Experiences of patients with poststroke spasticity throughout a botulinum toxin treatment cycle: Results from a prospective ethnographic study.

This study was conducted to capture the experience of patients with poststroke spasticity (PSS) throughout one botulinum neurotoxin A (BoNT-A) treatment cycle. The REBOT study (NCT03995524) was a prospective, observational ethnographic study conducted in France, Italy, the UK, and the USA. It combined a mixed-method ethnography (including semi-structured qualitative interviews within a week of a BoNT-A injection) with completion of a longitudinal quantitative patient-reported outcome questionnaire and sharing of video and images, both reported weekly over a 12-14-week period throughout the BoNT-A treatment cycle. The study recruited 30 adult patients with PSS who were receiving BoNT-A treatment. The most commonly used BoNT-A product was onabotulinumtoxinA (Botox®), which was administered to 21 patients (70%), whereas two patients (6.7%) received abobotulinumtoxinA (Dysport®) and seven patients (23.3%) did not specify the BoNT-A medication that they received. Patients reported a high, continuous burden of PSS, with spasms, sleeping difficulties, stiffness, and pain being the most commonly reported symptoms. In line with an observed waning effect of BoNT-A injections, spasticity symptoms initially were improved at Weeks 4-6 after injection but reemerged after 9-11 weeks. Treatment satisfaction levels decreased over the BoNT-A treatment cycle, as reflected by the worsening of symptoms and the need to self-medicate and consult a physician. The psychological impact of PSS was high. Patients acknowledged the benefits of BoNT-A treatment but wished for more individualized treatment plans with flexible dosing and injection intervals. Additionally, only 10% of patients reported that they had a trusting relationship with their physician and believed that their needs were considered by those managing their PSS. To our knowledge, this was the first ethnographic study in patients with PSS who were treated with BoNT-A. This ethnographic approach to patient surveys complements traditional research methods and allows improved identification of patients' unmet needs by capturing their weekly experience of treatment. The findings of this study confirm previous observations of the diminishing effectiveness of BoNT-A injections between treatment sessions, highlighting the need for agents with a longer duration of action and/or a more flexible treatment pattern that allows for more frequent injections.

The spasticity-related quality of life 6-dimensions instrument in upper-limb spasticity: Part I Development and responsiveness.

OBJECTIVE: To describe the development of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D) and its sensitivity to clinical change (responsiveness). DESIGN: Multicentre, prospective, longitudinal cohort study at 8 UK sites (NCT03442660). PATIENTS: Adults (n = 104) undergoing focal treatment of upper limb spasticity. METHODS: No condition-specific health-related quality of life tool is available for upper-limb spasticity of any aetiology. The SQoL-6D was developed to fulfil this need, designed to complement the Upper Limb Spasticity Index (which incorporates the Goal Attainment Scaling evaluation of upper limb spasticity [GASeous] tool) with targeted standardised measures. The 6 dimensions of the SQoL-6D (score range 0-4) map onto common treatment goal areas identified in upper-limb spasticity studies. A Total score (0-100) provides overall spasticity-related health status. To assess responsiveness, the SQoL-6D, Global Assessment of Benefit scale and "GASeous" were administered at enrolment and 8 weeks. RESULTS: Significant differences in mean SQoL-6D Total score change and effect sizes across patients rating "some benefit" (0.51) and "great benefit" (0.88) supported responsiveness. CONCLUSION: The SQoL-6D is a promising new measure of health status in upper limb spasticity, that enables systematic assessment of the impact of this condition in relation to patients' priority treatment goals. A psychometric evaluation of SQoL-6D is presented separately.

The spasticity-related quality of life 6-dimensions instrument in upper-limb spasticity: Part II A first psychometric evaluation.

