Evaluating noninvasive brain stimulation to treat overactive bladder in individuals with multiple sclerosis: a randomized controlled trial protocol.

BACKGROUND: Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD. METHODS: By employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS. DISCUSSION: Some limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023.

Social determinants of health and disparate disability accumulation in a cohort of Black, Hispanic, and White patients with multiple sclerosis.

BACKGROUND: Black and Hispanic patients with multiple sclerosis (MS) have been shown to accumulate greater multiple sclerosis-associated disability (MSAD) than White patients. Disparities in social determinants of health (SDOH) among these groups have also been reported. OBJECTIVE: To determine the extent to which associations of race and ethnicity with MSAD may be attributable to differences in SDOH. METHODS: Retrospective chart analysis of patients at an academic MS center grouped by self-identified Black (n = 95), Hispanic (n = 93), and White (n = 98) race/ethnicity. Individual patient addresses were geocoded and matched with neighborhood-level area deprivation index (ADI) and social vulnerability index (SVI). RESULTS: Average Expanded Disability Status Scale (EDSS) scores at last-recorded evaluations of White patients (1.7 ± 2.0) were significantly lower than Black (2.8 ± 2.4, p = 0.001) and Hispanic (2.6 ± 2.6, p = 0.020) patients. Neither Black race nor Hispanic ethnicity was significantly associated with EDSS in multivariable linear regression models that included individual-level SDOH indicators and either ADI or SVI. CONCLUSION: Black race and Hispanic ethnicity are not significantly associated with EDSS in models that include individual and neighborhood-level SDOH indicators. Further research should elucidate mechanisms by which structural inequities affect MS disease course.

Disruption of specific white matter tracts is associated with neurogenic lower urinary tract dysfunction in women with multiple sclerosis.

OBJECTIVE: To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of neurogenic lower urinary tract dysfunction (NLUTD) in two independent cohorts of women with multiple sclerosis (MS) and NLUTD. METHODS: Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of 10 women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and functional MRI (fMRI) protocol, except that the validation MS cohort underwent 7-Tesla fMRI scan. Fifteen WMTs (six coursing to relevant brainstem areas) involved in bladder control were a priori regions of interest (ROI). Spearman's correlation test was performed between each the Fractional Anisotropy (FA) and mean diffusivity (MD) of each WMT and the clinical parameters. RESULTS: Overall, we found a very high degree of overlap (100% of a priori ROI) in the tracts identified by our correlation analysis as having the greatest contribution to NLUTD symptoms in MS women. The right inferior cerebellar peduncle, left posterior limb of internal capsule, and left superior cerebellar peduncle displayed significant associations to the greatest number of clinical parameters. CONCLUSIONS: Our correlation analysis supports the role of specific WMT disruptions in the contribution of symptoms in women with MS and NLUTD, as confirmed in two independent MS cohorts.

Predicting multiple sclerosis severity with multimodal deep neural networks.

Multiple Sclerosis (MS) is a chronic disease developed in the human brain and spinal cord, which can cause permanent damage or deterioration of the nerves. The severity of MS disease is monitored by the Expanded Disability Status Scale, composed of several functional sub-scores. Early and accurate classification of MS disease severity is critical for slowing down or preventing disease progression via applying early therapeutic intervention strategies. Recent advances in deep learning and the wide use of Electronic Health Records (EHR) create opportunities to apply data-driven and predictive modeling tools for this goal. Previous studies focusing on using single-modal machine learning and deep learning algorithms were limited in terms of prediction accuracy due to data insufficiency or model simplicity. In this paper, we proposed the idea of using patients' multimodal longitudinal and longitudinal EHR data to predict multiple sclerosis disease severity in the future. Our contribution has two main facets. First, we describe a pioneering effort to integrate structured EHR data, neuroimaging data and clinical notes to build a multi-modal deep learning framework to predict patient's MS severity. The proposed pipeline demonstrates up to 19% increase in terms of the area under the Area Under the Receiver Operating Characteristic curve (AUROC) compared to models using single-modal data. Second, the study also provides valuable insights regarding the amount useful signal embedded in each data modality with respect to MS disease prediction, which may improve data collection processes.

Altered bladder-related brain network in multiple sclerosis women with voiding dysfunction.

