Brain health oriented care in multiple sclerosis : a critical role for specialst nurses?

Abstract: Multiple sclerosis (MS) is a chronic neuro-inflammatory and degenerative disease, with a prevalence of 1/1000 in Belgium. It causes a wide variety of disabling neurological symptoms and is associated with comorbidities such as depression and anxiety. Despite recent pharmaceutical advances, many persons with MS (pwMS) continue to suffer from hidden and burdensome symptoms such as fatigue or cognitive problems and often still develop progressive disability in the long term. These problems frequently remain inadequately addressed and, according to multiple stakeholders, require a multidisciplinary approach coordinated by an MS specialist nurse. Currently, access to and standardization of this type of care remains fragmented and limited by several hurdles. This dissertation tried to frame the current provision of healthcare for MS in Belgium and investigated the impact of an MS nurse and multidisciplinary care on health-related quality of life. Furthermore, the role of brain healthy behavior and its association with progression in MS was investigated, as nurses may play a crucial role in promoting brain health. The studies performed, show that there are structural differences between centers with and without an MS nurse or multidisciplinary team (MDT) regarding quality of care. However, the impact of an MS nurse or MDT remains inconclusive, mainly due to methodological limitations, variability of the MS nurses tasks and/or multidisciplinary team profile and heterogeneity of interventions offered. Future research should consist of longitudinal nurse-led and multidisciplinary interventions that focus on psychosocial variables such as self-efficacy, social support and coping. These studies should also take comorbidities and socio-economic background into account. Simultaneously, interventions promoting health behavior should be designed and investigated given that a brain healthy lifestyle may beneficially impact disease progression. Moreover, to substantiate the importance of a reimbursement for an MS nurse and MDT at a hospital network level, cost-effectiveness analyses need to be integrated in these interventional studies

Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis

Background: Cerebrospinal fluid (CSF) kappa free light chain (kappa FLC) measures gained increasing interest as diagnostic markers in multiple sclerosis (MS). However, the lack of studies comparing assay-dependent diagnostic cutoff values hinders their use in clinical practice. Additionally, the optimal kappa FLC parameter for identifying MS remains a subject of ongoing debate. Objectives: The aim of this study was to compare same-sample diagnostic accuracies of the kappa FLC index, kappa IgG index, CSF kappa FLC/IgG ratio, and isolated CSF kappa FLC (iCSF-kappa FLC) between two reference centers using different methods. Methods: Paired serum and CSF samples were analyzed for kappa FLC and albumin concentrations by Freelite (R)-Optilite (Sint-Jan Bruges hospital) and N Latex (R)-BNII (Ghent University hospital). Diagnostic performance to differentiate MS from controls was assessed using ROC curve analysis. Results: A total of 263 participants were included (MS, n = 80). Optimal diagnostic cutoff values for the kappa FLC index (Freelite (R)-Optilite: 7.7; N Latex (R)-BNII: 4.71), kappa IgG index (Freelite (R)-Optilite: 14.15, N Latex (R)-BNII: 12.19), and CSF kappa FLC/IgG ratio (Freelite (R)-Optilite: 2.27; N Latex (R)-BNII: 1.44) differed between the two methods. Sensitivities related to optimal cutoff values were 89.9% (Freelite (R)-Optilite) versus 94.6% (N Latex (R)-BNII) for the kappa FLC index, 91% (Freelite (R)-Optilite) versus 92.2% (N Latex (R)-BNII) for the kappa IgG index, and 81.3% (Freelite (R)-Optilite) versus 91.4% (N Latex (R)-BNII) for the CSF kappa FLC/IgG ratio. However, for iCSF-kappa FLC, optimal diagnostic cutoff values (0.36 mg/L) and related specificities (81.8%) were identical with a related diagnostic sensitivity of 89.9% for Freelite (R)-Optilite and 90.5% for N Latex (R)-BNII. The diagnostic performance of the kappa FLC index [area under the curve (AUC) Freelite (R)-Optilite: 0.924; N Latex (R)-BNII: 0.962] and kappa IgG index (AUC Freelite (R)-Optilite: 0.929; N Latex (R)-BNII: 0.961) was superior compared to CSF oligoclonal bands (AUC: 0.898, sensitivity: 83.8%, specificity: 95.9%). Conclusions: The kappa FLC index and the kappa IgG index seem to be excellent markers for identifying MS, irrespective of the method used for kappa FLC quantification. Based on the AUC, they appear to be the measures of choice. For all measures, optimal cutoff values differed between methods except for iCSF-kappa FLC. iCSF-kappa FLC might therefore serve as a method-independent, more cost-efficient, initial screening measure for MS. These findings are particularly relevant for clinical practice given the potential future implementation of intrathecal kappa FLC synthesis in MS diagnostic criteria and for future multicentre studies pooling data on kappa FLC measures