OBJECTIVE: Psychometric evaluation of the Spasticity-related Quality of Life 6-Dimensions instrument (SQoL-6D). DESIGN: A clinimetric evaluation conducted in a multicentre, prospective, longitudinal cohort study at 8 UK sites. PATIENTS: Adult patients (n=104) undergoing focal treatment of upper-limb spasticity. METHODS: The SQoL-6D was administered in the clinic at enrolment and at 8 weeks, then 1-4 days later at home to assess test-retest reliability. RESULTS: The SQoL-6D demonstrated adequate construct validity and unidimensionality of the scale, allowing the calculation of a Total score. Cronbach's alpha (0.74) supported the internal consistency reliability, while the intraclass correlation coefficient supported test-retest reliability (0.82). Correlation coefficients with established instruments supported convergent validity, while significant differences between known-groups (of differing clinical severity) in SQoL-6D Total score confirmed its sensitivity to both cross-sectional and longitudinal differences. CONCLUSION: The SQoL-6D is a promising new measure to assess health status for patients with upper-limb spasticity of any aetiology. Further investigation and exploration of the allocation of weights to convert the SQoL-6D to a health-related quality of life utility index, are required.

Longitudinal goal attainment with integrated upper limb spasticity management including repeat injections of botulinum toxin A: Findings from the prospective, observational Upper Limb International Spasticity (ULIS-III) cohort study.

OBJECTIVE: To assess the longitudinal effects of integrated spasticity management incorporating repeated cycles of botulinum toxin A type A (BoNT-A) over 2 years. METHODS: The Upper Limb International Spasticity study was a prospective, observational, cohort study following adult patients over 2 years of integrated upper-limb spasticity management including repeat botulinum toxin (BoNT-A) treatment (any commercially-available product). RESULTS: A total of 1,004 participants from 14 countries were enrolled, of which 953 underwent ≥ 1 BoNT-A injection cycle (median 4 cycles) and had ≥ 1 goal attainment scaling assessment. Most participants (55.9-64.6% across cycles 1-6) saw a therapist after BoNT-A treatment; the most frequent therapy intervention was passive stretch (70.1-79.8% across cycles 1-6). Patients achieved their goals as expected over repeated cycles; mean cumulated goal attainment scaling T-score at 2 years was 49.5 (49.1, 49.9). Mean goal attainment scaling change scores of ≥ 10 were maintained across up to 7 cycles. Higher rates of goal achievement were seen for primary goals related to passive vs active function (86.6% vs 71.4% achievement). Standardized measures of spasticity, pain, involuntary movements, active and passive function improved significantly over the study. CONCLUSION: This large, international study provides evidence for benefit of repeated cycles of BoNT-A, over 2 years captured through person-centred goal attainment and standardized measures.

Assessing the effectiveness of upper-limb spasticity management using a structured approach to goal-setting and outcome measurement: First cycle results from the ULIS-III Study.

OBJECTIVE: To describe the utility of a structured approach to assessing effectiveness following injection with botulinum toxin-A alongside physical therapies, within the first cycle of the Upper Limb International Spasticity-III (ULIS-III) study. METHODS: ULIS-III (registered at clinicaltrials.gov as NCT02454803) is a large international, observation-al, longitudinal study of adults treated for upper-limb spasticity. It introduces novel methods for the structured evaluation of person-centred goal attainment alongside targeted standardized outcome measures: the Upper limb Spasticity Index, and the Upper Limb Spasticity Therapy Recording Schedule. RESULTS: A total of 953/1,004 enrolled patients (95%) completed cycle 1. Mean overall goal attainment scaling (GAS) T scores were 49.8 (95% confidence interval 49.2-50.3; 67.1% of patients met their primary goal, with highest achievement rates for goals related to involuntary movement, (75.6%) and range of movement (74.4%). Standardized measures of spasticity, pain, involuntary movements, active and passive function, all improved significantly over the treatment cycle. Overall, 59.7% of patients saw a therapist following botulinum toxin-A injection. Interventions varied, as expected, with the set treatment goals. After controlling for concomitant therapies using the upper limb spasticity therapy recording schedule, significant differences in injection intervals (p < 0.001) were seen between the commercially-available botulinum toxin-A agents. CONCLUSION: The results of this study confirm the utility of the Upper Limb Spasticity Index and Upper Limb Spasticity Therapy Recording Schedule as a structured approach to capturing goal-setting, therapy inputs and outcomes assessment.

