Geographical Variation In Medication and Health Resource Use In Multiple Sclerosis.

BACKGROUND: Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care. METHODS: Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied. RESULTS: Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied. CONCLUSIONS: Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.

MR Susceptibility Separation for Quantifying Lesion Paramagnetic and Diamagnetic Evolution in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components. PURPOSE: To apply susceptibility separation (χ separation) to follow lesion evolution in MS with comparison to R2 */R2 ' /QSM. STUDY TYPE: Longitudinal, prospective. SUBJECTS: Twenty relapsing-remitting MS subjects (mean age: 42.5 ± 9.4 years, 13 females; mean years of symptoms: 4.3 ± 1.4 years). FIELD STRENGTH/SEQUENCE: Three-dimensional multiple echo gradient echo (QSM and R2 * mapping), two-dimensional dual echo fast spin echo (R2 mapping), T2 -weighted fluid attenuated inversion recovery, and T1-weighted magnetization prepared gradient echo sequences at 3 T. ASSESSMENT: Data were analyzed from two scans separated by a mean interval of 14.4 ± 2.0 months. White matter lesions on fluid-attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R2 * or separated into positive/negative components from χ separation. STATISTICAL TESTS: Two-sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between χ separation and R2 */R2 ' /QSM. Significant level: P < 0.005. RESULTS: A total of 183 lesions were quantified. Categorizing lesions into groups based on χ separation demonstrated significant annual changes in QSM//R2 */R2 ' . When lesions were grouped based on changes in QSM and R2 *, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility-sensitive MRI indices and χ separation. DATA CONCLUSION: Susceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R2 * and QSM alone. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Disease-modifying therapy use and health resource utilisation associated with multiple sclerosis over time: A retrospective cohort study from Alberta, Canada.

BACKGROUND: Estimating multiple sclerosis (MS) prevalence and incidence, and assessing the utilisation of disease-modifying therapies (DMTs) and healthcare resources over time is critical to understanding the evolution of disease burden and impacts of therapies upon the healthcare system. METHODS: A retrospective population-based study was used to determine MS prevalence and incidence (2003-2019), and describe utilisation of DMTs (2009-2019) and healthcare resources (1998-2019) among people living with MS (pwMS) using administrative data in Alberta. RESULTS: Prevalence increased from 259 (95% confidence interval [CI]: 253-265) to 310 (95% CI: 304, 315) cases per 100,000 population, and incidence decreased from 21.2 (95% CI: 19.6-22.8) to 12.7 (95% CI: 11.7-13.8) cases per 100,000 population. The proportion of pwMS who received ≥1 DMT dispensation increased (24% to 31% annually); use of older platform injection therapies decreased, and newer oral-based, induction, and highly-effective therapies increased. The proportion of pwMS who had at least one MS-related physician, ambulatory, or tertiary clinic visits increased, and emergency department visits and hospitalizations decreased. CONCLUSIONS: Alberta has one of the highest rates of MS globally. The proportion of pwMS who received DMTs and had outpatient visits increased, while acute care visits decreased over time. The landscape of MS care appears to be rapidly evolving in response to changes in disease burden and new highly-effective therapies.

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults.

Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where available) based approach to both the diagnosis and treatment of adult patients with autoimmune encephalitis. The guidelines were developed using a modified RAND process and included input from specialists in autoimmune neurology, neuropsychiatry and infectious diseases. These guidelines are targeted at front line clinicians and were created to provide a pragmatic and practical approach to managing such patients in the acute setting.

Predicting time to serologic diagnosis of AQP4+ NMOSD based on clinical factors and social determinants of health.

