Personalized Template-Based Step Detection From Inertial Measurement Units Signals in Multiple Sclerosis.

Background: Objective gait assessment is key for the follow-up of patients with progressive multiple sclerosis (pMS). Inertial measurement units (IMUs) provide reliable and yet easy quantitative gait assessment in routine clinical settings. However, to the best of our knowledge, no automated step-detection algorithm performs well in detecting severely altered pMS gait. Method: This article elaborates on a step-detection method based on personalized templates tested against a gold standard. Twenty-two individuals with pMS and 10 young healthy subjects (HSs) were instructed to walk on an electronic walkway wearing synchronized IMUs. Templates were derived from the IMU signals by using Initial and Final Contact times given by the walkway. These were used to detect steps from other gait trials of the same individual (intra-individual template-based detection, IITD) or another participant from the same group (pMS or HS) (intra-group template-based detection, IGTD). All participants were seen twice with a 6-month interval, with two measurements performed at each visit. Performance and accuracy metrics were computed, along with a similarity index (SId), which was computed as the mean distance between detected steps and their respective closest template. Results: For HS participants, both the IITD and the IGTD algorithms had precision and recall of 1.00 for detecting steps. For pMS participants, precision and recall ranged from 0.94 to 1.00 for IITD and 0.85 to 0.95 for IGTD depending on the level of disability. The SId was correlated with performance and the accuracy of the result. An SId threshold of 0.957 (IITD) and 0.963 (IGTD) could rule out decreased performance (F-measure ≤ 0.95), with negative predictive values of 0.99 and 0.96 with the IITD and IGTD algorithms. Also, the SId computed with the IITD and IGTD algorithms could distinguish individuals showing changes at 6-month follow-up. Conclusion: This personalized step-detection method has high performance for detecting steps in pMS individuals with severely altered gait. The algorithm can be self-evaluating with the SI, which gives a measure of the confidence the clinician can have in the detection. What is more, the SId can be used as a biomarker of change in disease severity occurring between the two measurement times.

New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study.

BACKGROUND: Radiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria. METHODS: Patients referred to our center for deterioration in cognitive complaint at least 6 months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded. RESULTS: Forty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53 Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30 Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL). CONCLUSIONS: RIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.

Glioblastoma stem-like cells secrete the pro-angiogenic VEGF-A factor in extracellular vesicles.

Glioblastoma multiforme (GBM) are mortifying brain tumours that contain a subpopulation of tumour cells with stem-like properties, termed glioblastoma stem-like cells (GSCs). GSCs largely contribute to tumour initiation, propagation and resistance to current anti-cancer therapies. GSCs are situated in perivascular niches, closely associated with brain microvascular endothelial cells, thereby involved in bidirectional molecular and cellular interactions. Moreover, extracellular vesicles are suspected to carry essential information that can adapt the microenvironment to the tumour's needs, including tumour-induced angiogenesis. In GBM, extracellular vesicles produced by differentiated tumour cells and GSCs were demonstrated to disseminate locally and at distance. Here, we report that the pro-angiogenic pro-permeability factor VEGF-A is carried in extracellular vesicles secreted from ex vivo cultured patient-derived GSCs. Of note, extracellular vesicle-derived VEGF-A contributes to the in vitro elevation of permeability and angiogenic potential in human brain endothelial cells. Indeed, VEGF-A silencing in GSCs compromised in vitro extracellular vesicle-mediated increase in permeability and angiogenesis. From a clinical standpoint, extracellular vesicles isolated from circulating blood of GBM patients present higher levels of VEGF-A, as compared to healthy donors. Overall, our results suggest that extracellular vesicle-harboured VEGF-A targets brain endothelial cells and might impact their ability to form new vessels. Thus, tumour-released EV cargo might emerge as an instrumental part of the tumour-induced angiogenesis and vascular permeability modus operandi in GBM.