Intracranial volumetric changes govern cerebrospinal fluid flow in the Aqueduct of Sylvius in healthy adults

Purpose: To characterize the intracranial volumetric changes that influence the cerebrospinal fluid (CSF) pulse in the Aqueduct of Sylvius (AoS). Materials and Methods: Neck MRI data were acquired from 12 healthy adults (8 female and 4 males; mean age=30.9 years), using a 1.5 Tesla scanner. The intracranial arterial, venous and CSF volumes changes, together with the aqueductal CSF (aCSF) volume, were estimated from flow rate data acquired at C2/C3 level and in the AoS. The correlations and temporal relationships among these volumes were computed. Results: The aCSF volumetric changes were strongly correlated (r = 0.967, p<0.001) with the changes in intracranial venous volume, whose peak occurred 7.0% of cardiac cycle (p = 0.023) before peak aCSF volume, but less correlated with the intracranial arterial and CSF volume changes (r=-0.664 and 0.676 respectively, p<0.001). The intracranial CSF volume change was correlated with the intracranial venous volume change (r=0.820, p<0.001), whose peak occurred slightly before (4.2% of CC, p=0.059). Conclusion: The aCSF pulse is strongly correlated with intracranial venous volume, with expansion of the cortical veins occurring prior to aCSF flow towards the third ventricle. Both caudal-cranial aCSF flow and venous blood retention occur when arterial blood volume is at a minimum

Cerebral hydrodynamics imaging (from physiology to pathology)

Le développement de séquences spécifiques sensibles au flux (PC) en imagerie par résonance magnétique (IRM) a permis de réaliser une étude non invasive des interactions hydrodynamiques entre les flux vasculaires et de liquide cérébro-spinal (LCS) intracrâniens. Grâce à un logiciel semi-automatique de traitement des images, nous avons analysé ces interactions dans différentes populations. L étude du système veineux chez 18 jeunes sujets sains a montré l hétérogénéité des débits, la latéralisation du drainage et le rôle du réseau accessoire extrajugulaire, ainsi que les pulsatilités différentes entre sinus et veines jugulaires. Des exemples de thromboses veineuses ont montré le rôle des veines dans la régulation de la pression intracrânienne. Cette technique a été utilisée pour appréhender la physiopathologie des pathologies neurodégénératives. Les effets du vieillissement physiologique sur les débits artériels, et sur la dynamique de circulation du LCS ont d abord été étudiés. L apport de la PC-IRM dans le diagnostic des hydrocéphalies obstructives par sténose de l aqueduc a été évalué chez 17 patients hydrocéphales, avec les conséquences sur le choix thérapeutique et le suivi. Dans le cadre des démences, la PC-IRM a permis de décrire les modifications de flux observées dans l Hydrocéphalie à Pression Normale, la Maladie d Alzheimer, et les états pré-démentiels (MCI), et de proposer des théories physiopathologiques ainsi que des aides au diagnostic différentiel entre ces états. Enfin, d autres applications cliniques possibles (syringomyélie, post-radiothérapie ou post-chirurgie) sont présentées afin d illustrer l intérêt clinique et scientifique de ces évaluations.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Timed up-and-go and 2-minute walk test in patients with multiple sclerosis with mild disability: reliability, responsiveness and link with perceived fatigue.