OBJECTIVES: A number of neurourology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamic study (UDS)/functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥6 months and symptomatic voiding phase neurogenic lower urinary tract dysfunction (NLUTD) underwent UDS/fMRI evaluation with a task of bladder filling/emptying that was repeated three to five times. We quantitatively compared their FC within 17 bladder-related brain regions during two UDS phases: "strong desire to void" and "(attempt at) voiding initiation." RESULTS: At "strong desire to void," the healthy group showed significantly stronger FC in regions involved in bladder filling and suppression of voiding compared to the patient group. These regions included the bilateral anterior cingulate cortex, right supplementary motor area, and right middle frontal gyrus. During "(attempt at) voiding initiation," healthy subjects exhibited stronger FC in the right inferior frontal gyrus compared to MS patients. CONCLUSION: Our study offers a new way to identify alterations in the neural mechanisms underlying NLUTD and provides potential targets for clinical interventions (such as cortical neuromodulation) aimed at restoring bladder functions in MS patients.

Exoskeleton-assisted Gait Training in Persons With Multiple Sclerosis: A Single-Group Pilot Study.

OBJECTIVE: To investigate the feasibility of conducting exoskeleton-assisted gait training (EGT) and the effects of EGT on gait, metabolic expenditure, and physical function in persons with multiple sclerosis (MS). DESIGN: Single-group pilot study. SETTING: Research laboratory in a rehabilitation hospital. PARTICIPANTS: Individuals with MS (N=10; mean age, 54.3±12.4y) and Expanded Disability Status Scale 6.0-7.5. INTERVENTIONS: All participants completed up to 15 sessions of EGT. MAIN OUTCOME MEASURES: Timed 25-foot walk test at self-selected and fast speed, 6-minute walk test, metabolic expenditure of walking and timed Up and Go test were assessed during walking without the exoskeleton at baseline and immediate post training. RESULTS: All participants tolerated the training intensity and completed training without adverse events. After training, gait speed was improved and metabolic expenditure was reduced significantly during the timed 25-foot walk test at self-selected speed. CONCLUSIONS: EGT is not only feasible but may also improve gait efficiency for persons with MS. Our observed improvement in gait speed was associated with reduced metabolic expenditure, which was likely because of improved neuromotor coordination. Further studies are required to investigate the effectiveness and integration of EGT in the continuum of MS rehabilitation.

Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

Mapping the trajectory of the amygdalothalamic tract in the human brain.

Although the thalamus is not considered primarily as a limbic structure, abundant evidence indicates the essential role of the thalamus as a modulator of limbic functions indirectly through the amygdala. The amygdala is a central component of the limbic system and serves an essential role in modulating the core processes including the memory, decision-making, and emotional reactions. The amygdalothalamic pathway is the largest direct amygdalo-diencephalic connection in the primates including the human brain. Given the crucial role of the amygdalothalamic tract (ATT) in memory function and diencephalic amnesia in stroke patients, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. To date, few diffusion-weighted studies have focused on the amygdala, yet the fine neuronal connection of the amygdala and thalamus known as the ATT has yet to be elucidated. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the ATT in the human brain. We studied 15 healthy right-handed human subjects (12 men and 3 women with age range of 24-37 years old). Using a high-resolution diffusion tensor tractography technique, for the first time, we were able to reconstruct and measure the trajectory of the ATT. We further revealed the close relationship of the ATT with the temporopontine tract and the fornix bilaterally in 15 healthy adult human brains.

Patient-specific 3D FLAIR for enhanced visualization of brain white matter lesions in multiple sclerosis.

PURPOSE: To improve the conspicuity of white matter lesions (WMLs) in multiple sclerosis (MS) using patient-specific optimization of single-slab 3D fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixteen MS patients were enrolled in a prospective 3.0T MRI study. FLAIR inversion time and echo time were automatically optimized for each patient during the same scan session based on measurements of the relative proton density and relaxation times of the brain tissues. The optimization criterion was to maximize the contrast between gray matter (GM) and white matter (WM), while suppressing cerebrospinal fluid. This criterion also helps increase the contrast between WMLs and WM. The performance of the patient-specific 3D FLAIR protocol relative to the fixed-parameter protocol was assessed both qualitatively and quantitatively. RESULTS: Patient-specific optimization achieved a statistically significant 41% increase in the GM-WM contrast ratio (P < 0.05) and 32% increase in the WML-WM contrast ratio (P < 0.01) compared with fixed-parameter FLAIR. The increase in WML-WM contrast ratio correlated strongly with echo time (P < 10-11 ). Two experienced neuroradiologists indicated substantially higher lesion conspicuity on the patient-specific FLAIR images over conventional FLAIR in 3-4 cases (intrarater correlation coefficient ICC = 0.72). In no case was the image quality of patient-specific FLAIR considered inferior to conventional FLAIR by any of the raters (ICC = 0.32). CONCLUSION: Changes in proton density and relaxation times render fixed-parameter FLAIR suboptimal in terms of lesion contrast. Patient-specific optimization of 3D FLAIR increases lesion conspicuity without scan time penalty, and has potential to enhance the detection of subtle and small lesions in MS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:557-564.

