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Background and Objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID., Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated., Results: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms., Discussion: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations., Competing Interests: Declaration of competing interest A.A. Toorop: nothing to disclose. M.H.J. Wessels: nothing to disclose. L.M.Y. Gelissen: nothing to disclose. E. Hoitsma: has accepted (speaker and congress) fees from Merck Serono, Biogen Idec, Roche, and Sanofi Genzyme. E.M.P.E. Zeinstra: reports advisory boards/consultancy fees for Merck, Novartis, Genzyme and Roche. L.C. van Rooij: nothing to disclose. C.E.P. van Munster: nothing to disclose. A. Vennegoor: nothing to disclose. J.P. Mostert: nothing to disclose. B.H.A. Wokke: nothing to disclose. N.F. Kalkers: nothing to disclose. E.L.J. Hoogervorst: nothing to disclose. J.J.J. van Eijk: reports honoraria for advisory boards and/or speakers fee from Merck Serono, Biogen Idec, Sanofi Genzyme, Roche and Novartis. C.M. Roosendaal: nothing to disclose. J.J. Kragt: nothing to disclose. M. Eurelings: nothing to disclose. J. Nielsen: nothing to disclose. J. van Genugten: nothing to disclose. L.G.F. Sinnige: nothing to disclose. M.E. Kloosterziel: nothing to disclose. E.P.J. Arnoldus: nothing to disclose. G.W. van Dijk: nothing to disclose. W.H. Bouvy: nothing to disclose. E.M.M. Strijbis: nothing to disclose. B.W. van Oosten: nothing to disclose. B.A. de Jong: nothing to disclose. B.I. Lissenberg-Witte: nothing to disclose. T. Rispens received funding for research from Genmab and consultancy fees from Novartis. B.M.J. Uitdehaag: reports research support and/or consultancy fees from Genzyme, Biogen Idec, Novartis, Teva Pharmaceutical Industries, Merck Serono, Roche, and Immunic Therapeutics. J. Killestein: received research grants for multicentre investigator initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials.gov Identifier: NCT05296161); received consulting fees for F. Hoffmann-La Roche Ltd., Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd., Biogen, Immunic, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); adjudication committee of MS clinical trial of Immunic (payments to institution only). Z.L.E. van Kempen: nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Perivascular spaces (PVS) are believed to be involved in brain waste disposal. PVS are associated with cerebral small vessel disease. At higher field strengths more PVS can be observed, challenging manual assessment. We developed a method to automatically detect and quantify PVS. A machine learning approach identified PVS in an automatically positioned ROI in the centrum semiovale (CSO), based on -resolution T2-weighted TSE scans. Next, 3D PVS tracking was performed in 50 subjects (mean age 62.9 years (range 27-78), 19 male), and quantitative measures were extracted. Maps of PVS density, length, and tortuosity were created. Manual PVS annotations were available to train and validate the automatic method. Good correlation was found between the automatic and manual PVS count: ICC (absolute/consistency) is 0.64/0.75, and Dice similarity coefficient (DSC) is 0.61. The automatic method counts fewer PVS than the manual count, because it ignores the smallest PVS (length <2 mm). For 20 subjects manual PVS annotations of a second observer were available. Compared with the correlation between the automatic and manual PVS, higher inter-observer ICC was observed (0.85/0.88), but DSC was lower (0.49 in 4 persons). Longer PVS are observed posterior in the CSO compared with anterior in the CSO. Higher PVS tortuosity are observed in the center of the CSO compared with the periphery of the CSO. Our fully automatic method can detect PVS in a 2D slab in the CSO, and extract quantitative PVS parameters by performing 3D tracking. This method enables automated quantitative analysis of PVS., (© 2022 The Author(s).)