Alemtuzumab in multiple sclerosis : a retrospective analysis of occult hemorrhagic magnetic resonance imaging lesions and risk factors

Background and purpose Alemtuzumab, a monoclonal CD52 antibody, is a high-efficacy disease-modifying-therapy in relapsing-remitting multiple sclerosis (RRMS). Recently, intracerebral hemorrhage (ICH) was reported as a possible treatment-related adverse event. Arterial hypertension during infusion was suggested as a potential cause, although platelet or endothelial dysfunction may also contribute. This study aimed to screen for occult hemorrhagic cerebral lesions after alemtuzumab treatment and to further elucidate risk factors. Methods We included 30 RRMS patients who received alemtuzumab treatment at Ghent University Hospital or Sint-Jan Bruges Hospital. Retrospective data concerning vital signs, adverse effects and thrombocyte levels during treatment were collected. The occurrence of occult intracranial hemorrhagic lesions was assessed by magnetic resonance imaging with susceptibility-weighted imaging (SWI). Results The mean (standard deviation [SD]) systolic blood pressure (SBP) during the morning, afternoon and evening was 120 (3.38) mmHg during first administration and 114 (4.40) mmHg during second administration (N = 13). There was no significant increase in SBP when comparing morning, afternoon and evening per day, nor was there a significant difference in daily mean SBP between consecutive administration days. Thrombocyte count during treatment cycles ranged between 107 x 10(9)/L and 398 x 10(9)/L, with a mean (SD) absolute reduction of 59.3 x 10(9)/L (50.65) or a mean (SD) relative reduction of 25.0 (12.84)% (N = 20). No patient had ICH, nor did SWI show any cerebral microbleeds or other hemorrhagic lesions post-treatment (N = 23). Conclusions In our patient population, alemtuzumab treatment was not associated with arterial hypertension, ICH or occult microbleeds. Possible differences in administration regimen (ambulatory vs. in-hospital setting) and patient population (cardiovascular risk) might explain an increased risk in different populations

Lifestyle factors in multiple sclerosis disability progression and silent brain damage : a cross-sectional study

Objective: To determine the association between lifestyle risk factors with 1/ the Multiple Sclerosis Severity Score (MSSS) and 2/ ongoing subclinical brain damage in non-active MS patients on high-efficacy treatment. Methods: Cross-sectional study in persons with Multiple Sclerosis (PwMS) investigating lifestyle factors including cognitive reserve (CR), physical activity (PA), smoking status, alcohol use, dietary habits, body mass index (BMI), blood pressure (BP) and cholesterol ratio. Data were collected through validated questionnaires, clinical and laboratory examination. Serum Neurofilament light chain (sNfL) levels were used as a proxy for ongoing brain damage in a subgroup of persons with non-active MS on high-efficacy treatment. Multiple regression analysis (MRA) models explored the relationship between lifestyle factors with the MSSS score and sNfL. Results: 351 PwMS were included (43.04 +/- 11.77 years, 69.8% female). Higher CR and PA were associated with a lower MSSS; overweight or obesity and higher systolic BP with a higher MSSS. The MRA model explained 22.2% of the variance for MSSS (R-2.255, adjusted R-2.222). Higher BMI and BP were related to lower sNfL. Twenty-3% (R-2.279, adjusted R-2.230) of the variance was explained in the MRA model for sNfL. Conclusion: Our study suggests an association between a 'brain healthy lifestyle' with disability progression in MS. A cognitive and physical active lifestyle alongside a normal body weight and blood pressure may help to prevent future disability in MS. Longitudinal and interventional research is necessary to gain insight in the causal pathway of these risk factors in preventing disability progression in MS

Cognitive outcomes in Susac syndrome : a 2-year neuropsychological follow-up study

