Chaudhary, Hira

Abstract Introduction Restless Legs Syndrome (RLS) affects up to 3% of the adult population in the United States, with approximately one-third of these individuals experiencing medically refractory disease. Historically, treatments for RLS have included iron replacement, dopamine agonists, and alpha-2-delta ligands. However, dopamine agonists are often associated with augmentation, a phenomenon in which RLS symptoms worsen. This includes increased severity, earlier onset, spread of symptoms to other parts of the body, and the need for higher doses of medications. Over the past decade, the use of opioid therapy for refractory RLS has become more widely accepted. Buprenorphine-naloxone, a combination medication, includes buprenorphine, a partial agonist at the mu-opioid receptor, which is less likely to cause respiratory depression, overdose, or euphoria compared to full agonists. Naloxone, an opioid antagonist, is included to deter misuse. Here, we share the treatment responses of three patients with refractory RLS who were treated with buprenorphine-naloxone. Report of case Pre- and post-treatment IRLS were compared in three Sleep Medicine patients (two females, aged 70, and one male, aged 72) on therapeutic doses of buprenorphine-naloxone. Patient charts were reviewed for medication side effects. Previous treatments included dopamine agonists, alpha-2-delta ligands, iron supplementation, benzodiazepines, methadone, and melatonin. Pre-treatment IRLS scores were 13, 13, and 24, classified as moderate to severe. The formulations used included buprenorphine-naloxone 2-0.5 mg sublingual tablets and buprenorphine-naloxone 2-0.5 mg 1/8 films. Therapeutic daily doses of buprenorphine-naloxone ranged from 7.5 to 60 morphine milligram equivalents (MME) per day. Post-treatment IRLS scores were 0, 2, and 3, representing an average reduction of over 15 points on the IRLS. Average time between pre- and post-treatment IRLS was 29 months. Side effects were reported by one patient, including fatigue, depressive symptoms, and reflux, but none of the patients experienced side effects that limited the use of the medication. Conclusion In this case series, we demonstrate the positive impact of buprenorphine-naloxone in managing refractory RLS, as evidenced by substantial reductions in IRLS scores from moderate to severe levels. We hope to encourage clinicians to consider buprenorphine-naloxone as an effective and well-tolerated treatment option for patients with refractory RLS. Support (if any)

Introduction: Previous studies have established the safety and economic benefits of outpatient Transient Ischemic Attack (TIA) management, highlighting reduced expenses for outpatient evaluation. This context underscores the potential advantages of refined outpatient TIA management, a focus of our study, through the implementation of a novel expedited outpatient TIA workflow and assessment of its economic, administrative and clinical impact. Methods: We implemented a novel TIA pathway including streamlined assessments by emergency department (ED) physicians, a structured expedited set of diagnostic tests and outpatient follow-up with vascular neurologists within 48-72 hours of ED presentation. We conducted a retrospective cost-efficacy analysis, contrasting two phases: pre-implementation (standard ED-to-hospital admission TIA workflow from May 1, 2020 - December 31, 2020) and post-implementation (ED-to- outpatient TIA workflow from May 1, 2021 - December 31, 2021). We also compared the clinical outcomes of patients with a final diagnosis of TIA or minor ischemic stroke syndrome from the implementation cohort (May 2021-May 2022) with those from an ABCD2-matched inpatient TIA cohort evaluated in the pre-implementation period (2017-2021). Results: The newly implemented outpatient TIA workflow resulted in a 7% decrease in admissions to hospital observation status, 14.8% reduction in hospital admissions, whereas ED discharge rates rose by 20.4%. Within 8 months, these changes equated to 21 fewer hospitalizations or admissions, reducing costs by approximately $103,320 (Figure1). Laboratories, diagnostic imaging, and neurology evaluations were completed faster in the inpatient pathway. Both pathways had similar vascular risk factors and outcomes regarding final diagnosis, - diagnostic testing achieved, preventative treatments prescribed, stroke/TIA recurrences, re-admissions, TIA-related morbidity and mortality, and related ED return visits (Table 1). Conclusion: The deployment of an optimized outpatient TIA management workflow at Mayo Clinic Arizona had demonstrated improved administrative and cost efficiency, with similar clinical outcomes as inpatient TIA pathway. This investigation corroborates the efficacy of workflow enhancements in outpatient TIA settings and suggests a scalable model for analogous strategies in other medical centers.

