Reversible cerebral vasoconstriction syndrome associated with interferon beta-1a use for multiple sclerosis.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) has been associated with multiple medications, cocaine, pregnancy, migraine, and other conditions. OBJECTIVES: RCVS associated with interferon beta use has never before been described. METHODS: We describe the case of a 20-year-old female who developed acute onset severe headache and was found to have subarachnoid hemorrhage 2 months after initiating Rebif (Interferon beta-1a) for multiple sclerosis (MS). Cerebral angiography showed multiple areas of distal stenosis and dilatation with radiographic resolution 1 month later. RESULTS/CONCLUSIONS: This is the first case report of RCVS in an MS patient treated with Rebif.

Optic Neuropathy and Stroke Secondary to Invasive Aspergillus in an Immunocompetent Patient.

Angioinvasive aspergillosis is an aggressive fungal infection that is potentially life threatening without prompt treatment. Optic nerve involvement of Aspergillus can mimic optic neuritis commonly seen in demyelinating and other inflammatory conditions. Treatment of Aspergillus infection with steroids may worsen the clinical course. We describe a unique case of disseminated central nervous system aspergillosis, initially presenting as an optic neuropathy, with subsequent stroke in multiple vascular territories.

Fingolimod therapy for multiple sclerosis.

Because of its potent efficacy and oral route of administration, the approval of fingolimod as treatment for relapsing-remitting multiple sclerosis (MS) was highly anticipated. The therapeutic and adverse effects are mediated by modulation of sphingosine 1-phosphate receptors. Fingolimod inhibits the egress of lymphocytes from lymph nodes and may also have direct effects on the central nervous system. The clinical trials that led to the approval of fingolimod demonstrated benefit on relapses, disability progression, magnetic resonance imaging (MRI) activity, and brain volume loss in treatment-naïve and previously treated patients with relapsing-remitting MS. The use of fingolimod in clinical practice has been limited by concerns for cardiac effects, infection, and macular edema as well as the relative lack of long-term safety data for this drug with a novel mechanism of action. Additional clinical trial and postmarketing data suggest that fingolimod is a safe, effective, and well-tolerated treatment option when patients are selected and monitored appropriately.

Disparities in spatial access to neurological care in Appalachia: a cross-sectional health services analysis.

Background: Appalachia is rural and socioeconomically deprived with a heavy burden of neurological disorders and poor access to healthcare providers. Rates of neurological disorders are increasing over time without equal increases in providers, indicating that Appalachian disparities are likely to worsen. Spatial access to neurological care has not been robustly explored for U.S. areas, so we aimed to examine disparities in the vulnerable Appalachian region. Methods: Using 2022 CMS Care Compare physician data, we conducted a cross-sectional health services analysis, where we computed spatial accessibility of neurologists for all census tracts in the 13 states with Appalachian counties. We stratified access ratios by state, area deprivation, and rural-urban commuting area (RUCA) codes then utilized Welch two-sample t-tests to compare Appalachian tracts with non-Appalachian tracts. Using stratified results, we identified Appalachian areas where interventions would have the largest impact. Findings: Appalachian tracts (n = 6169) had neurologist spatial access ratios between 25% and 35% lower than non-Appalachian tracts (n = 18,441; p < 0.001). When stratified by rurality and deprivation, three-step floating catchment area spatial access ratios for Appalachian tracts remained significantly lower in the most urban (RUCA = 1 [p < 0.0001) and most rural tracts (RUCA = 9 [p = 0.0093]; RUCA = 10 [p = 0.0227]). We identified 937 Appalachian census tracts where interventions can be targeted. Interpretation: After stratifying by rural status and deprivation, significant disparities in spatial access to neurologists remained for Appalachian areas, indicating both poorer access in Appalachia and that neurologist accessibility cannot be determined solely by remoteness and socioeconomic status. These findings and our identified disparity areas have broad implications for policymaking and intervention targeting in Appalachia. Funding: R.B.B. was supported by NIH Award Number T32CA094186. M.P.M. was supported by NIH-NCATS Award Number KL2TR002547.