BACKGROUND: Early serologic diagnosis and initiation of targeted therapy are associated with better outcomes in aquaporin-4 IgG positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To determine predictors of time to serologic diagnosis of AQP4+ NMOSD. METHODS: In CANOPTICS, a multi-centre, Canadian cohort study of NMOSD, we retrospectively evaluated time from the first clinical attack to first positive AQP4-IgG serology. We used a multivariable negative binomial regression model to evaluate possible predictors of time to diagnosis. RESULTS: We identified 129 participants with AQP4+ NMOSD from 7 centres. Diagnostic delay of >1 month was observed in 82 (63.6 %). Asian compared to European (White) ethnicity (IRR:0.40, 95 % CI:0.21-0.78), female sex (IRR:0.56, 95 % CI:0.32-0.99), later calendar year (IRR:0.84, 95 % CI:0.81-0.86), and hospitalization for the first attack (IRR:0.35, 95 % CI:0.20-0.62) were associated with shorter times to serologic diagnosis. We did not observe any overall effect of Afro-Caribbean ethnicity, but in exploratory analyses, Afro-Caribbean individuals with low income had longer times to diagnosis. CONCLUSION: More than 60 % of patients with NMOSD experienced delays to AQP4-IgG serologic diagnosis in this cohort. Given evidence of more adverse long-term outcomes in Afro-Caribbean individuals with NMOSD, intersectional effects of ethnicity and social determinants of health merit further study.

Rituximab for Pediatric Central Nervous System Inflammatory Disorders in Alberta, Canada.

BACKGROUND: Early and effective treatment of central nervous system (CNS) inflammatory disorders is vital to reduce neurologic morbidity and improve long-term outcomes in affected children. Rituximab is a B-cell-depleting monoclonal antibody whose off-label use for these disorders is funded in the province of Alberta, Canada, by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric CNS inflammatory disorders in Alberta. METHODS: Rituximab applications for CNS inflammatory indications in patients <18 years of age were identified from the STEDT database between January 1, 2012, and December 31, 2019. Patient information was linked to other provincial datasets including the Discharge Abstract Database, Pharmaceutical Information Network, and Provincial Laboratory data. Analysis was descriptive. RESULTS: Fifty-one unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis without a specified antibody (n = 16, 31%). Most children were approved for a two-dose (n = 33, 66%) or four-dose (n = 16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets. CONCLUSION: The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring. Standardized protocols for the use of rituximab in these disorders and more robust outcome reporting will help better define the safety and efficacy of rituximab in this population.

Cancer risk, disease-modifying therapy, and age in multiple sclerosis: A retrospective population-based cohort study.

BACKGROUND: Long-term population-based safety studies are needed to investigate cancer outcomes in people with multiple sclerosis (MS) treated with modern disease-modifying therapy (DMT). OBJECTIVES: To investigate if exposure to DMT increases the risk of invasive cancer in MS. METHODS: We used population-based administrative health data from Alberta, Canada between 2008 and 2018. DMT exposure was defined in two ways: first as exposure to any DMT, and second by DMT type (modulating, sequestering, depleting). Study outcome was time to first diagnosis of invasive cancer. Cancer risk was compared to the general population using standardized incidence ratios (SIRs) and to the unexposed MS cases using hazard ratios (HRs). RESULTS: The analysis included 14,313 MS cases: 5,801 (40.5 %) were exposed to DMT. Median (interquartile range) follow-up was 8.4 (4.3, 10.4) years. Compared to the general population, there was no difference in cancer risk for the overall MS population (SIR: 0.94, 95 % confidence interval [CI]: 0.87, 1.02) or the DMT-exposed MS cases (SIR: 0.89; 95 % CI: 0.75, 1.05). Compared to unexposed MS cases, we found an interaction with age for exposure to any DMT (p = 0.001) and modulating DMT (p = 0.001), indicating that a difference in the risk of cancer associated with DMT depends on age. Cancer risk was not associated with exposure to sequestering DMT (HR: 1.28, 95 % CI: 0.78, 2.08) or depleting DMT (HR: 2.29, 95 % CI: 0.86, 6.14). CONCLUSIONS: Cancer risk for MS patients was similar to the general population. In the MS population, the age-dependent effect of DMT for cancer risk suggests a higher risk of cancer with age 62 or older and a protective effect at younger age. Further investigation is required to clarify whether the interaction between DMT exposure and age is a causal effect.

High-resolution diffusion tensor imaging and T2 mapping detect regional changes within the hippocampus in multiple sclerosis.