Background and purposeSusac syndrome (SuS) is a rare, autoimmune, neurological disease characterized by a clinical triad of branch retinal artery occlusion, sensorineural hearing loss and encephalopathy. Neuropsychological functioning in SuS is little researched and the prevalence, nature, and evolution over time of cognitive deficits in SuS remain unclear. This study aimed to better understand the long-term neuropsychological outcomes of patients with SuS.MethodsThirteen patients with SuS (mean [SD] age 39.5 [11.1] years) were enrolled at the Ghent University Hospital by their treating neurologist. The cognitive functioning and emotional well-being of each patient was evaluated by means of a thorough neuropsychological test battery at baseline and after 2 years. Follow-up testing after 2 years was performed in 11 patients (mean [SD] age 42.2 [11.5] years).ResultsPatients showed normal neuropsychological test results at a group level, both at baseline and follow-up testing. Significant improvements over time were found for information processing speed, verbal recognition, and semantic and phonological fluency. Individual test results showed interindividual variability at baseline, with most impairments being in attention, executive functioning and language, which improved after a 2-year period. In addition, patients reported significantly lower mental and physical well-being, both at baseline and follow-up testing.ConclusionsOur results suggest that neuropsychological dysfunction in SuS is limited at a group level and improves over time. Nonetheless, individual test results reveal interindividual variability, making cognitive screening essential. Furthermore, a high psycho-emotional burden of the disease was reported, for which screening and follow-up are necessary

Phenotyping vestibulocochlear manifestations in Susac syndrome : a cohort study

PurposeTo characterize vestibulocochlear involvement in patients with Susac syndrome (SuS), a rare immune-mediated endotheliopathy of cerebral, retinal and inner ear microvasculature causing a triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss.MethodsThe electronic patient files of 21 patients with SuS are reviewed for data on demography, clinical presentation, disease course and audiovestibular testing.ResultsAll 21 patients experienced some form of audiovestibular complaints during the disease course, with vertigo and instability being most frequently reported, followed by hearing loss, tinnitus and aural fullness. These audiovestibular symptoms did not always coincide. Fifteen patients had objectified predominant low- to midfrequency sensorineural hearing loss and 8 out of 18 patients showed abnormalities on vestibular testing, most frequently vestibular evoked myogenic potential-abnormalities, indicating otolith dysfunction. Treatment protocols consisted of uniformly extensive immunosuppressive therapy and hearing loss remained mostly mild.ConclusionAudiovestibular involvement is very common in patients with SuS. Characteristic findings include a "reverse-slope" configuration on audiological testing and otolith dysfunction on vestibular testing. Aggressive immunosuppression may prevent severe audiovestibular dysfunction. Symptoms as aural fullness and otolith dysfunction may indicate an underlying hydrops. Further investigations are necessary to elucidate the histopathological mechanisms underlying these preferentially involved cochleovestibular areas. Early recognition and treatment of SuS are important to stabilize or decrease disease activity and might also have beneficial effects on inner ear outcome.The submitted manuscript reports data derived from clinical observations in humansConsent for the research was provided by the Ethics Committee of Ghent University hospital (application number 2019/1443, registration date 31/12/2021, principal investigator Guy Laureys)

Multiple sclerosis multidisciplinary care : a national survey and lessons for the global community

Abstract: Background: Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives Methods: A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed Results: The PwMS survey comprised 916 respondents with a mean age of 46 +/- 12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR =3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment ( p =.015), spasticity ( p =.042) and gait treatment ( p =.035), but also more physiotherapy ( p =.004), driver 's license adjustment ( p <.001) and a higher employment rate ( p =.004). MDT access was associated with more frequent symptomatic bladder treatment ( p =.047), higher physiotherapy rate ( p <.001), higher work- ( p =.002), insurance- ( p <.001) and home support measures ( p =.019). PwMS without an available MDT more often indicated that MS care needs improvement ( p <.001). MSN 's ( n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists ( n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT 's should be organized at hospital-network leve

Multiple sclerosis multidisciplinary care : a national survey and lessons for the global community

Background Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives Methods A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed Results The PwMS survey comprised 916 respondents with a mean age of 46±12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR=3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment (p=.015), spasticity (p=.042) and gait treatment (p=.035), but also more physiotherapy (p=.004), driver's license adjustment (p<.001) and a higher employment rate (p=.004). MDT access was associated with more frequent symptomatic bladder treatment (p=.047), higher physiotherapy rate (p<.001), higher work- (p=.002), insurance- (p<.001) and home support measures (p=.019). PwMS without an available MDT more often indicated that MS care needs improvement (p<.001). MSN's (n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists (n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT's should be organized at hospital-network level Conclusion MDT and MSN availability may enhance medical and socio-economic support for PwMS. Guidelines, alignment and reimbursement are needed

Prediction of multiple sclerosis outcomes when switching to ocrelizumab

Background: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. Objective: To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. Methods: Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-beta/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1-2 months or 2-6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). Results: After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57-11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2-6 m compared to <1 m: HR = 9.57, 95% CI = 1.92-47.64, p = 0.006). Conclusion: The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch