Objective
To explore the use of digital biomarkers to distinguish healthy controls (HC) from subjects with a radiologically isolated syndrome (RIS).
Methods
We developed a smartphone application ...called MS Screen Test (MSST) to explore several dimensions of the neurological exam such as finger tapping speed, agility, hand synchronization, low contrast vision and cognition during a short evaluation. This app was tested on a cohort of healthy volunteers including a subset of subjects who underwent two evaluations on the same day to assess reproducibility. In a second step, the app was tested on a cohort of RIS subjects. Performances of RIS subjects were compared with age and genre-matched HC.
Results
HC underwent two consecutive evaluations on MSST. The analysis showed good reproducibility for all measures. Then 21 RIS subjects were compared to 32 matched HC. Compared to HC, we found that RIS subjects had a lower finger tapping speed on the dominant hand (5.6 versus 6.5 taps per second;
p
= 0.005), a longer inter hand interval during the hand synchronization task (14.4 versus 11.3 ms;
p
= 0.03) and significantly poorer scores on the low contrast vision and cognition tests.
Conclusion
MSST only requires a smartphone to obtain digital biomarkers relative to several dimensions of the neurological examination. Our results highlighted subtle differences between HC and RIS subjects. We plan to evaluate this tool in MS patients, which will allow us to get a much larger sample of subjects, to determine whether digital biomarkers can predict disease course.
We aimed to link macro- and microstructure measures of brain white matter obtained from diffusion MRI with effective connectivity measures based on a propagation of cortico-cortical evoked potentials ...induced with intrasurgical direct electrical stimulation. For this, we compared streamline lengths and log-transformed ratios of streamlines computed from presurgical diffusion-weighted images, and the delays and amplitudes of N1 peaks recorded intrasurgically with electrocorticography electrodes in a pilot study of 9 brain tumor patients. Our results showed positive correlation between these two modalities in the vicinity of the stimulation sites (Pearson coefficient 0.54±0.13 for N1 delays, and 0.47±0.23 for N1 amplitudes), which could correspond to the neural propagation via U-fibers. In addition, we reached high sensitivities (0.78±0.07) and very high specificities (0.93±0.03) in a binary variant of our comparison. Finally, we used the structural connectivity measures to predict the effective connectivity using a multiple linear regression model, and showed a significant role of brain microstructure-related indices in this relation.
Background:
There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS)
Objective:
The aim of this study was to compare the effectiveness between natalizumab ...(NTZ) and fingolimod (FTY) in active relapsing–remitting MS
Method:
Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity.
Results:
A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group (p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029).
Conclusion:
BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY.
Objective
Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the ...field of DLGG, we aimed to establish the status quo within specialized European centers.
Methods
An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery.
Results
A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI.
Conclusion
A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET.
Importance of the study
We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed “minimal core of imaging” in clinical routine will facilitate future cooperative studies.
The radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances ...lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS.
Patients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age-matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility-based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions.
180 participants (45 RIS, 45 MS, 90 non-MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non-MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non-MS than MS from non-MS (p = 0.837). When a 6-lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis.
This study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non-MS, with similar performances to those in MS.
Introduction
Natalizumab, a therapy for relapsing–remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, ...practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, despite the absence of a large-scale efficacy evaluation.
Methods
We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID), defined as a ≥ 12-month consecutive period of ≥ 11 natalizumab infusions/year in France. We compared the 12-month risk difference of remaining relapse-free (primary endpoint) between patients who switched to EID (≤ 9 natalizumab infusions) and those who remained on SID, with a noninferiority margin of − 11%. We used propensity score methods such as inverse probability treatment weighting (IPTW) and 1:1 propensity score matching (PSM). Secondary endpoints were annualized relapse rate, disease progression, and safety.
Results
Baseline characteristics were similar between patients receiving EID (
n
= 147) and SID (
n
= 156). The proportion of relapse-free patients 12 months postbaseline was 142/147 in the EID (96.6%) and 144/156 in the SID group (92.3%); risk difference (95% CI) 4.3% (− 1.3 to 9.8%);
p
< 0.001 for non-inferiority. There were no significant differences between relapse rates (0.043 vs. 0.083 per year, respectively;
p
= 0.14) or Expanded Disability Status Scale mean scores (2.43 vs. 2.72, respectively;
p
= 0.18); anti-JC virus index values were similar (
p
= 0.23); and no instances of PML were reported. The comparisons using IPTW (
n
= 306) and PSM (
n
= 204) were consistent.
Conclusion
These results support the pertinence of using an EID strategy for RRMS patients treated with natalizumab.
Clinical Trials
gov identifier (NCT04580381).
•We propose the quantified neurological examination (QNE) a new, automatic and linear method to rate the neurological examination in multiple sclerosis.•Our preliminary study suggests that QNE could ...have comparable performances with EDSS, the current gold standard for disability evaluation in MS in daily practice.•QNE scores were strongly correlated EDSS and modeteraly associated to MRI metricsAdditional investigations are undergoing to assess the sensitivity to change and inter rater agreement of the scale.
The Expanded Disability Status Scale (EDSS) is the gold standard for evaluating clinical disability in multiple sclerosis (MS) in daily practice. However, more precise clinical assessment tools are needed. We assessed a new, automated rating of the neurological examination obtained with a mobile application (Quantified Neurological Examination – QNE).
Consecutive MS patients were assessed for EDSS score and QNE application that calculates, from the description of the examination, a global score and subscores (qFSS) corresponding to the EDSS functional system scores (FSS). Brain MRI was analysed to obtain automatic measures of brain atrophy.
We performed 200 examinations and included 78 patients in the MRI analysis. The global QNE score was strongly correlated with the EDSS. qFSS was statistically different according to the corresponding FSS for each function, except for the visual FSS. EDSS was predominantly correlated to the pyramidal function of the lower limbs. QNE score and qFSS had at least equivalent correlation to MRI measures than EDSS, particularly regarding the gray matter and cortical volumes.
We propose an automated method to rate neurological disability in MS. While QNE strongly correlates with EDSS, it may allow a more precise way to monitor the evolution of disability.
Objective
We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5‐year risk for evolution from radiologically isolated ...syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10‐year, multinational, retrospectively identified RIS dataset.
Methods
RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models.
Results
Additional follow‐up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11–74 years), with a median clinical follow‐up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium‐enhanced lesions during follow‐up was also associated with the risk of a seminal event. The reason for MRI and gadolinium‐enhancing lesions at baseline did not influence the risk of a subsequent clinical event.
Interpretation
Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407–417.
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