Voiding Phase Dysfunction in Multiple Sclerosis: Contemporary Review of Terminology, Diagnosis, Management, and Future Directions.

Lower urinary tract symptoms (LUTS) are highly prevalent in individuals with multiple sclerosis (MS). However, assessment of these symptoms is often hindered by vague definitions or absence of screening in asymptomatic patients. It is crucial to exercise caution when applying the non-neurogenic definition of urinary retention in this population. For men with MS experiencing persistent and treatment-resistant LUTS, urodynamic studies should be used to identify the underlying causes of symptoms. Although numerous therapies are presently accessible for managing LUTS in MS, there is a need for further investigation into emerging treatments such as percutaneous tibial nerve, and noninvasive brain stimulation.

Functional assessment of the dural lymphatic vessels using dynamic contrast MRI in multiple sclerosis.

BACKGROUND AND PURPOSE: The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance. METHODS: This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T MRI system using intravenous contrast-enhanced fluid-attenuated inversion recovery MRI. Signal in the dural lymphatic vessel along the superior sagittal sinus was measured to calculate peak enhancement, time to maximum enhancement, wash-in and washout slopes, and the area under the time-intensity curve (AUC). Correlation analysis was performed to examine the relationship between the lymphatic dynamic parameters and the demographic and clinical characteristics, including the lesion load and the brain parenchymal fraction (BPF). RESULTS: Contrast enhancement was detected in the dural lymphatics in most patients 2-3 min after contrast administration. BPF had a significant correlation with AUC (p < .03), peak enhancement (p < .01), and wash-in slope (p = .01). Lymphatic dynamic parameters did not correlate with age, BMI, disease duration, EDSS, or lesion load. Moderate trends were observed for correlation between patient age and AUC (p = .062), BMI and peak enhancement (p = .059), and BMI and AUC (p = .093). CONCLUSION: Intravenous dynamic contrast MRI of the dural lymphatics is feasible and may be useful in characterizing its hydrodynamics in neurological diseases.

Unfolding the direct connectivity of the occipital cortex with the hypothalamic, septal and BNST nuclei of the human brain.

The hypothalamus plays essential roles in the human brain by regulating feeding, fear, aggression, reproductive behaviors, and autonomic activities. The septal nuclei and the bed nucleus of stria terminalis (BNST) are also known to be involved in control of autonomic, motivational, learning, emotional and associative processes in the human brain. Multiple animal dissection studies have revealed direct connectivity between central limbic gray matter nuclei and occipital cortex, particularly from the hypothalamic, septal and BNST nuclei. However, the detailed anatomy of this connectivity in the human brain has yet to be determined. The primary objective of this study was to explore the utility of high spatial and high angular resolution diffusion weighted tractography techniques for mapping the connectivity pathways between the occipital cortex and central limbic gray matter nuclei in the human brain. We studied 30 healthy adult human brains, delineated, and reconstructed the trajectory of the occipito-hypothalamic/septal/BNST for the first time in the human brain.

Trigeminal neuralgia in multiple sclerosis: Association with demyelination and progression.

BACKGROUND: Trigeminal neuralgia (TN) is a well-recognized symptom of multiple sclerosis (MS), yet its clinical characteristics related to MS subtype is poorly studied. Our aim was to evaluate whether development and clinical outcome of TN are influenced by MS phenotype. METHODS: In this retrospective cohort study, our database from 2007 to 2022 was reviewed to identify patients who had both the diagnosis of MS and TN, whether TN was an initial symptom of MS or developed later in diagnosis. A detailed medical history and treatment outcome was obtained. Pain status was assessed retrospectively using the Barrow Neurological Institute Pain Scale (BNI-PS), with BNI-PS I-III considered as good pain control and BNI-PS IV-V as poor pain control. RESULTS: 58 patients had MS-related TN. 44 patients had relapsing remitting multiple sclerosis (RRMS) at the time of TN diagnosis, 11 had secondary progressive multiple sclerosis (SPMS) at the time of TN diagnosis, and type of MS was not clear in 3 patients at the time of TN diagnosis (either RRMS or SPMS). Over a mean follow up of 18.8 (SD=10.9) years, 30 transitioned to SPMS. TN was refractory to medical management in 9 RRMS and 22 SPMS patients (p = 0.001). TN patients with RRMS required lower median number of pain medications compared to SPMS (p = 0.014). Brain MRI was available in 41 of the entire cohort. Of these, 27 patients had demyelinating lesions in the trigeminal sensory pathway and 14 did not. Patients with existing lesions had a higher chance of failure of medical management (74% versus 36%, p = 0.017) and required surgical intervention (55% versus 7%, p = 0.003). DISCUSSION: TN was not seen in primary progressive multiple sclerosis (PPMS). In patients who transitioned to SPMS, TN was more likely to be refractory to medical management. TN was more refractory in the presence of demyelinating plaque involving trigeminal sensory pathway.

