Shane Poole

Background and ObjectivesNeuropsychological evaluations are essential for understanding cognitive dysfunction in multiple sclerosis (MS), but data embedded in narrative electronic health record (EH...

Introduction: Gait dysfunction is a common impairment in people with multiple sclerosis (PwMS), contributing to falls, reduced mobility, and lower quality of life. Functional electrical stimulation (FES) can address gait challenges but remains underutilized in MS care. This feasibility study evaluated the immediate effects of a novel multimuscle FES sleeve on spatiotemporal gait parameters in PwMS experiencing walking difficulties. Methods: Twenty adults with MS participated completed preferred- and fast-speed walking trials on an instrumented walkway with and without a wearable lower-extremity FES sleeve in a single-session study. Usability rating was assessed via survey. Spatiotemporal gait metrics were compared between conditions. Results: Responses indicated strong usability: 85% found the FES useful for self-management of walking symptoms; 95% agreed that FES would positively impact quality of life; 75% found it easy to use. FES use was associated with immediate improvements in gait stability, including reduced stride width variability and step length asymmetry, and increased walk ratio during preferred-speed walking. Reduced stride width variability was also observed during fast walking. Conclusions: This multimuscle wearable FES sleeve was highly acceptable to PwMS and demonstrated immediate improvements in their gait stability. Longitudinal studies are needed to evaluate long-term effectiveness and impact on mobility and participation.

Background: Gait impairment is common among people with multiple sclerosis (PwMS) and is an important marker of disease progression. However, gait assessments typically require in-person evaluations. Objective: To describe the pose-estimation-based method for estimating spatiotemporal gait parameters from a single consumer-grade video, and evaluate the feasibility of home video collection by PwMS. Methods: In a single-center longitudinal digital phenotyping study, ambulatory adults with MS completed a standardized walking task recorded in the frontal plane. Pose estimation (MediaPipe Pose, Ultralytics) and custom scripts were used to estimate gait parameters from videos. Participants were invited to record walking videos at home using personal devices. Adoption and technical feasibility were evaluated across two home video data acquisition phases, with iterative protocol refinements. Results: The in-clinic study included 132 participants; 55 contributed home videos. In Phase I, while home video adoption was low (45% [30/66]), 87% [26/30] uploaded ≥1 video of sufficient quality for gait analysis. After protocol refinements, 100% [25/25] uploaded ≥1 high-quality video. Overall, high-quality frontal-plane videos were obtained at similar rates at home (92% [97/105]) and in-clinic (91% [423/467]). Conclusions: Home walking videos can feasibly be collected by PwMS to estimate gait parameters, providing an accessible approach for remote gait monitoring.

Facial movements can be key indicators of neurological health and emotional state, offering insights into motor and neuropsychiatric functions that are disrupted in neurologic disorders. Neurological disease can present with characteristic differences in facial movements, like the masked facies of parkinsonism. Automated digital facial expression recognition could assist in asynchronous, remote and objective diagnostic processes. We hypothesized that facial movements relating to smiling, frowning, and blinking could be extracted from brief video-taped encounters in a clinic setting and used to (1) differentiate between neurologic diagnoses, and (2) identify people with symptoms of anxiety and depression. Using untargeted recruitment, individuals with multiple sclerosis (MS), other conditions (parkinsonism, frontotemporal dementia (FTD)), and healthy controls (HC) enrolled in an ongoing digital phenotyping study. Participant faces were video-recorded during a spontaneous language task. Videos were processed using OpenFace 2.2.0, an open-access digital tool pre-trained for facial landmark detection and facial action unit recognition. Participants with MS completed the General Anxiety Disorder-7 (GAD-7) and the Hospital Anxiety and Depression Scale (HADS-D). Videos were analyzed for adults with MS (n=151, mean age 48, 72% female), parkinsonism (n=23, mean age 67, 35% female), FTD (n=14, mean age 68, 29% female), and HCs (n=33, mean age 55, 58% female). Sampling duration was 60-90 seconds; 91% videos passed quality control. Individuals with parkinsonism had decreased eye-blinking compared to all groups, and decreased smiling and increased brow-lowering compared to MS and HCs. Individuals with FTD had increased blinking relative to other groups. There were no significant differences between individuals with MS and HCs. Classification accuracy for partition analysis model was 88% (ROC-AUC 0.84 for parkinsonism). In individuals with MS, decreased variability in brow lowerering was seen with higher anxiety symptoms, and decreased cheek raising intensity was seen with higher depression symptoms. Digitally identified facial movements have face validity for recapitulating known clinical characteristics of neurological disease, as well as reflecting internal state relating to mood. This provides a foundation for expanded longitudinal validation of computer vision-based facial movement analysis in neurological research. However, findings should be interpreted in the context of sample size imbalance across diagnostic groups, which may have influenced classification performance.