Clinical Skills Evaluation in Neurology, Child Neurology and Psychiatry: Program Directors' Perspective and Future Opportunities.

BACKGROUND: When the American Board of Psychiatry and Neurology (ABPN) eliminated the oral segment of the board-certification examination, it began requiring in-training assessments termed Clinical Skill Evaluations (CSEs). OBJECTIVE: This study describes the experience of residency program directors (PDs) with CSEs and identifies opportunities for improvement. METHODS: A 23-question survey was administered electronically to neurology, child neurology, and psychiatry PDs assessing their CSE testing procedures in April 2019. Data from the ABPN preCERT® Credentialing System CSE was analyzed to corroborate the survey results. RESULTS: A total of 439 PDs were surveyed. The overall response rate was approximately 40% with a similar response across the 3 specialties. Overall, there was a strong enthusiasm for CSEs as they captured the essence of the physician-patient relationship. Most PDs encouraged trainees to attempt CSEs early in their training though the completion time frame varied by specialty. Approximately 57% of psychiatry residencies offered formal, in-person faculty training while less than one-fourth of neurology and child neurology programs offered such a program. Most PDs are interested in a faculty development course to ensure a standardized CSE testing process at their institution. CONCLUSIONS: This survey confirmed earlier findings that CSEs are usually implemented early in the course of residency training and that most PDs think it captures the essence of the physician-patient relationship. While few residencies offer a CSE training course, there is widespread support for a formal approach to faculty development and this offers a specific opportunity for CSE improvement in the future.

Technology-enabled assessments to enhance multiple sclerosis clinical care and research.

BACKGROUND: Comprehensive and efficient assessments are necessary for clinical care and research in chronic diseases. Our objective was to assess the implementation of a technology-enabled tool in MS practice. METHOD: We analyzed prospectively collected longitudinal data from routine multiple sclerosis (MS) visits between September 2015 and May 2018. The MS Performance Test, comprising patient-reported outcome measures (PROMs) and neuroperformance tests (NPTs) self-administered using a tablet, was integrated into routine care. Descriptive statistics, Spearman correlations, and linear mixed-effect models were used to examine the implementation process and relationship between patient characteristics and completion of assessments. RESULTS: A total of 8022 follow-up visits from 4199 patients (median age 49.9 [40.2-58.8] years, 32.1% progressive course, and median disease duration 13.6 [5.9-22.3] years) were analyzed. By the end of integration, the tablet version of the Timed 25-Foot Walk was obtained in 89.0% of patients and the 9-Hole Peg Test in 94.8% compared with 74.2% and 64.3%, respectively before implementation. The greatest increase in data capture occurred in processing speed and low-contrast acuity assessments (0% prior vs 78.4% and 36.7%, respectively, following implementation). Four PROMs were administered in 41%-98% of patients compared with a single depression questionnaire with a previous capture rate of 70.6%. Completion rates and time required to complete each NPT improved with subsequent visits. Younger age and lower disability scores were associated with shorter completion time and higher completion rates. CONCLUSIONS: Integration of technology-enabled data capture in routine clinical practice allows acquisition of comprehensive standardized data for use in patient care and clinical research.

Tuberculosis screening in multiple sclerosis: effect of disease-modifying therapies and lymphopenia on the prevalence of indeterminate TB screening results in the clinical setting.