Identifying the white matter pathways involved in multiple sclerosis-related tremor using diffusion tensor imaging.

Background: Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology. Objective: To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI). Methods: In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity. Results: This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d = 1.53, q < 0.001) and left corticospinal tract (d = 1.32, q < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [rsp] = -0.56, p < 0.001), and forceps minor of corpus callosum (rsp = -0.45, p < 0.01). Conclusion: MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit.

Characterizing the time course of cerebrovascular reactivity in multiple sclerosis.

BACKGROUND AND PURPOSE: Changes in cerebral perfusion occur early in relapsing and progressive multiple sclerosis (MS) patients, though whether cerebral blood flow (CBF) can be altered by therapy is unknown. We sought to characterize the time course of change in CBF (cerebral vascular reactivity [CVR]), following intravenous (IV) acetazolamide (ACZ) in whole brain and within various gray and white matter brain regions in MS patients. METHODS: We enrolled five relapsing MS patients on injectable therapies. Participants received a 1000 mg IV bolus of ACZ and CBF was measured using pseudocontinuous arterial spin labeling MRI. To quantify differences in time course between patients, we calculated the numerical integration of CVR over time using the trapezoidal rule to estimate area under the curve (AUC(CVR) ). RESULTS: A change in whole brain CBF of 30%-65% was seen in all participants at 15 minutes after ACZ challenge. CBF increases >20% above baseline were sustained for 90 minutes within whole-brain, normal-appearing white matter and total T2-hyperintense lesioned tissue. AUC(CVR) values for both gray (cortical and deep gray matter) and white (normal-appearing and T2-lesioned) matter regions were similar between patients. CONCLUSION: Our findings show a prolonged time course in vascular reactivity after ACZ stimulus in MS patients with a similar time course for both gray and white matter brain regions, including in previously injured tissue. Our preliminary results suggest that blood flow can be augmented in the established MS lesion suggesting that even previously injured tissue might be responsive to treatment.

Evaluation of Muscle Synergy During Exoskeleton-Assisted Walking in Persons With Multiple Sclerosis.

OBJECTIVE: Gait deficit after multiple sclerosis (MS) can be characterized by altered muscle activation patterns. There is preliminary evidence of improved walking with a lower limb exoskeleton in persons with MS. However, the effects of exoskeleton-assisted walking on neuromuscular modifications are relatively unclear. The objective of this study was to investigate the muscle synergies, their activation patterns and the differences in neural strategies during walking with (EXO) and without (No-EXO) an exoskeleton. METHODS: Ten subjects with MS performed walking during EXO and No-EXO conditions. Electromyography signals from seven leg muscles were recorded. Muscle synergies and the activation profiles were extracted using non-negative matrix factorization. RESULTS: The stance phase duration was significantly shorter during EXO compared to the No-EXO condition (p<0.05). Moreover, typically 3-5 modules were extracted in each condition. The module-1 (comprising Vastus Medialis and Rectus Femoris muscles), module-2 (comprising Soleus and Medial Gastrocnemius muscles), module-3 (Tibialis Anterior muscle) and module-4 (comprising Biceps Femoris and Semitendinosus muscles) were comparable between conditions. During EXO condition, Semitendinosus and Vastus Medialis emerged in module-5 in 7/10 subjects. Compared to No-EXO, average activation amplitude was significantly reduced corresponding to module-2 during the stance phase and module-3 during the swing phase during EXO. CONCLUSION: Exoskeleton-assistance does not alter the existing synergy modules, but could induce a new module to emerge, and alters the control of these modules, i.e., modifies the neural commands indicated by the reduced amplitude of the activation profiles. SIGNIFICANCE: The work provides insights on the potential underlying mechanism of improving gait functions after exoskeleton-assisted locomotor training.