Duration of Symptom Relief Between Injections for AbobotulinumtoxinA (Dysport®) in Spastic Paresis and Cervical Dystonia: Comparison of Evidence From Clinical Studies.

Background: Botulinum toxin-A is a well-established treatment for adult and pediatric spastic paresis and cervical dystonia. While guidelines and approved labels indicate that treatment should not occur more frequently than every 12 weeks, studies and real-world evidence show that the timing of symptom recurrence between treatments may vary. Methods: We report retreatment criteria and response duration (retreatment intervals) from four pivotal, double-blind, placebo-controlled studies with open-label extensions involving patients treated with abobotulinumtoxinA (aboBoNTA) for upper limb (NCT01313299) or lower limb (NCT01249404) spastic paresis in adults, lower limb spastic paresis in children (NCT01249417), and cervical dystonia in adults (NCT00257660). We review results in light of recently available preclinical data. Results: In spastic paresis, 24.0-36.9% of upper limb patients treated with aboBoNTA and 20.1-32.0% of lower limb patients did not require retreatment before 16 weeks. Moreover, 72.8-93.8% of aboBoNTA-treated pediatric patients with lower limb spastic paresis did not require retreatment before 16 weeks (17.7-54.0% did not require retreatment before 28 weeks). In aboBoNTA-treated patients with cervical dystonia, 72.6-81.5% did not require retreatment before 16 weeks. Conclusion: AboBoNTA, when dosed as recommended, offers symptom relief beyond 12 weeks to many patients with spastic paresis and cervical dystonia. From recently available preclinical research, the amount of active neurotoxin administered with aboBoNTA might be a factor in explaining this long duration of response.

Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity.

Background: Botulinum toxin-A (BoNT-A) injections are first-line treatment for adult spasticity. Prior patient surveys have reported that BoNT-A treatment improves quality of life but that symptoms usually recur before the next injection. We aimed to explore, in-depth, patient perceptions of the impact of spasticity and the waning of BoNT-A therapeutic effects. Methods: An internet-based survey was conducted through Carenity, an online patient community, from May to September 2019 in France, Germany, Italy, UK and USA. Eligible respondents were adult patients with spasticity due to stroke, traumatic brain injury (TBI) or spinal cord injury (SCI) who had ≥2 previous BoNT-A injections. Results: Two hundred and ten respondents (mean 47.2 years) met screening criteria and had their responses analyzed. Overall, 43% of respondents had spasticity due to stroke, 30% due to TBI and 27% due to SCI. The mean [95% CI] injection frequency for spasticity management was 3.6 [3.4-3.7] injections/year. Respondents described the time profile of their response to BoNT-A. The mean reported onset of therapeutic effect was 12.9 [12.1-13.7] days and the mean time to peak effect was 5.0 [4.7-5.4] weeks. Symptom re-emergence between injections was common (83%); the time from injection to symptom re-emergence was 89.4 [86.3-92.4] days. Muscle spasms usually re-emerge first (64%), followed by muscle stiffness or rigidity (40%), and limb pain (20%). Over half (52%) of respondents said they had lost their self-confidence, 46% experienced depression and 41% experienced a lack of sleep due to their spasticity symptoms in the past 12 months. Following a report of symptom re-emergence, the most common management approaches were to add adjunctive treatments (36%), increase the BoNT-A dose (28%), and wait for the next injection (26%). Seventy two percentage of respondents said they would like a longer lasting BoNT-A treatment. Conclusions: Patients with spasticity can expect a characteristic profile of BoNT-A effects, namely time lag to onset and peak effect followed by a gradual decline in the symptomatic benefits. Symptom re-emergence is common and has significant impact on quality of life. Greater patient/clinician awareness of this therapeutic profile should lead to better level of overall satisfaction with treatment, informed therapeutic discussions and treatment schedule planning.

Corrigendum: Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity.

[This corrects the article DOI: 10.3389/fneur.2020.00388.].

Human Leukocyte Antigen Genotype as a Marker of Multiple Sclerosis Prognosis.

OBJECTIVE: In a previous pilot monocentric study, we investigated the relation between human leukocyte antigen (HLA) genotype and multiple sclerosis (MS) disease progression over 2 years. HLA-A*02 allele was correlated with better outcomes, whereas HLA-B*07 and HLA-B*44 were correlated with worse outcomes. The objective of this extension study was to further investigate the possible association of HLA genotype with disease status and progression in MS as measured by sensitive and complex clinical and imaging parameters. METHODS: Hundred and forty-six MS patients underwent HLA typing. Over a 4-year period of follow-up, we performed three clinical and magnetic resonance imaging (MRI) assessments per patient, which respectively included Expanded Disability Status Scale, Multiple Sclerosis Severity Scale, Timed-25-Foot-Walk, 9-Hole Peg Test, Symbol Digit Modalities Test, Brief Visual Memory Test, California Verbal Learning Test-II, and whole-brain atrophy, fluid-attenuated inversion recovery (FLAIR) lesion volume change and number of new FLAIR lesions using icobrain. We then compared the clinical and MRI outcomes between predefined HLA patient groups. RESULTS: Results of this larger study with a longer follow-up are in line with what we have previously shown. HLA-A*02 allele is associated with potentially better MS outcomes, whereas HLA-B*07, HLA-B*44, HLA-B*08, and HLA-DQB1*06 with a potential negative effect. Results for HLA-DRB1*15 are inconclusive. CONCLUSION: In the era of MS treatment abundance, HLA genotype might serve as an early biomarker for MS outcomes to inform individualized treatment decisions.

Single-arm study to assess comprehensive infusion guidance for the prevention and management of the infusion associated reactions (IARs) in relapsing-remitting multiple sclerosis (RRMS) patients treated with alemtuzumab (EMERALD).

BACKGROUND: Alemtuzumab is a humanized IgG monoclonal antibody approved in more than 60 countries for patients with relapsing remitting multiple sclerosis (RRMS). In phase 2 and 3 clinical trials (CAMMS223 (NCT00050778), CARE-MS I (NCT00530348), and CARE-MS II (NCT00548405)), patients receiving alemtuzumab demonstrated significantly greater improvements on clinical and MRI outcomes versus SC IFNß-1a; mild to moderate infusion-associated reactions (IARs) were the most frequently reported adverse events (AEs) associated with alemtuzumab. EMERALD (NCT02205489) was a phase 4, multicenter, multinational, single-arm study designed to assess an algorithm for the prevention and management of IARs in RRMS patients treated with alemtuzumab. METHODS: Patients were treated with a study regimen of enhanced IAR prophylaxis relative to phase 2 and 3 studies. H1 and/or H2 antagonists or equivalent gastroprotection (proton pump inhibitors) were given 1 day before alemtuzumab infusion, 1 h prior to the infusion, and post-infusion. Methylprednisolone was given orally 1 day before infusion, 1 h prior to the infusion, and as needed post-infusion. Antipyretics were given 1 h before infusion and as needed post-infusion. Anti-emetics and normal saline were given as needed during and post-infusion. RESULTS: Of the 61 patients screened, 58 (95.1%) were enrolled into the study. Of the 58 patients who received the first infusion of Period 1, 57 (98.3%) completed the 5 days of Course 1. A total of 54 patients received the first infusion of Period 2 and 53 completed the 3-day course. All patients (n = 58) completed the Month 6 visit and 54 the Month 12 visit. 93.1% of patients had at least one IAR (91.4% in Period 1 and 81.5% in Period 2), the majority of which were grade 1 (69.1%) or grade 2 (28.0%). The three most common IARs of headache, pyrexia, and rash occurred in 48.8%, 40.7%, and 24.1% of patients during the first course and 14.8%, 17.2%, and 5.6% of patients during the second course, respectively. The majority of IARs occurred within 6 h after the start of alemtuzumab infusion, with a peak during the first 2 h. The types and overall incidence of IARs were consistent with phase 2 and 3 trials. Frequency and distribution of rash were reduced in the EMERALD study compared with previous clinical trials. Serious IARs occurred in 15.5%, a higher rate than reported in clinical trials of alemtuzumab. CONCLUSION: Although most alemtuzumab-treated patients experienced IARs as in previous controlled clinical studies, there was an improvement in the frequency and distribution of alemtuzumab-associated rash, which may have been associated with this study's prophylaxis regimen.