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by repetitive airway narrowing or collapse during sleep. Hypoglossal nerve stimulation (HNS) is one alternative therapy. After device implantation and activation, it is patient-titrated based on symptoms. A sleep study then confirms effective settings based on an apnea-hypopnea index (AHI) below 5. Symptomatic control alone may not entail low AHI. Objective data with overnight oximetry during titration may help bridge this. We describe a patient in whom Wellue pulse oximeter was used during self-titration of the Inspire HNS. Report of case(s) A 63 year-old male presented in June 2022 for HNS evaluation due to gasping and witnessed apneas. AutoPAP trial had failed. In November 2022 diagnostic polysomnography revealed an AHI of 18 and lowest oxygen saturation (OS) of 80%. Sleep endoscopy in February 2023 confirmed no concentric collapse at the level of the velum. He underwent HNS implantation in May 2023 and activation in June. Initial sensation and functional thresholds were 0.6 volts. Amplitude range was 0.6 to 1.6 volts, pulse width 90 microseconds, rate 33 hertz, pause time 15 minutes, electrode configuration [+,-,+], and duration 8 hours. In July, he felt 0.7 volts controlled symptoms. A Watchpat home sleep study revealed an AHI of 46.2 and lowest OS of 82%. He purchased a pulse oximeter and was shown the oxygen desaturation index (ODI) at >3%. On increasing to 1.0 volts, oximetry revealed ODI 8.65 averaged over 4 nights. At 1.1 volts, ODI improved to 0.9-4.14. Since ODI was below 5, he had subsequent in-laboratory titration, revealing at 1.1 volts the residual AHI was 2.5. The lowest OS was 89% with a mean of 95%. Conclusion The post-activation procedure for HNS utilizes symptom-based self-titration. Sleep studies may reveal continued apnea despite self-reported symptom control. We suspect overnight oximetry during self-titration may improve efficacy. In this case, after self-titration with oximetry to decide an amplitude setting, home and in-laboratory sleep studies confirmed effective control. This preliminarily suggests that overnight oximetry used with HNS during the self-titration phase may improve titration outcomes as confirmed by formal polysomnography. Support (if any)

Abstract Background Erenumab is a monoclonal antibody that targets the calcitonin gene‐related peptide (CGRP) receptor and is approved for the preventative treatment of migraine in adults. CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension. While there has not been evidence of hypertension in preclinical models or clinical trials, post‐marketing data suggest erenumab may be associated with hypertension. This led to a warning in the United States Food and Drug Administration prescribing information for erenumab. Objective To determine the frequency of worsening blood pressure (BP) after initiation of erenumab in patients with migraine and how this is associated with hypertension. Methods This is an observational retrospective cohort study evaluating patients at a tertiary headache or neurology department. Systolic and diastolic BPs were compared between the initial visit prior to initiation of erenumab, and follow‐up visit while on erenumab. Worsening BP was defined as moving from a lower stage to a higher stage of BP, as defined by the American Heart Association. Serious adverse vascular events were also recorded. Results A total of 335 patients were included in the final analysis (mean [SD] age of 45.7 [14.40] years, 83.9% [281/335] female). At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The median (interquartile range) time to follow‐up appointment from initial appointment was 20.5 (13.3–35.3) weeks. The mean (SD) BP at baseline was systolic 124.7 (15) mmHg and diastolic 77 (11) mmHg, and at follow‐up was systolic 124.0 (15) mmHg and diastolic 77.8 (9) mmHg. Overall, 23.3% (78/335) of all patients had worsening BP, whereas 13/225 (3.9%) patients had improvement in their BP. Patients with atrial fibrillation were more likely to develop worsening BP (odds ratio, 4.9, 95% confidence interval 1.12–21.4; p = 0.035). There was no association between worsening BP and pre‐existing hypertension, sex, body mass index, or age. One patient had non‐ST elevation myocardial infarction attributed to a hypertensive emergency while on erenumab. Conclusion We found that 23.3% of patients initiated on erenumab may have developed worsening BP, suggesting the need for BP monitoring in patients initiated on erenumab.

Abstract Introduction Sleep-related painful erection (SRPE) is a rare parasomnia characterized by painful penile erections during rapid eye movement sleep. Normal, painless erections continue to occur while awake. Approximately thirty cases have been reported in the literature. Multiple theories about potential pathophysiology have been proposed including neurologic dysfunction of the ischiocavernosus and bulbocavernosus, correlation with obstructive sleep apnea, and/or autonomic dysfunction. There is no known single effective treatment to date resulting in durable response despite multiple attempts at therapy. Report of case(s) A 39-year-old male presented with SRPE. This started in 2018 and occurred in the second half of the night every twenty minutes, contributing to discomfort and poor sleep quality. While awake, his erections were painless. He was prescribed baclofen at doses up to 30mg daily decreasing episode frequency to 1-6 times per night, but disabling somnolence precluded continuation. Pelvic physiotherapy was unhelpful while imipramine and clonazepam provided partial relief. Tadalafil was ineffective and cinitapride was not available in the United States. Oxycodone used for pain after a motor vehicle accident did effectively treat him for five hours per night, so morphine was trialed. This was effective for two weeks, but symptoms returned. In April 2022, he was begun on sodium oxybate. With an initial dose of 2.25 g twice nightly, symptoms were treated for four hours a night. After increasing to 2.75 g twice nightly, the SRPE was effectively treated. As of September 2022, he is taking sodium oxybate 3 g at bedtime, 3 g 3.5 hours later and the final 3 g at the 7th hour, promoting 9.5 hours of sleep without SRPE. Conclusion This 39-year-old male who presented with SRPE was trialed on multiple therapies without success, and ultimately successfully treated with an appropriate and titrated dose of sodium oxybate. This may represent a new treatment option, which we hypothesize may act by modulating GABA to result in relaxation of the bulbospongiosus and ischiocavernosus muscles. Further studies should include the study of both the efficacy of this drug for SRPE as well as potential mechanisms of action. Support (if any)