Predictors for outcomes of noninvasive, individualized transcranial magnetic neuromodulation in multiple sclerosis women with neurogenic voiding dysfunction.

Purpose: Multiple sclerosis (MS) is a multifocal demyelinating disease that affects the central nervous system (CNS) and commonly leads to neurogenic lower urinary tract dysfunction (NLUTD). Proper storage and release of urine relies on synchronized activity of the LUT, which is meticulously regulated by supraspinal circuits, making it vulnerable to diseases such as MS. NLUTD, characterized by voiding dysfunction (VD), storage issues, or a combination of both is a common occurrence in MS. Unfortunately, there are limited treatment options for NLUTD, making the search for alternative treatments such as transcranial rotating permanent magnet stimulation (TRPMS) of utmost importance. To assess effectiveness of treatment we also need to understand underlying factors that may affect outcomes, which we addressed here. Methods: Ten MS subjects with VD and median age of 54.5 years received daily TRPMS sessions for two weeks. Five pre-determined regions of interest (ROIs) known to be involved in the micturition cycle were modulated (stimulated or inhibited) using TRPMS. Clinical data (non-instrumented uroflow and urodynamics parameters, PVR, bladder symptom questionnaires) and neuro-imaging data were collected at baseline and following TRPMS via 7-Tesla Siemens MAGNETOM Terra magnetic resonance imaging (MRI) scanner. Each participant underwent functional MRI (fMRI) concurrently with a repeated urodynamic study (UDS). Baseline data of each arm was evaluated to determine any indicators of successful response to treatment.

Racial and ethnic disparities in treatment response and tolerability in multiple sclerosis: A comparative study.

BACKGROUND: Inter-individual response and tolerability profiles associated with available disease-modifying treatments (DMTs) are an important aspect of the therapeutic decision-making process in multiple sclerosis (MS). In the absence of racially diverse clinical studies, the possible effect of race and ethnicity on treatment outcome remains uncertain. This study aims to compare disease outcome among Hispanic, Black, and White patients with MS, and assess the impact of race/ethnicity on long-term outcome. METHODS: A retrospective review of electronic medical records was performed on a multiethnic cohort of MS patients treated in a large academic center. Sociodemographic characteristics, treatment regimens, and disability outcomes were compared between the three groups. RESULTS: A total of 300 age- and gender-matched MS patients (100 Hispanic, 100 Black, and 100 White) were included in the study. When assessing the overall survival of MS patients without ambulatory disability 5 years from diagnosis, Hispanics and Blacks attained lower survival times compared to Whites (survival time ratio [STR] 0.17, p = 0.004; and 0.14, p = 0.002, respectively). Black patients had the highest rate of disease progression and treatment-limiting adverse events despite similar sociodemographic profiles and DMT exposure relative to Hispanics and Whites. CONCLUSION: Racial/ethnic disparities in treatment outcome create an unmet need to identify tailored, multifaceted approaches to therapy selection in MS.

Assessment of Racial/Ethnic Disparities in Volumetric MRI Correlates of Clinical Disability in Multiple Sclerosis: A Preliminary Study.

BACKGROUND AND PURPOSE: Although global and regional brain volume has been established as a relevant measure to define and predict multiple sclerosis (MS) severity, characterization of specific trends by race/ethnicity is currently lacking. We aim to (1) characterize racial disparities in disability-specific patterns of brain MRI volumetric measures between Hispanic and Caucasian individuals with MS and (2) explore the relevance of these measures as predictors of clinical disability progression. METHODS: Brain MRI scans from 94 Hispanic and 94 age- and gender-matched Caucasian MS patients were analyzed using automatic and manual segmentation techniques. Select global and regional volume measures were correlated to Expanded Disability Status Scale (EDSS) scores at baseline and subsequent follow-up visits. RESULTS: Hispanic patients had a higher baseline median EDSS score (interquartile range [IQR], 2.0; [1.0-3.5]) compared to Caucasians (median [IQR], 1.0 [.0-2.0]) and an increased risk of requiring ambulatory assistance (hazard ratio [HR], 9.7; 95% confidence interval [CI], 2.8-32.5). Normalized thalamic volume was moderately associated with EDSS scores (rs   = -.42,  P < .001 in Hispanics; rs   = -.32, P  = .002 in Caucasians) and was the best predictor of sustained disability worsening in both racial groups in a time-to-event analysis. CONCLUSIONS: The confounding impact of race on quantitative brain volume measures may affect the interpretation of outcome measures in MS clinical trials.