Cognitive Fatigue, Sleep and Cortical Activity in Multiple Sclerosis Disease. A Behavioral, Polysomnographic and Functional Near-Infrared Spectroscopy Investigation.

Patients with multiple sclerosis (MS) disease frequently experience fatigue as their most debilitating symptom. Fatigue in MS partially refers to a cognitive component, cognitive fatigue (CF), characterized by a faster and stronger than usual development of the subjective feeling of exhaustion that follows sustained cognitive demands. The feeling of CF might result from supplementary task-related brain activity following MS-related demyelination and neurodegeneration. Besides, CF in MS disease might also stem from disrupted sleep. The present study investigated the association between the triggering of CF, task-related brain activity and sleep features. In a counterbalance mixed design, 10 patients with MS and 11 healthy controls were exposed twice for 16 min to a CF-inducing dual working memory updating task (TloadDback) under low or high cognitive demands conditions, counterbalanced. Considering known inter-individual differences and potential cognitive deficits in MS, the maximal cognitive load of the task was individually adapted to each participant's own upper limits. During the experimental sessions, cortical brain activity was measured using near-infrared spectroscopy (NIRS) during the CF-induction task, and in a resting state immediately before and after. Ambulatory polysomnography recordings were obtained on the nights preceding experimental sessions. When cognitive load was individually adapted to their processing capabilities, patients with MS exhibited similar than healthy controls levels of subjectively perceived CF, evolution of performance during the task, and brain activity patterns. Linear mixed models indicate a negative association between oxygenation level changes in the dorsolateral prefrontal cortex (DLPFC) and the triggering of subjective CF in patients with MS only. Longer total sleep time was also associated with higher CF in MS patients. These results suggest that controlling for cognitive load between individuals with and without MS results in a similar task-related development of subjective CF. Besides comparable performance and cortical brain activity between groups, mixed model analyses suggest a possible association between CF, DLPFC activity and sleep duration in MS disease.

Improving fatigue in multiple sclerosis by smartphone-supported energy management: The MS TeleCoach feasibility study.

BACKGROUND: Fatigue is a frequently occurring, often disabling symptom in MS with no single effective treatment. In current fatigue management interventions, personalized, real-time follow-up is often lacking. The objective of the study is to assess the feasibility of the MS TeleCoach, a novel intervention offering telemonitoring of fatigue and telecoaching of physical activity and energy management in persons with MS (pwMS) over a 12-week period. The goal of the MS TeleCoach, conceived as a combination of monitoring, self-management and motivational messages, is to enhance levels of physical activity thereby improving fatigue in pwMS in an accessible and interactive way, reinforcing self-management of patients. METHODS: We conducted a prospective, open-label feasibility study of the MS TeleCoach in pwMS with Expanded Disability Status Scale ≤ 4 and moderate to severe fatigue as measured by the Fatigue Scale for Motor and Cognitive Functions (FSMC). Following a 2-week run-in period to assess the baseline activity level per patient, the target number of activity counts was gradually increased over the 12-week period through telecoaching. The primary efficacy outcome was change in FSMC total score from baseline to study end. A subset of patients was asked to fill in D-QUEST 2.0, a usability questionnaire, to evaluate the satisfaction with the MS TeleCoach device and the experienced service. RESULTS: Seventy-five patients were recruited from 16 centres in Belgium, of which 57 patients (76%) completed the study. FSMC total score (p = 0.009) and motor and cognitive subscores (p = 0.007 and p = 0.02 respectively) decreased from baseline to week 12, indicating an improvement in fatigue. One third of participants with severe fatigue changed to a lower FSMC category for both FSMC total score and subscores. The post-study evaluation of patient satisfaction showed that the intervention was well accepted and that patients were very satisfied with the quality of the professional services. CONCLUSION: Using MS TeleCoach as a self-management tool in pwMS suffering from mild disability and moderate to severe fatigue appeared to be feasible, both technically and from a content perspective. Its use was associated with improved fatigue levels in the participants who completed the study. The MS Telecoach seems to meet the need for a low-cost, accessible and interactive self-management tool in MS.