Background: Bladder dysfunction affects over 85% of people with multiple sclerosis (PwMS), yet current assessment methods are limited to periodic in‐clinic evaluations or subjective patient reports, failing to capture real‐world symptom fluctuations.Objectives: To evaluate the feasibility and validity of using a novel remote bladder ultrasound device for home monitoring of bladder dysfunction in PwMS, comparing remote measurements with standard clinical assessments.Methods: Twenty‐two women with MS participated in this 3‐month pilot study. Participants were asked to use the wearable ultrasound device at home for at least 3–5 days a month. Remote device measurements were compared with standard clinical data for post‐void residual (rPVR vs. cPVR) and urinary frequency (rFrequency vs. 3‐day bladder diary frequency). Agreement between measures was assessed using Bland–Altman analyses and correlation coefficients.Results: Participants were middle‐aged (mean 51.5 years; SD 9.3) with mild–moderate disability (median EDSS 4.0) and mostly relapsing MS (72.7%). Study retention was high (86.4%; 19/22), with mean device utilization of 14.1 days. Good agreement was seen between rPVR and cPVR (mean difference = 32.1 mL, SD = 38.6; 95% limits of agreement: −43.6, 107.9). The rFrequency measure also demonstrated a strong correlation with patient‐reported frequency (ICC = 0.81, Pearson's r = 0.793, p = 0.002). Visualization of remote monitoring data revealed substantial day‐to‐day variability in bladder symptoms not captured by traditional assessments.Conclusion: This pilot study demonstrates the feasibility and preliminary validity of using wearable ultrasound technology for remote monitoring of bladder dysfunction in PwMS. The ability to capture real‐world symptom variations could transform assessment and management approaches, enabling more personalized and responsive care strategies.

Neutropenia is described as a rare adverse event associated with B cell-depleting therapy (BCDT) use in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, little is known about longitudinal clinical outcomes. We estimated the real-world incidence of neutropenia among patients with neuroinflammatory disease treated with BCDT and characterized the clinical course. We conducted a retrospective cohort study using electronic medical records to estimate the incidence rate of neutropenia in adults with MS/NMOSD from a neuroimmunology clinic in California between January 6, 2006, and November 2, 2015, treated with ocrelizumab, rituximab, ofatumumab, ublituximab, or inebilizumab. Each clinical course (recurrence, time to recovery of absolute neutrophil count [ANC], postneutropenia treatment) of neutropenia was then presented in a case series. In this cohort of 1,825 patients (6,009 person-years on BCDT), the largest cohort addressing this question to date, 37 developed neutropenia. The estimated incidence rate of neutropenia was 0.62 (95% CI 0.45-0.85) per 100 person-years. The median time from last infusion of current BCDT was 4 months (interquartile range [IQR] 1-6). The median nadir ANC was 390 (IQR 40-960); the nadir ANC was 0 for 6 patients (16%). All patients ultimately recovered to normal counts, except 2 patients developing fluctuating ANCs for months. Among the 32 patients not receiving filgrastim, the median time to ANC recovery was 11 days (95% CI 7-26). Course severity was asymptomatic/mild in 32% (n = 12) while 54% (n = 20) required hospitalization. A confirmed simultaneous infection or infectious prodrome occurred in 23 (62%). After recovery, 30 patients (81%) continued BCDT and 2 (7%) changed within BCDT class. Neutropenia recurred in 13 patients (35%), including 3 who discontinued BCDT after initial neutropenia. The estimated incidence rate of recurrent neutropenia was 0.22 (95% CI 0.13-0.39) per 100 person-years. The mean (SD) time to recurrence from initial neutropenia was 251 (SD: 355) days. This study is comprehensive and reflects a large cohort, examining incidence rates of neutropenia with BCDT in MS and NMOSD. Overall, neutropenia was still rare, occurring at a rate of 0.66 per 100 person-years, and infections were associated triggers in some patients. Yet, of relevance to clinicians, neutropenia was not benign: half required hospitalization and 35% experienced recurrence, which is higher than what was reported in clinical trials.

