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0–3.2]; p = 0.338). Conclusions In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.