Hippocampus demyelinating lesions in multiple sclerosis (MS) have been frequently observed in ex vivo histopathological studies; however, they are difficult to image and quantify in vivo. Diffusion tensor imaging (DTI) and T2 mapping could potentially detect such regional in vivo changes if acquired with sufficient spatial resolution. The goal here was to evaluate whether there are focal hippocampal abnormalities in 43 MS patients (35 relapsing-remitting, eight secondary progressive) with and without cognitive impairment (CI) versus 43 controls using high-resolution 1 mm isotropic DTI, as well as complementary methods of T2-weighted and T2 mapping at 3 T. Abnormal hippocampus regions were identified voxel-by-voxel by using mean diffusivity (MD)/T2 thresholds and avoiding voxels attributed to cerebrospinal fluid. When compared with controls, averaged left/right whole hippocampus MD was higher in both MS groups, while lower fractional anisotropy (FA) and volume, and higher T2 relaxometry and T2-weighted signal values, were only significant in CI MS. The hippocampal MD and T2 images/maps were not uniformly affected and focal regions of elevated MD/T2 were evident in MS patients. Both CI and not CI MS groups showed greater proportional areas of the hippocampus with elevated MD, whereas only the CI group showed a greater proportional area of elevated T2 relaxation times or T2-weighted signal. Higher T2 relaxometry and T2-weighted signal values of elevated regions correlated with greater disability and whole hippocampus FA negatively correlated with physical fatigue. High-resolution hippocampus DTI and T2 mapping with less partial volume effects showed whole hippocampus abnormalities with regional elevations of MD/T2 in MS, which could be interpreted as potentially from demyelination, neuron loss, and/or inflammation, and which overall were more extensive in the hippocampus of patients with larger total brain lesion volumes and CI.

Good multiple sclerosis (MS) care and how to get there in Canada: Perspectives of Canadian healthcare providers working with persons with MS.

Objective: The literature that has examined healthcare access and needs of the multiple sclerosis (MS) population is limited. Currently, no research has engaged healthcare providers delivering services to this population to examine their perspectives on the provision of MS care in Canada. We aimed to summarize what good MS care should look like according to Canadian healthcare providers working with people with MS, and to identify the supports and resources required, within their care setting, to enable this standard of care. Methods: A qualitative descriptive approach was taken to analyze data from participants who responded to additional open-ended survey questions, within a larger "MS Models of Care Survey" targeting Canadian healthcare providers working with persons with MS. Results: Currently, a gap exists between what healthcare providers working with persons with MS believe MS care should encompass and what they are able to offer. Participants emphasized that their MS clinics are currently understaffed and patient-to-provider ratios are high, leaving very little time to address the array of healthcare concerns their patients present with. The healthcare providers overwhelmingly described that moving toward multidisciplinary team-based MS care that includes appropriate numbers of MS-trained neurologists, nurses, physiotherapists, occupational therapists, and mental health providers working within one location would be their prioritized approach to comprehensively managing MS care. This model of care enables all professionals to effectively coordinate care and use their time efficiently by only focusing on their area of expertise, all while meeting the needs of their patient in one setting, reducing wait-times and improving overall care. Conclusion: To meet the care needs of Canadians with MS, the healthcare system must consider standardizing and funding multidisciplinary team-based MS clinics, comparable to Stroke units, which continue to show favorable health outcomes after years of implementation.

Evaluating the impact of patient-reported outcome measures on depression and anxiety levels in people with multiple sclerosis: a study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease affecting multiple functional aspects of patients' lives. Depression and anxiety are common amongst persons with MS (PwMS). There has been an interest in utilizing patient-reported outcome measures (PROMs) to capture and systematically assess patient's perceptions of their MS experience in addition to other clinical measures, but PROMs are not usually collected in routine clinical practice. Therefore, this study aims to systematically incorporate periodic electronically administered PROMs into the care of PwMS to evaluate its effects on depression and anxiety. METHODS: A randomized controlled trial will be conducted with patients allocated 1:1 to either intervention or conservative treatment groups. Patients in the intervention group will complete PROMs at the start of the study and then every 6 months for 1 year, in addition to having their MS healthcare provider prompted to view their scores. The conservative treatment group will complete PROMs at the start of the study and again after 12 months, and their neurologist will not be able to view their scores. For both groups, pre-determined critical PROM scores will trigger an alert to the patient's MS provider. The difference in change in Hospital Anxiety and Depression Scale score between the intervention and conservative treatment groups at 12 months will be the primary outcome, along with difference in Consultation Satisfaction Questionnaire and CollaboRATE scores at 12 months, and proportion and type of healthcare provider intervention/alerts initiated by different PROMs as secondary outcomes. DISCUSSION: This study will determine the feasibility of utilizing PROMs on an interval basis and its effects on the psychological well-being of PwMS. Findings of this study will provide evidence on use of PROMs in future MS clinical practice. TRIAL REGISTRATION: This trial is registered at the National Institutes of Health United States National Library of Medicine, ClinicalTrials.gov NCT04979546 . Registered on July 28, 2021.