This single-center retrospective cohort study sought to characterize the clinical spectrum of small vessel predominant primary CNS vasculitis (sv-PCNSV) and to investigate the impact of early intensive immunosuppressive therapy on remission. We analyzed data of patients diagnosed with biopsy-proven sv-PCNSV at our institution between 2009 and 2023. "Early intensive treatment" (EIT) was defined by cyclophosphamide therapy within 3 months of immunosuppressive treatment initiation. Patients in the "escalation treatment" (ESC) group initially received glucocorticoids, either as monotherapy or in conjunction with azathioprine, mycophenolate mofetil, or methotrexate. Twenty-six patients (50% female) met the study criteria, including 7 with amyloid-beta-related angiitis (ABRA). The median age at onset was 55.5 years (range 20-82), and headache (76.9%) and altered mental status (61.5%) were common presenting symptoms. Neuroimaging commonly showed bihemispheric T2/FLAIR lesions (77%) and abnormal gadolinium enhancement (88.5%), but intracranial vascular irregularities indicating large or medium vessel involvement were rare (11.5%). Among patients with non-ABRA sv-PCNSV (n = 19), some demonstrated spinal cord involvement (15.8%) and others exhibited isolated unihemispheric disease (21.1%). Although CSF testing (n = 23) often demonstrated mild pleocytosis, a notable minority of patients (17.4%) had a normal CSF analysis. Six patients (23.1%) underwent repeat brain biopsy because of initial nondiagnostic findings. Remission was achieved in all patients in the EIT group (n = 12/12), in contrast to 78.6% of patients in the ESC group (n = 11/14). Time to remission was significantly shorter among patients in the EIT group compared with the ESC group (median 5 vs 19 months, hazard ratio = 0.24, 95% CI [0.10-0.63], p < 0.005). Most patients achieving remission continued maintenance therapy, with an overall relapse rate of 19%. This study highlights the considerable clinical heterogeneity in sv-PCNSV, a rare but serious condition. Early, aggressive treatment with cyclophosphamide is associated with a shorter time to remission, and further validation in prospective studies is warranted.

Objective: Wearable devices can monitor key health and fitness domains. In multiple sclerosis (MS), monitoring step count and sleep is feasible, valid, and offers a holistic glimpse of patient functioning and worsening. However, data generated from wearables are typically unavailable at the point of care. We describe the design, development, and evaluation of a proof‐of‐concept tool that delivers patient‐generated wearables data in accessible, interpretable, and actionable formats to an outpatient Neurology clinic.Methods: Through a process of human‐centered design, stakeholders were engaged to create a technological solution to access and display wearables data via a launch from the electronic health record (EHR). Designs were informed by patient‐centered observational research and clinician interviews to ensure user alignment and validity. Qualitative and quantitative evaluations (Health ITUES framework) as well as live observations of use assessed functionality, ease of use, and clinical integration.Results: During development, 25 clinicians and four engineers across eight clinical settings provided feedback. The proof‐of‐concept wearable selected was Fitbit, which was connected via a custom solution to the EHR dashboard (BRIDGE). In the final validation, clinician satisfaction was high: mean scores > 4/5 for all performance and ease of use components. Live visualizations during clinical encounters highlighted a range of potential uses: detecting progression by step count, setting motivating and realistic activity goals despite limitations, referring to rehabilitation after activity drops, and measuring effects of interventions on sleep quality.Interpretation: Integrating wearables data into a clinical workflow for neurology is feasible and highlights novel areas to support shared decision‐making and data‐driven, personalized care.