Correction to: Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus.

The article Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus, written by Lambert et al., was originally published electronically on the publisher's internet portal on 27 January 2018 without open access.

Management of immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab: a Belgian consensus.

Alemtuzumab (Lemtrada®) is a humanized monoclonal antibody indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis with active disease defined by clinical or imaging features. Alemtuzumab demonstrated superior efficacy over active comparator in both treatment naive patients and those with inadequate response to prior therapy. Alemtuzumab is associated with a consistent and manageable safety and tolerability profile. Treatment with alemtuzumab for multiple sclerosis increases the risk for autoimmune adverse events including immune thrombocytopenia (ITP). Complete blood counts with differential should be obtained prior to initiation of treatment and at monthly intervals thereafter for 48 months after the last infusion. After this period of time, testing should be performed based on clinical findings suggestive of ITP. If ITP onset is confirmed, appropriate medical intervention should be promptly initiated, including immediate referral to a specialist. This paper presents the consensus of Belgian multiple sclerosis specialists and hematologists to guide the treating physician with practical recommendations.

HLA genotype as a marker of multiple sclerosis prognosis: A pilot study.

OBJECTIVE: The identification of a biomarker with prognostic value is an unmet need in multiple sclerosis (MS). The objective of this study was to investigate a possible association of HLA genotype with disease status and progression in MS, based on comprehensive and sensitive clinical and magnetic resonance imaging (MRI) parameters to measure disease effects. METHOD: A total of 118 MS patients (79 females, 39 males) underwent HLA typing. Patient MS status was assessed at two time points in a 2-year interval, based on clinical scores (including EDSS, MSSS, T25FW, 9-HPT, SDMT, BVMT, CVLT-II) and MRI evaluations. Quantitative brain MRI values were obtained for whole brain atrophy, FLAIR lesion volume change and number of new lesions using MSmetrix. Predefined HLA patient groups were compared as of disease status and progression. Global assessment was achieved by an overall t-statistic and assessment per measurement by a Welch test and/or Mann Whitney U test. The effects of multiple covariates, including age, gender and disease duration as well as scan parameters, were also evaluated using a regression analysis. RESULTS: The HLA-A*02 allele was associated with better outcomes in terms of MSSS, EDSS and new lesion count (Welch test p-value<0.05). The HLA-B*07 and HLA-B*44 alleles showed a global negative effect on disease status, although none of the measurements reached significance (p-value<0.05). Results for the HLA-DRB1*15, HLA-DQB1*06 and HLA-B*08 alleles were inconclusive. The influence of the confounding variables on the statistical analysis was limited.

Human leucocyte antigen (HLA) class I and II typing in Belgian multiple sclerosis patients.