The Canadian Multiple Sclerosis Pregnancy Study: First-trimester miscarriages in women with multiple sclerosis.

BACKGROUND: There is increasing need for evidence-based data on reproduction for women with multiple sclerosis (MS). First-trimester (first 13 weeks) miscarriages are relatively common in the general population. It is therefore important to have information on the frequency with which this occurs in women with MS. METHODS: The Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS) is a prospective study on women with MS who are pregnant or actively trying to conceive. As far as we are aware, this is the first study on miscarriages for this population that takes into account each woman's entire pregnancy history (i.e. before and after the MS diagnosis as well as during enrollment in CANPREG-MS). RESULTS: There were 208 pregnancies during the study and 36 resulted in first-trimester miscarriage for a rate of 17.31%, within the expected range of 15%-20% for the general population. CONCLUSIONS: CANPREG-MS provides real world data that there does not appear to be an increase in first-trimester miscarriages for women with MS. This information will be helpful to women with MS and their healthcare providers.

"Building Your Neurology Acumen": A Flipped Classroom Approach for Internal Medicine Residents.

Globally, internal medicine (IM) residents often feel they lack the knowledge and skills to approach patients presenting with neurologic issues. We conducted a multiple method needs assessment to determine the feasibility of a novel neurology flipped classroom (FC) curriculum for internal medicine residents. Our primary findings include participants: (1) finding neurology a useful rotation; (2) feeling uncomfortable with the neurological examination; and (3) endorsing flipped classroom as a potential alternative but with significant barriers. Our findings elucidate upon the various extrinsic/intrinsic motivators for resident education and illustrate the need to re-examine the way in which neurology is being taught to off-service residents.

Inline dual-echo T2 quantification in brain using a fast mapping reconstruction technique.

T2 mapping from 2D proton density and T2-weighted images (PD-T2) using Bloch equation simulations can be time consuming and introduces a latency between image acquisition and T2 map production. A fast T2 mapping reconstruction method is investigated and compared with a previous modeling approach to reduce computation time and allow inline T2 maps on the MRI console. Brain PD-T2 images from five multiple sclerosis patients were used to compare T2 map reconstruction times between the new subtraction method and the Euclidean norm minimization technique. Bloch equation simulations were used to create the lookup table for decay curve matching in both cases. Agreement of the two techniques used Bland-Altman analysis for investigating individual subsets of data and all image points in the five volumes (meta-analysis). The subtraction method resulted in an average reduction of computation time for single slices from 134 s (minimization method) to 0.44 s. Comparing T2 values between the subtraction and minimization methods resulted in a confidence interval ranging from -0.06 to 0.06 ms (95% of values were within ± 0.06 ms between the techniques). Using identical reconstruction code based on the subtraction method, inline T2 maps were produced from PD-T2 images directly on the scanner console. The excellent agreement between the two methods permits the subtraction technique to be interchanged with the previous method, reducing computation time and allowing inline T2 map reconstruction based on Bloch simulations directly on the scanner.

The effect of nurse practitioner (NP-led) care on health-related quality of life in people with multiple sclerosis - a randomized trial.