BACKGROUND: Tuberculosis screening is recommended in multiple sclerosis patients starting certain disease-modifying therapies. Disease-modifying therapies may affect interferon-gamma release assay results. OBJECTIVE: To determine the effects of multiple sclerosis disease-modifying therapies on interferon-gamma release assay results. METHODS: Indeterminate interferon-gamma release assay results among multiple sclerosis patients were compared across disease-modifying therapies by Fisher's exact test. Logistic regression evaluated the effects of lymphopenia on interferon-gamma release assay results. RESULTS: A total of 1058 patients underwent interferon-gamma release assay: 2.0% (21) positive, 6.1% (65) indeterminate, with 59.4% (628) on disease-modifying therapies. Results were significantly different across disease-modifying therapies (P = 0.002). Absolute lymphocyte count less than 0.5 k/µL had 9.39 times (95% confidence interval 5.2-17.0) increased odds of indeterminate interferon-gamma release assay results. CONCLUSIONS: Disease-modifying therapies affecting lymphocytes had a higher risk of indeterminate interferon-gamma release assay results.

Triaging Patients with Multiple Sclerosis in the Emergency Department: Room for Improvement.

BACKGROUND: Patients with multiple sclerosis (MS) present to the emergency department (ED) for various reasons. Although true relapse is rarely the underlying culprit, ED visits commonly result in new magnetic resonance imaging (MRI) and neurology admissions. We studied ED visits in patients with MS and evaluated decision making regarding diagnostic/therapeutic interventions and visit outcomes. We identified potential areas for improvement and used the data to propose a triaging algorithm for patients with MS in the ED. METHODS: We reviewed the medical records from 176 ED visits for patients with MS in 2014. RESULTS: Ninety-seven visits in 75 patients were MS related (66.6% female; mean ± SD age, 52.6 ± 13.8 years; mean ± SD disease duration, 18.5 ± 10.5 years). Thirty-three visits were for new neurologic symptoms (category 1), 29 for worsening preexisting symptoms (category 2), and 35 for MS-related complications (category 3). Eighty-nine visits (91.8%) resulted in hospital admission (42.7% to neurology). Only 39% of ordered MRIs showed radiographic activity. New relapses were determined in 27.8% of the visits and were more prevalent in category 1 compared with category 2 (P = .003); however, the two categories had similar rates of ordered MRIs and neurology admissions. CONCLUSIONS: New relapse is a rare cause of ED visits in MS. Unnecessary MRIs and neurology admissions can be avoided by developing a triaging system for patients with MS based on symptom stratification.

Melanocortin-4 receptor-deficient mice are not hypertensive or salt-sensitive despite obesity, hyperinsulinemia, and hyperleptinemia.

The purpose of this study was to test whether the melanocortin-4 receptor (MC4R) is critical in the development of hypertension associated with obesity and its metabolic disorders. MC4R-deficient homozygous (-/-) and heterozygous (+/-) and wild-type (WT) C57BL/6J mice 17 to 19 weeks old (n=5 to 7 per group) were implanted with telemetry devices for monitoring 24-hour mean arterial pressure (MAP) and heart rate (HR). After 3-day stable control measurements on normal-salt diet (NSD; 0.4% NaCl), mice received a high-salt diet (HSD; 4% NaCl) for 7 days, followed by 3-day recovery on NSD. MC4R (-/-) mice were severely obese compared with MC4R (+/-) and WT mice (body weight 48+/-1.5 versus 31+/-0.6 and 30+/-0.5 g respectively). On NSD, MAP was similar in all groups of mice (MC4R (-/-) 110+/-3 mm Hg; MC4R (+/-) 109+/-2 mm Hg; WT 114+/-2 mm Hg), and HR in MC4R (-/-) was lower than in WT (604+/-5 versus 645+/-9 bpm; P<0.05) but not different from MC4R (+/-) (625+/-13 bpm) mice. HSD did not significantly alter MAP or HR in any of the groups. Epididymal and retroperitoneal fat weights and plasma leptin levels were several-fold greater in MC4R (-/-) compared with MC4R (+/-) and WT mice. Plasma insulin and glucose levels were also significantly greater in MC4R (-/-) than in MC4R (+/-) and WT mice. These data suggest that despite obesity, visceral adiposity, hyperleptinemia, and hyperinsulinemia, MC4R (-/-) mice are neither hypertensive nor salt sensitive, indicating that a functional MC4R may be necessary for the development of hypertension associated with obesity and its metabolic abnormalities.