This is one of the first studies to compare the frequencies of different human leucocyte antigen (HLA) class I and II alleles and haplotype HLA-DRB1*15-DQB1*06 in a cohort of 119 patients with multiple sclerosis (MS) and a cohort of 124 healthy controls in Belgium. An association with MS was found for the HLA-DRB1*15 (odds ratio [OR] 2.60 [95% confidence interval (CI) 1.51-4.50]) and HLA-DQB1*06 (OR 1.97 [95% CI 1.18-3.29]) alleles, and for haplotype DRB1*15-DQB1*06 (OR 2.63 [95% CI 1.52-4.56]). The HLA-B*07 allele also tended to be more frequent in MS patients (OR 1.46 [95% CI 0.80-2.65]) and more frequent among MS patients with than in those without the HLA-DRB1*15 allele (26/54 [48.1%] versus 6/65 [9.2%]; p value <0.0001). Other alleles were underrepresented in MS patients, such as the HLA-DRB1*07 (OR 0.39 [95% CI 0.21-0.73]) and HLA-A*02 (OR 0.56 [95% CI 0.34-0.94]), showing a protective role against the disease. The HLA-B*44 (OR 0.58 [95% CI 0.31-1.09]) and HLA-DRB1*04 (OR 0.75 [95% CI 0.42-1.34]) alleles tended to be less frequent in MS patients. Altogether, the significant results observed in this population are in line with those from other countries and confirm that propensity to MS can be due to a complex presence of various HLA class I and class II alleles.

Quantifying brain volumes for Multiple Sclerosis patients follow-up in clinical practice - comparison of 1.5 and 3 Tesla magnetic resonance imaging.

INTRODUCTION: There is emerging evidence that brain atrophy is a part of the pathophysiology of Multiple Sclerosis (MS) and correlates with several clinical outcomes of the disease, both physical and cognitive. Consequently, brain atrophy is becoming an important parameter in patients' follow-up. Since in clinical practice both 1.5Tesla (T) and 3T magnetic resonance imaging (MRI) systems are used for MS patients follow-up, questions arise regarding compatibility and a possible need for standardization. METHODS: Therefore, in this study 18 MS patients were scanned on the same day on a 1.5T and a 3T scanner. For each scanner, a 3D T1 and a 3D FLAIR were acquired. As no atrophy is expected within 1 day, these datasets can be used to evaluate the median percentage error of the brain volume measurement for gray matter (GM) volume and parenchymal volume (PV) between 1.5T and 3T scanners. The results are obtained with MSmetrix, which is developed especially for use in the MS clinical care path, and compared to Siena (FSL), a widely used software for research purposes. RESULTS: The MSmetrix median percentage error of the brain volume measurement between a 1.5T and a 3T scanner is 0.52% for GM and 0.35% for PV. For Siena this error equals 2.99%. When data of the same scanner are compared, the error is in the order of 0.06-0.08% for both MSmetrix and Siena. CONCLUSIONS: MSmetrix appears robust on both the 1.5T and 3T systems and the measurement error becomes an order of magnitude higher between scanners with different field strength.

Immune-reconstitution Inflammatory Syndrome in Multiple Sclerosis Patients Treated With Natalizumab: A Series of 4 Cases.

PURPOSE: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Progressive multifocal leukoencephalopathy (PML) is a rare complication of NTZ treatment. In patients developing PML, NTZ cessation causes a reconstruction of cellular immunity, a rapid transition of cells through the blood-brain barrier, and significant inflammation in the central nervous system, leading to immune-reconstitution inflammatory syndrome (IRIS), with potentially poor outcomes. The occurrence of this syndrome is accelerated by plasmapheresis, the standard treatment for NTZ-PML, due to enhanced clearance of NTZ and thus rapid reconstitution of cellular immunity. IRIS can also occur after cessation of NTZ in the absence of PML. METHODS: We describe 4 patients who developed IRIS after NTZ cessation. FINDINGS: For the first patient, treatment was switched to fingolimod to avoid risk of developing PML. Despite plasmapheresis, corticosteroids, and other therapies, the outcome in this patient was fatal. For the 3 other patients, PML was detected early on magnetic resonance imaging, and IRIS after NTZ cessation was managed with a favorable outcome; 1 of these patients was managed without plasmapheresis or corticosteroid treatment. IMPLICATIONS: These cases demonstrate the need to consider and manage therapeutic strategies relative to the individual patient's risk for PML or IRIS. NTZ cessation to avoid PML risk can lead to severe IRIS without PML. On the other hand, if PML develops and is detected early, plasmapheresis may not be considered necessary and IRIS may be limited, with a favorable outcome. These 2 scenarios should be considered when managing NTZ MS patients.

Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program.

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.