BACKGROUND: Care for People with Multiple Sclerosis (PwMS) is increasingly complex, requiring innovations in care. Canada has high rates of MS; it is challenging for general neurologists to optimally care for PwMS with busy office practices. The aim of this study was to evaluate the effects of add-on Nurse Practitioner (NP)-led care for PwMS on depression and anxiety (Hospital Anxiety and Depression Scale, HADS), compared to usual care (community neurologist, family physician). METHODS: PwMS followed by community neurologists were randomized to add-on NP-led or Usual care for 6 months. Primary outcome was the change in HADS at 3 months. Secondary outcomes were HADS (6 months), EQ5D, MSIF, CAREQOL-MS, at 3 and 6 months, and Consultant Satisfaction Survey (6 months). RESULTS: We recruited 248 participants; 228 completed the trial (NP-led care arm n = 120, Usual care arm n = 108). There were no significant baseline differences between groups. Study subjects were highly educated (71.05%), working full-time (41.23%), living independently (68.86%), with mean age of 47.32 (11.09), mean EDSS 2.53 (SD 2.06), mean duration since MS diagnosis 12.18 years (SD 8.82) and 85% had relapsing remitting MS. Mean change in HADS depression (3 months) was: -0.41 (SD 2.81) NP-led care group vs 1.11 (2.98) Usual care group p = 0.001, sustained at 6 months; for anxiety, - 0.32 (2.73) NP-led care group vs 0.42 (2.82) Usual care group, p = 0.059. Other secondary outcomes were not significantly different. There was no difference in satisfaction of care in the NP-led care arm (63.83 (5.63)) vs Usual care (62.82 (5.45)), p = 0.194). CONCLUSION: Add-on NP-led care improved depression compared to usual neurologist care and 3 and 6 months in PwMS, and there was no difference in satisfaction with care. Further research is needed to explore how NPs could enrich care provided for PwMS in healthcare settings. TRIAL REGISTRATION: Retrospectively registered on clinicaltrials.gov ( ClinicalTrials.gov Identifier: NCT04388592 , 14/05/2020).

Evaluating occupational performance coaching to support fatigue management for people with multiple sclerosis: A feasibility study.

OBJECTIVE: To determine the feasibility of adding coaching sessions to a website (MS INFoRM) that supports self-directed fatigue management for people with multiple sclerosis (PwMS). DESIGN: Double-blind, parallel-group feasibility study. PARTICIPANTS AND SETTING: Twenty-six PwMS, who experienced severe fatigue (fatigue severity scale > 5.4), were recruited from participants who were ineligible for the main trial testing on the MS INFoRM website. INTERVENTION: Six 45-to-60-min sessions of one-on-one coaching plus access to the MS INFoRm website compared to two check-in phone calls plus access to the MS INFoRm website. Both study arms took place over 3 months. MAIN MEASURES: Feasibility parameters included proportion eligible of those screened; proportion consented; missing data; retention and adherence rates. Acceptability was explored through qualitative interviews. Secondary outcomes (self-efficacy and fatigue impact) were measured at baseline and post-intervention. RESULTS: 76 people were invited to participate in this add-on study. 40 were interested and screened: 32 were eligible, 26 consented, and were randomized (mean age: 48.5 yrs (SD: 8.7), mean disease duration: 11.5 yrs). Retention was 85% (22 out of 26). Coaching adherence was high (86% attended ⩾ 5 sessions). At 3 months, people in the intervention group showed more improvements in self-efficacy and fatigue impact compared to the comparison group, however, the difference was not statistically significant (p = 0.471 and p = 0.147, respectively). The intervention was well-received by the participants and there were no adverse events. CONCLUSION: Combining one-on-one coaching sessions along with web-based interventions is feasible and appreciated by the participants, and worth exploring further in a larger trial.

Models of Care in Multiple Sclerosis: A Survey of Canadian Health Providers.

Objective: Little work has evaluated integrated models of care in multiple sclerosis (MS) and the composition of MS care teams across Canada is largely unknown. We aimed to gather information regarding existing models of MS care across Canada, and to assess the perceptions of health care providers (HCPs) regarding the models of care required to fully meet the needs of the person with MS. Methods: We conducted an anonymous online survey targeting Canadian HCPs working in MS Clinics, and neurologists delivering MS care whether or not they were based in an MS Clinic. We queried the types of HCPs delivering care within formal MS Clinics, wait times for HCPs, the perceived importance of different types of HCPs for good quality care, assessments conducted, and whether clinic databases were used. We summarized survey responses using descriptive statistics. Results: Of the 716 HCPs to whom the survey was distributed, 100 (13.9%) people responded. Of the 100 respondents, 85 (85%) indicated that their clinical practice included people with MS and responded to specific questions about clinical care. The most common types of providers within MS Clinics with integrated models of care were neurologists and MS nurses. Of 23 responding MS Clinics, 10 (43.5%) indicated that there were not enough neurologists, and 16 (69.6%) indicated that there were not enough non-neurologist HCPs to provide adequate care. More than 50% of clinics reported wait times exceeding 3 months for physiatrists, physiotherapists, psychiatrists, psychologists, neuropsychologists and urologists; in some clinics wait times for these providers exceeded 1 year. Multiple disciplines were identified as important or very important for delivering good quality MS care. Over 90% of respondents thought it was important for neurologists, nurse practitioners, MS nurses and psychiatrists to be co-located within MS Clinics. Conclusion: Canadian HCPs viewed the ideal MS service as being multidisciplinary in nature and ideally integrated. Efforts are needed to improve timely access to specialized MS care in Canada, and to evaluate how outcomes are influenced by access to care.