Mobility limitations are frequent in patients with multiple sclerosis (MS), and could already be present in patients with so-called mild neurological disability (Expanded Disability Status Scale≤4). Assessing mobility in these patients is therefore of paramount importance. Timed upand- go test (TUG) and 2-minute walk test (2MWT) are two clinically feasible tests which reliability and responsiveness are unknown among these patients. Whether fatigue, which is the number one symptom among these patients, is linked to these limitations remains unknown. To explore the intrarater reliability and minimal detectable change (MDC95), as an index of responsiveness, of TUG and 2MWT. To explore their link with perceived fatigue among patients with multiple sclerosis (MS). Cross-sectional observational study, including two measures. Two university hospital outpatient centers. Patients (N=63, 49 seen twice) with MS with mild disability (Expanded Disability Status Scale≤4). 2MWT and TUG were performed twice in one occasion and repeated 2 weeks later. Modified fatigue impact scale (MFIS) was used to assess fatigue. Intraclass coefficient correlations were calculated for immediate and 2-week reliability. MDC95 were computed. Correlations between mobility indices and fatigue were explored using Spearman's ρ. Mobility was impaired in comparison to normative values (2MWT: -4.9% from normative distance; TUG: +32% from normative time). The immediate reliability was excellent for both the 2MWT (ICC=0.98) and TUG (ICC=0.98). Reliability at 2 weeks was excellent for 2MWT (ICC=0.95) and very good for TUG (ICC=0.90). MDC95 were respectively 20m (2MWT) and 1.3s (TUG). Both measures were significantly weakly correlated to total MFIS (ρ=-0.37 and 0.39, respectively; p<0.01). The 2MWT and TUG are highly reliable and responsive in the assessment of respectively the walking capacity and general mobility of patients with MS with mild disability. Mobility impairments are linked to perceived fatigue among these patients. TUG and 2MWT are easy to administer and could be reliably used in so called mildly disabled patients with MS to assess mobility limitation

Effects of PR-Fampridine on gait pattern and patient-reported outcomes: A cross-over, randomized, placebo-controlled trial

Objective: The aim of this study was to explore the modification of gait parameters, in relation with patient-reported outcomes, following a treatment by prolonged release(PR)-Fampridine, among patients with MS. Methods: In this crossover, double-blind trial, patients with MS (EDSS ≤6) were first tested for responder status during a 4-week run-in period. Patients were considered responders if they improved their 25-foot timed walk test (25f-TWT) by at least 10% and improved their perceived walking capacity (Multiple Sclerosis Walking Scale-12 items (MSWS-12)). Responders were randomized to PR-fampridine (10mg, 2 times per day) or placebo for a 6-week period. After the end of this first period, they underwent a 2-week washout period before being given the other treatment. Participants were assessed before and after both treatments. Instrumented three-dimension gait analysis was used to assess gait impairments. Kinematic, kinetic and energetic parameters were recorder. phase. Six-minute walk test (6MWT) and 25f-TWT were used to assess walking capacity on long and short distances, respectively. Patient-reported outcomes were used to evaluate perceived fatigue (Modified Fatigue Impact Scale (MFIS)), perceived walking capacity (MSWS-12) and quality of life (SEP-59). For each variable, a repeated measures ANCOVA was applied, with the treatment being the explicative variable and the within-subject differences between baselines (prePR-fampridine and prePlacebo) being the covariate. Results: 24 patients were included (12 women; median EDSS 4.25 [4-5]; mean age 46±10 years; maximal walking speed 0.93±0.38m.s-1; baseline 6MWT: 295.7±126m). The only kinetic parameter significantly modified was external work (-0.039 J.kg-1.m-1, i.e. 9%, p=0.02). Regarding kinematic parameters, K4 of the dominant limb was significantly increased by the intervention (+5.3°; p=0.02). Step length was also statistically, but not clinically significantly, reduced in both sides (-1.7 cm; p=0.002). A trend toward an improvement was observed in the 6MWT (+17.6m [-2.5 m - +37.6 m], p=0.07). No statistically significant differences were found in other walking tests and patient-reported outcomes. Conclusions: PR-Fampridine increases knee flexion during swing phase and lowers external work. Whether these changes are related to clinically meaningful improvements in walking capacity and other functional parameters is unknown. The research was funded by BIOGE

Effects of prolonged-release fampridine on multiple sclerosis-related gait impairments. A crossover, double-blinded, placebo-controlled study