The impact of menopause on the brain is not well understood. Hormonal changes, including puberty and pregnancy, influence the onset and course of multiple sclerosis (MS). After menopause, a worsening of MS disease trajectory measured on the clinician-rated Expanded Disability Status Scale (EDSS) was reported in some, but not all, studies. Evaluating the association between menopause and more objective measures of CNS injury is warranted. This study sought to assess the trajectory of objective functional outcomes and disease biomarkers in women with MS before and after menopause in a longitudinal prospective observational cohort. Data were collected prospectively from a longitudinally followed MS cohort, including the performance-based Multiple Sclerosis Functional Composite (MSFC) as the primary functional outcome and the paraclinical marker of neuronal injury serum neurofilament light chain (sNfL) as the primary biomarker outcome. Outcomes were analyzed using segmented linear mixed model regressions adjusted for age, BMI, and tobacco use, with a change in slope at the time of menopause, as the a priori inflection point. One hundred and eighty-four postmenopausal women met inclusion criteria. Participants were followed for a median of 13 years (interquartile range [IQR] = 4, range: 1-17). The median MS duration was 24 years (IQR = 13, range: 3-64), and the median EDSS score was 2.5 (IQR = 2, range: 0-8). The median age at natural menopause was 50 years (IQR = 5, range: 33-60); 17% of participants used any systemic menopausal hormone therapy. Menopause reflected an inflection point in MSFC worsening (slope difference 0.08, 95% CI 0.01, 0.14, p = 0.0163) and increase in serum neurofilament light chain (slope difference -0.95, 95% CI -1.74 to -0.16, p = 0.0194) while the opposite was found for EDSS (slope difference 0.05, 95% CI 0.01-0.09, p = 0.0200). Findings remained significant after adjustment for multiple covariates. When using additional nonlinear regression modeling, similar inflection points were found (within 3 years of the final menstrual period) for sNfL and EDSS but not MSFC. The menopausal transition may represent an inflection in accumulation of neuronal injury and functional decline in MS.

Background: Patients with multiple sclerosis (MS) on some disease-modifying therapies (i.e., natalizumab), report a “wearing-off” effect characterized by increased symptoms directly before infusions. Prior research suggests this may reflect natural MS fluctuations rather than true treatment waning; however, this has not been confirmed for anti-CD20 agents (e.g., ocrelizumab). Daily step count (STEPS) can reflect overall function. This study examined temporal associations between anti-CD20 therapy infusions and STEPS. Methods: Retrospective analysis evaluated data from two Fitbit-monitored cohorts ( N = 145 total, 32 anti-CD20-treated participants) across 60 treatment cycles. Monthly STEPS were recorded directly pre- and three-month post-infusion over the six-month treatment intervals. Mixed-effects models evaluated the relationship between infusion timing, STEPS, and participant demographics, controlling for confounding variables. Results: No significant difference in STEPS was observed pre- versus post-infusion ( p = 0.32). An average decrease of 3.3% was noted post-infusion but was not statistically significant. No associations between STEPS and participant characteristics (e.g., age, disability level) were identified. Individual variability existed, but no clear group-level trends emerged. Conclusions: This study found no evidence of an association between timing of anti-CD20 infusion and changes in STEPS. Findings highlight the need for integrating objective measures with patient-reported outcomes and biomarkers in future research to better understand potential treatment fluctuations.