The T25FW and T100MW displayed subtle differences of reproducibility, variability, and correlation with MWD favoring the T100MW. The maximum walking speed of MS patients may be poorly estimated by the T25FW since MS patients were shown to walk faster over a longer distance.

These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs.

Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role of MR scanning has not been investigated but holds promise since MR detection is highly sensitive for PML lesions. The authors report a case of presymptomatic PML of the posterior fossa detected by MR scans. Immediate suspension of natalizumab and plasma exchanges resulted in a rapid decline of natalizumab serum concentration. Intravenous steroids started together with plasma exchanges followed by an oral tapering course were used to minimise the immune reconstitution inflammatory syndrome. No symptoms (beyond mild headache) developed, and the repeat PCR for JC Virus (JCV) DNA detection performed 10 weeks later was negative. This case suggests that: (1) periodic brain MR scans may detect signs of presymptomatic PML in MS patients treated with natalizumab, (2) corticosteroid management of inflammatory reaction may contribute to optimal control of the immune reconstitution inflammatory syndrome routinely seen with natalizumab-associated PML and (3) early radiological detection of PML can have an excellent outcome even in a clinically critical region and despite prior immunosuppressant exposure. The potential benefit of regular MR scanning just using the T2/FLAIR modalities could be further investigated in order to detect early natalizumab-associated PML, leading to benign outcomes.

Background and rationaleMotor fatigue and ambulation impairment are prominent clinical features of people with multiple sclerosis (pMS). We hypothesized that a multimodal and comparative assessment of walking speed on short and long distance would allow a better delineation and quantification of gait fatigability in pMS. Our objectives were to compare 4 walking paradigms: the timed 25-foot walk (T25FW), a corrected version of the T25FW with dynamic start (T25FW+), the timed 100-meter walk (T100MW) and the timed 500-meter walk (T500MW).MethodsThirty controls and 81 pMS performed the 4 walking tests in a single study visit.ResultsThe 4 walking tests were performed with a slower WS in pMS compared to controls even in subgroups with minimal disability. The finishing speed of the last 100-meter of the T500MW was the slowest measurable WS whereas the T25FW+ provided the fastest measurable WS. The ratio between such slowest and fastest WS (Deceleration Index, DI) was significantly lower only in pMS with EDSS 4.0–6.0, a pyramidal or cerebellar functional system score reaching 3 or a maximum reported walking distance ≤4000 m.ConclusionThe motor fatigue which triggers gait deceleration over a sustained effort in pMS can be measured by the WS ratio between performances on a very short distance and the finishing pace on a longer more demanding task. The absolute walking speed is abnormal early in MS whatever the distance of effort when patients are unaware of ambulation impairment. In contrast, the DI-measured ambulation fatigability appears to take place later in the disease course.

THE EARLIER, THE SMALLER, THE BETTER FOR NATALIZUMAB-ASSOCIATED PML: IN MRI VIGILANCE VERITAS?Natalizumab-associated progressive multifocal leukoencephalopathy (N-PML) in multiple sclerosis (MS) is due to CNS infection by the opportunistic JC virus (JCV). As of December 2011, 193 confirmed cases of N-PML have been observed, giving rise to an overall risk of approximately 0.202%. 1 N-PML pathogenesis remains partially elusive although risk factors have now been clearly delineated.2 In patients with prior JCV infection detected by serum anti-JCV antibodies, 3 duration of therapy and prior use of immunosuppressants (IS) increase the risk of N-PML. The clinical outcome of patients with MS who developed N-PML was highly variable, ranging from asymptomatic case 4 to varying degrees of neurologic disability or even death.5 It was also observed in real-life setting that the earlier N-PML was diagnosed and treated, the better was the clinical outcome.5 Clinical vigilance is now considered as the established cornerstone of PML risk-management algorithm. 2Here we present early MRI features of 4 out of 8 N-PML cases, which were observed in WalloniaBrussels and Northern France in more than 4 years of postmarketing utilization of natalizumab for both regions. We are not aware of the specific context and outcome of the 4 other N-PML cases, which were diagnosed and treated in other centers. The reported cases emphasize that 1) N-PML can have a long presymptomatic course while still being clearly detectable with MRI, 2) N-PML can have a benign outcome provided it is diagnosed and treated early, 3) a clinically symptomatic N-PML may be a further advanced infection with a poorer prognosis, and 4) periodic brain MRI scans, particularly in high-risk situations, are likely to provide earlier detection of N-PML 4 and better outcomes. Written informed consent was obtained from all 4 patients.Case discussion. We describe in the figure the clinico-radiologic features of 4 N-PML cases in which early preclinical MRI signs were captured. Case 1 was a left cerebellar peduncle lesion 4 (Liège, Belgium). Cases 2, 3 (Lille, France), and 4 (Brussels, Belgium) were left occipital, left posterior parietal, and right anterior frontal lesions, respectively. Case 4 emphasizes how slow and long can be the preclinical phase of N-PML and to what extent the size of the lesion at diagnosis is indicative of the duration of preclinical infection. The early MRI signs of supratentorial cases 2, 3, and 4 were all located in the cortical/juxtacortical white matter. Consistent with previous data, the Expanded Disability Status Scale status, the size of the MRI lesion, and the age of the patient at the time of diagnosis may correlate with the clinical outcome. 4 In cases 2, 3, and 4, the emergence of N-PML symptoms was concurrent with the development of T1 hypointensity (dark) within the lesion due to immune reconstitution inflammatory syndrome (IRIS) occurrence in cases 2 and 3 (not shown) and at the time of a late-stage clinical diagnosis in case 4 ( figure).Th...

In the September issue of the Annals of Neurology, Schweikert et al 1 reported the occurrence of a primary central nervous system lymphoma (PCNSL) in a patient with multiple sclerosis (MS) who was under natalizumab treatment, and accompanying editorials questioned the possible causal role of this immunotherapy. We recently encountered another case with overlapping features.Our 40-year-old patient had a 20-year history of tumefactive MS fulfilling current diagnostic criteria, with no prior immunotherapy. He was admitted with complaints of blurred vision, headaches, and attention disorders. Brain magnetic resonance imaging (MRI) showed enhancing (not shown) and This article was published online on 16 FEB 2011. An error was subsequently identified. This notice is included to indicate that the SGML and PDF has been corrected.

No abstract

Background: No clinical test is currently available and validated to measure the maximum walking speed (WS) of multiple sclerosis (MS) patients. Since the Timed 25-Foot Walk Test (T25FW) is performed with a static start, it takes a significant proportion of the distance for MS patients to reach their maximum pace. Objectives: In order to capture the maximum WS and to quantify the relative impact of the accelerating phase during the first meters, we compared the classical T25FW with a modified version (T25FW + ) allowing a dynamic start after a 3 meters run-up. Methods: Sixty-four MS patients and 30 healthy subjects performed successively the T25FW and the T25FW + . Results: The T25FW + was performed faster than the T25FW for the vast majority of MS and healthy subjects. In the MS population, the mean relative gain of speed due to the dynamic start on T25FW + was independent from the EDSS and from the level of ambulation impairment. Compared to healthy subjects, the relative difference between dynamic versus static start was more important in the MS population even in patients devoid of apparent gait impairment according to the T25FW. Conclusion: The T25FW + allows a more accurate measurement of the maximum WS of MS patients, which is a prerequisite to reliably evaluate deceleration over longer distance tests. Indirect arguments suggest that the time to reach the maximum WS may be partially influenced by the cognitive impairment status. The maximum WS and the capacity of MS patients to accelerate on a specific distance may be independently regulated and assessed separately in clinical trials and rehabilitation programs.