Background: People with multiple sclerosis have reduced walking speed and impaired gait pattern. Prolonged release-fampridine is a potassium channel blocker that improves nerve conduction in patients with multiple sclerosis, leading to walking benefits. Whether fampridine alters gait pattern is unknown. Methods: In this crossover, randomized controlled trial, patients with multiple sclerosis were tested for responder status during a 4-week run-in period. Patients were considered responders if they improved their 25-ft walk test by 10% and improved their perceived walking capacity. Responders were randomized to prolonged release- fampridine (10 mg b.i.d.) or placebo for a 6-week period. After a 2-week wash-out period, they were allo- cated to the other treatment for 6 weeks. Participants were assessed before and after both conditions. Three- dimensional gait analysis assessed kinematic, kinetic, mechanic and energetic variables while walking on a treadmill at comfortable speed. Six-minute walk test and 25-ft walk test were used to assess walking speed on middle and short-distances, respectively. Patient-reported outcome measures were also used. Repeated measures ANCOVAs were applied to assess the treatment effects. Findings: Out of 39 included patients, 24 responders (12 women; Expanded Disability Status Scale:4.25[4–5]; age:46 ± 10 years; maximal speed:0.93 ± 0.38 m⋅s− 1) were identified. Among them, prolonged release- fampridine reduced the external mechanical work (− 0.039 J⋅kg− 1⋅m− 1;p = 0.02), and improved knee flexion during swing phase (+5.3◦; p = 0.02). No differences were found in other walking tests and patient-reported outcomes, at group-level. Interpretation: Prolonged release-fampridine increases knee flexion during swing phase and lowers mechanical external work. Whether these changes are related to clinically meaningful improvements in walking capacity and other functional variables should be further investigated

Telecommunication and rehabilitation for patients with multiple sclerosis. Access and willingness to use: a cross-sectional study.

BACKGROUND: Telerehabilitation is a promising approach for patients with multiple sclerosis (MS), but uncertainties regarding patients' access and preferences remain. AIM: To investigate the access to telecommunication technologies and rehabilitation services of patients with MS, and their willingness to use these technologies for rehabilitation. DESIGN: Cross-sectional survey. SETTING: Outpatient neurological facility. POPULATION: Patients with MS. METHODS: Patients with MS attending consultations in the Neurology department were asked to fill in a paper questionnaire. This anonymous z was designed to gain information about needs and access to rehabilitation and telecommunication technologies, as well as interests and perspectives of telerehabilitation among these patients. Descriptive statistics, Chi-squared tests and logistic regressions were used to describe the sample and survey answers. RESULTS: Two hundred patients completed the questionnaire. Mean age was 44.41(±12.52) years. Seventy-one percent were women, and 49% were unemployed. Ninety-one percent of the patients regularly used internet and 73% used apps. Most patients were interested in using telecommunication technologies to receive a program of physical exercises (62%), for information and personalized advice about physical activity and MS (69%), and to communicate with caregivers (75%). Patients with EDSS>4 were less interested than patients with EDSS≤4 in communicating with the caregivers via apps (33% vs. 52%,Δ19%[CI-36%;-2%],P=0.04) but expressed greater interest in receiving information and personal advice about physical activity and MS via the internet (70% vs. 51%,Δ19%[CI+2%;+36%],P=0.03). One third of the patients was not interested in receiving telerehabilitation interventions (32%), notably patients with EDSS>4 and non-workers. CONCLUSIONS: Patients with MS are mainly interested in using telecommunication technologies for rehabilitation services, and most of these patients have access to the required technology. Being mildly disabled and having a professional activity are associated with a greater interest in telerehabilitation. In contrary, patients with moderate-to-severe disability and non-workers have reportedly less access and ease in using the required technologies. Clinical rehabilitation impact: Telerehabilitation is feasible and wished by patients with MS, specifically in patients with low EDSS scores and workers. Given the strong need for rehabilitation in more disabled patients, the barriers to its access, the lower access and ease of use of telecommunication technologies, a special effort is needed to facilitate their use in these patients