Thus far, blood flow velocity measurements with MRI have only been feasible in large cerebral blood vessels. High-field-strength MRI may now permit velocity measurements in much smaller arteries. The aim of this proof of principle study was to measure the blood flow velocity and pulsatility of cerebral perforating arteries with 7-T MRI. A two-dimensional (2D), single-slice quantitative flow (Qflow) sequence was used to measure blood flow velocities during the cardiac cycle in perforating arteries in the basal ganglia (BG) and semioval centre (CSO), from which a mean normalised pulsatility index (PI) per region was calculated (n = 6 human subjects, aged 23-29 years). The precision of the measurements was determined by repeated imaging and performance of a Bland-Altman analysis, and confounding effects of partial volume and noise on the measurements were simulated. The median number of arteries included was 14 in CSO and 19 in BG. In CSO, the average velocity per volunteer was in the range 0.5-1.0 cm/s and PI was 0.24-0.39. In BG, the average velocity was in the range 3.9-5.1 cm/s and PI was 0.51-0.62. Between repeated scans, the precision of the average, maximum and minimum velocity per vessel decreased with the size of the arteries, and was relatively low in CSO and BG compared with the M1 segment of the middle cerebral artery. The precision of PI per region was comparable with that of M1. The simulations proved that velocities can be measured in vessels with a diameter of more than 80 µm, but are underestimated as a result of partial volume effects, whilst pulsatility is overestimated. Blood flow velocity and pulsatility in cerebral perforating arteries have been measured directly in vivo for the first time, with moderate to good precision. This may be an interesting metric for the study of haemodynamic changes in aging and cerebral small vessel disease. © 2015 The Authors NMR in Biomedicine Published by John Wiley & Sons Ltd., (© 2015 The Authors. NMR in Biomedicine Published by John Wiley & Sons Ltd.)

Memory problems and changes in hippocampal structures after chronic ecstasy use are well described in the literature. Cognitive problems after incidental ecstasy use are rare, and the few patients described in case reports returned to their normal cognitive level after a relative short period. FV is a 39-year-old man who used an ecstasy tablet in 2005. This resulted in severe confusion for a few days. The confusion was followed by persistent memory complaints and difficulties orientating in new surroundings. An extensive neuropsychological examination 7 years after the ecstasy use revealed a severe memory disorder. Furthermore, his performance on a virtual reality test of navigation showed serious problems navigating in new surroundings. In comparison with matched control subjects (Bayesian approach for single case studies) his scores were significantly impaired on several subtasks of the navigation test. On a magnetic resonance imaging (MRI) scan of the brain bilateral hippocampal atrophy and sclerosis were visible, comparable to previous MRI studies describing hippocampal damage following ecstasy ingestion. This case report describes persistent memory and navigation disorders after sporadic ecstasy use, supported by structural brain abnormalities seen on the MRI scan. These findings revive the debate on whether sporadic ecstasy use can cause persistent cognitive deficits.

The detection of abnormal intensities in brain images caused by the presence of pathologies is currently under great scrutiny. Selecting appropriate models for pathological data is of critical importance for an unbiased and biologically plausible model fit, which in itself enables a better understanding of the underlying data and biological processes. Besides, it impacts on one's ability to extract pathologically meaningful imaging biomarkers. With this aim in mind, this work proposes a fully unsupervised hierarchical model selection framework for neuroimaging data which permits the stratification of different types of abnormal image atterns without prior knowledge about the subject's pathological status.

Objectives: We examined whether patients with cerebral microbleeds on MRI, who started and continued antithrombotic medication for years, have an increased risk of symptomatic intracerebral haemorrhage (ICH)., Design: Prospective cohort study., Settings: Multicentre outpatient clinics in the Netherlands., Participants: We followed 397 patients with newly diagnosed transient ischaemic attack (TIA) or minor ischaemic stroke receiving anticoagulants or antiplatelet drugs. 58% were men. The mean age was 65.3 years. 395 (99%) patients were white Europeans. MRI including a T2*-weighted gradient echo was performed within 3 months after start of medication. 48 (12%) patients had one or more microbleeds. They were followed every 6 months by telephone for a mean of 3.8 years., Primary and Secondary Outcome Measures: Primary outcome was a symptomatic ICH. Secondary outcome were all strokes, ischaemic stroke, myocardial infarct, death from all vascular causes, death from non-vascular causes and death from all causes., Results: Five patients (1%) suffered from a symptomatic ICH. One ICH occurred in a patient with microbleeds at baseline (adjusted HR 2.6, 95% CI 0.3 to 27). The incidence of all strokes during follow-up was higher in patients with than without microbleeds (adjusted HR 2.3, 95% CI 1.0 to 5.3), with a dose-response relationship. The incidences of ischaemic stroke, vascular death, non-vascular death and death of all causes were higher in patients with microbleeds, but not statistically significant., Conclusions: In our cohort of patients using antithrombotic drugs after a TIA or minor ischaemic stroke, we found that microbleeds on MRI are associated with an increased risk of future stroke in general, but we did not find an increased risk of symptomatic ICH.