Diffusion imaging of fornix and interconnected limbic deep grey matter is linked to cognitive impairment in multiple sclerosis.

Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS. The goal here was to evaluate DTI parameters and volumes of the fornix, as well as associated deep GM structures like the thalamus and hippocampus, with high-resolution fluid-attenuated inversion recovery (FLAIR)-DTI at 3T in 43 MS patients, with and without CI, versus 43 controls. The fornix, thalamus and hippocampus displayed atrophy and/or abnormal diffusion metrics, with the fornix showing the most extensive changes within the structures studied here, mainly in CI MS. The affected fornix volumes and diffusion metrics were associated with thalamic atrophy and atypical diffusion metrics in interconnected limbic GM, larger total lesion volume and global brain atrophy. Lower fractional anisotropy (FA) and higher mean and radial diffusivity in the fornix, lower hippocampus FA and lower thalamus volume were strongly correlated with CI in MS. Hippocampus FA and thalamus atrophy were negatively correlated with fatigue and longer time since MS symptoms onset, respectively. FLAIR-DTI and volumetric analyses provided methodologically superior evidence for microstructural abnormalities and extensive atrophy of the fornix and interconnected deep GM in MS that were associated with cognitive deficits.

Measuring the effects of nurse practitioner (NP)-led care on depression and anxiety levels in people with multiple sclerosis: a study protocol for a randomized controlled trial.

BACKGROUND: Canada has one of the highest rates of multiple sclerosis (MS) in the world. Treatments and supports for people with MS (PwMS) have become increasingly complex, requiring individualized and adaptive care. Specialized NPs provide advanced skills to those with complex medical conditions, with potential to enhance the health, functioning, and quality of life for PwMS. This study aims to determine the effect of a Nurse Practitioner (NP) on depression and anxiety levels in PwMS. METHODS: We will perform a parallel randomized controlled trial. PwMS who are followed by general private-practice neurologists will be randomly assigned to the intervention group (NP-led care) or the 'usual care' control group (general neurologist or family physician and registered nurse support). In the intervention group, the NP will assess and provide care to the MS patient and their caregiver at a baseline visit, with 3-month and 6-month follow-up visits. PwMS in the control group will receive usual care provided by their community neurologists or family physicians with the standard assistance provided by registered nurses experienced in MS care. The primary outcome will be the difference in change in the patient's anxiety and depression scores as measured by the validated Hospital Anxiety and Depression Scale (HADS) questionnaire at 3 months. Secondary outcomes will include difference in change in HADS at 6 months; Modified Fatigue Impact Scale scores (MSIF) at 3 and 6 months; EQ-5D scores at 3 and 6 months; caregiver health-related quality of life in MS measures (CAREQOL-MS) at 3 and 6 months; number of visits and phone calls to healthcare professionals recorded by patient, and satisfaction with NP-led care vs usual care measured by the validated Consultant Satisfaction Questionnaire. DISCUSSION: Findings from this study will contribute to exploring benefits of advanced nursing practitioner interventions for PwMS followed by general neurologists and family physicians in a community setting. It will provide evidence of the benefits of NP-led care for PwMS and offer an alternative healthcare resource for management of MS. TRIAL REGISTRATION: ClinicalTrials.gov Pro00069595 . Retrospectively registered on June 26, 2020. Protocol version: January 2017, version 1.