Assessing the mobility of patients suffering from multiple sclerosis with mild neurological disability: reliability and responsiveness of the 2-minute walk test and the timed up-and-go test

Introduction: Limitations of mobility are frequent and disabling in persons with multiple sclerosis (pwMS), even when neurological disability is ‘mild’ (Expanded Disability Status Score (EDSS) ≤4). It is noteworthy to use high-quality measurement tools to monitor disease progression, to guide its management and monitor the efficacy of treatments. The timed up-and-go test (TUG) and the 2-minute walk test (2MWT) are valid to assess functional mobility and walking capacity, respectively, and widely used among pwMS. However, among those with mild disability, their reliability and responsiveness are unknown. Purpose: To determine the immediate and middle-term reliability and minimal detectable change (MDC95), as an index of responsiveness, of TUG and 2MWT in pwMS with mild neurological disability. Method: Thirty-six ambulatory pwMS (mean age:46; median EDSS:2.5; 30 women) performed consecutively two trials of 2MWT and of TUG. Twenty-five of these patients were assessed a second time, two weeks later, to assess middle-term reliability. Results were compared to normative values. Intraclass correlation coefficients (ICC, two-way random model, absolute agreement) were used to assess reliability. Bland-Altman method was used to explore agreement between measures. MDC95 at two weeks was calculated. Results: Mobility was impaired, in comparison to normative values (2MWT: -7.5% from normative distance; TUG: +30% from normative time). The immediate reliability was excellent for the 2MWT (ICC=0.98) and TUG (ICC=0.96). The difference between the second and the first trial of the 2MWT, performed 5 minutes apart, was correlated with the EDSS score (ρ=-0.41, p=0.01). Reliability at 2 weeks was excellent for 2MWT (ICC=0.93) and very good for TUG (ICC=0.82). MDC95 were respectively 22m (2MWT) and 1.79s (TUG). Conclusions: 2MWT is highly reliable and responsive in assessing the walking capacity of pwMS, while TUG has acceptable properties to assess functional mobility among these patients. These tools can be broadly used in clinical practice and research while evaluating so-called mildly disabled pwMS

Effects of fampridine in people with multiple sclerosis: a systematic review and meta-analysis

Objectives: To summarize the evidence on the benefits of prolonged-release(PR)-fampridine among patients with MS. Data sources: A systematic search (last search January 2019) was conducted in Pubmed, Scopus (including EMBASE) and PsycINFO to identify trials that assessed PR-fampridine compared to placebo. A total of 705 articles were screened for inclusion. Review methods: Randomized controlled trials that assessed the effects of PR-fampridine versus placebo among patients with MS were selected by two independent reviewers. When appropriate, data was pooled using a random-effects model, and standardized mean differences (SMD) were computed. Quality of the studies was assessed by the Downs and Black checklist. PRISMA guidelines were followed. A standardized form was used to extract data from articles by two reviewers. All retrieved functional outcomes were classified according to the International Classification of Functioning, Disability and Health. Results: Twenty RCT involving 2616 patients met the eligibility criteria. Most studies were of good-to-excellent quality. PR-fampridine administration resulted in significant benefits on walking short (SMD: 1.25 (IC95% 0.65-1.81)) and middle distances (0.22 (0.06-0.38), as well as perceived walking capacity (0.64 (0.27-1.02)). A trend toward an improvement of muscle strength was observed (0.53 (-0.04-1.10)). No effect was observed on higher-level cognitive functions (-0.07 (-0.58 - 0.45)), and hand and arm use (0.16 (-0.33 – 0.64)). Individual studies reported effects on other outcomes across the ICF domains. Conclusions: Effects of PR-fampridine on walking short- and middle-distances, as well as perceived walking capacity are large and supported by strong evidence. Other benefits across the ICF are possible, but still not clear