Introduction Transient Ischemic Attack (TIA) evaluation requires urgent etiology identification and targeted stroke prevention, traditionally performed via hospital admission. The literature suggests that outpatient evaluation may be safe and cost‐effective. Hence, we implemented an expedited outpatient pathway (OP) for patients presenting to our institution’s Emergency Department (ED) with TIA. To further guide future practice, we compared clinical features and outcomes between expedited OP and our well‐established inpatient pathway (IP). Methods We implemented an algorithm of direct communication between ED providers and Vascular Neurologists for all TIA patients. Certain screening studies (head CT, CT angiogram, basic laboratories) and acute therapies were implemented in the ED, whereas others (brain MRI, echocardiogram, etc) and Vascular Neurology consultations were expedited outpatient within 48–72 hours.We included all patients that underwent OP evaluation from May 2021‐May 2022. Further, we extracted patients with a final diagnosis of TIA and compared them with IP TIA patients hospitalized (2017‐2021), matched by age, gender, and clinical severity (ABCD2). Descriptive statistics were used to summarize patient demographics, clinical data, treatments, and 3‐month outcomes. Continuous variables were summarized with mean and standard deviations while categorical variables were shown as counts and percentages. Chi‐square test was used for categorical variables and Mann‐Whitney U test was used to compare continuous variables. P‐values < 0.05 were considered statistically significant and all tests were two‐sided. Statistical Analysis was completed in R 4.0.3. Results Of 43 patients who underwent expedited OP TIA workup, TIA or minor stroke was diagnosed in 21/43 (48.9%). 18 TIAs underwent comparative analyses. Mean symptom duration was longer in the IP (2.06 hours) than OP (0.99 hours), p = 0.370%. TIA was more likely to be diagnosed in the OP 14/18 (78%) versus IP 12/18 (67%), (p = 0.423). OP had more transesophageal echocardiograms (17% vs 5%, p = 0.630) and longer duration of ambulatory cardiac monitoring (mean 574.3 vs 381.7 hours, p = 0.100). IP patients were more likely to get started on anticoagulation compared to OP (38% vs 11%, p = 0.258) and high‐intensity statin (38% vs 17%, p = 0.260). All laboratories, echocardiograms and brain MR imaging were performed significantly sooner for the IP (p< 0.05 for all). IP had higher rate of return ED visits (22%) and readmissions at 3 months (11%), whereas OP had none. OP had no deaths or recurrent strokes, whereas 11% and 5.6% respectively were noted in the IP at 3 months (p = 0.310, p = 0.310). Conclusions Our study shows that routine IP evaluation for patients presenting with TIA in the ED may not offer diagnostic superiority nor lead to improvement of short‐term clinical outcomes, as compared to the expedited OP evaluation. Careful evaluation of TIA patients in the ED followed by expedited OP evaluation might be a plausible approach to help lower costs and avoid hospitalization without compromising the safety of these patients.

Abstract Introduction Treatment recommendations for Peyronie's Disease (PD) differ based on whether a patient is in the acute/active versus chronic/stable phase of the disease, yet there are no agreed upon criteria for defining these clinical entities. Objectives To review the criteria used to define acute and chronic phase PD in modern PD intervention studies Methods We performed a search engine review to identify indexed publications for PD intervention studies and review articles / meta-analyses from the year 2011-2020. Outcomes results were catalogued and summarized across articles. As a result of the substantial heterogeneity of outcome measures and follow-up intervals, meta-analytic techniques were not applied to the data analysis. Results We identified a total of 104 studies that met inclusion criteria and had available information for review (n = 79 primary intervention studies; n = 25 review articles/meta-analyses/guidelines). Among the queried studies, we were unable to identify a consensus with respect to the criteria used to define acute and chronic phases of PD. 33% of primary intervention studies did not specifically define their criteria for acute and chronic phase PD, despite referencing these populations as part of the inclusion criteria in many instances. Studies used heterogenous criteria including total symptom duration, duration of “stable” symptoms, and presence/absence of pain. Conclusion Due to varying definitions across the literature, we were unable to create a standardized definition of acute and chronic phase Peyronie's in terms of time. Our findings emphasize the need for greater consensus in defining the treatment cohorts with future studies that assess treatment for men with PD.