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IMPORTANCE: In 2017, the International Panel on Diagnosis of Multiple Sclerosis revised the McDonald 2010 criteria for the diagnosis of multiple sclerosis (MS). The new criteria are easier to apply and could lead to more and earlier diagnoses. It is important to validate these criteria globally for their accuracy in clinical practice. OBJECTIVE: To evaluate the diagnostic accuracy of the 2017 criteria vs the 2010 criteria in prediction of clinically definite MS in patients with a typical clinically isolated syndrome (CIS). DESIGN, SETTING AND PATIENTS: A total of 251 patients at Erasmus MC, Rotterdam, the Netherlands, in collaboration with several regional hospitals, fulfilled the inclusion criteria. Thirteen patients received another diagnosis early in the diagnostic process and therefore were excluded from the analyses. Nine patients with CIS declined to participate in the study. This left 229 patients who were included between March 2006 and August 2016 in this prospective CIS cohort. Patients underwent a baseline magnetic resonance imaging scan within 3 months after onset of symptoms and, if clinically required, a lumbar puncture was performed. Data were analyzed between December 2017 and January 2018. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, accuracy, and positive and negative predictive value were calculated after 1, 3, and 5 years for the 2017 vs the 2010 criteria. RESULTS: Among the 229 patients with CIS, 167 were women (73%), and the mean (SD) age was 33.5 (8.2) years. One hundred thirteen patients (49%) were diagnosed as having CDMS during a mean (SD) follow-up time of 65.3 (30.9) months. Sensitivity for the 2017 criteria was higher than for the 2010 criteria (68%; 95% CI, 57%-77% vs 36%; 95% CI, 27%-47%; P < .001), but specificity was lower (61%; 95% CI, 50%-71% vs 85%; 95% CI, 76%-92%; P < .001). Using the 2017 criteria, more MS diagnoses could be made at baseline (n = 97 [54%]; 95% CI, 47%-61% vs n = 46 [26%]; 95% CI, 20%-32%; P < .001). In the group with at least 5 years of follow-up, 33% of patients who were diagnosed as having MS using the 2017 criteria did not experience a second attack during follow-up vs 23% when using the 2010 criteria. CONCLUSIONS AND RELEVANCE: The 2017 revised McDonald criteria are associated with greater sensitivity but less specificity for a second attack than the previous 2010 criteria. The tradeoff is that it leads to a higher number of MS diagnoses in patients with a less active disease course.

Recent theories propose that movement observation is not a “passive mirror” of ongoing actions but might induce anticipatory activity when predictable movements are observed, e.g., because the action goal is known. Here we investigate this mechanism in a series of 3 experiments, by applying transcranial magnetic stimulation (TMS) to primary motor cortex (M1) while subjects observed either whole hand or precision grasping performed by an actor. We show that corticomotor excitability changes in a grip-specific manner but only once the grip can be decoded based on the observed kinematic cues (Exp. 1). By contrast, presenting informative contextual precues evokes anticipatory modulations in M1 already during the reach phase, i.e., well before the grip type could be observed, a finding in line with a predictive coding account (Exp. 2). Finally, we used paired-pulse (PP) TMS to show that ventral premotor cortex (PMv) facilitates grip-specific representations in M1 but only while grip formation is observed. These findings suggest that PMv and M1 interact temporarily and mainly when motor aspects of hand-object interactions are extracted from visual information. By contrast, no sustained input from PMv to M1 seems to be required to maintain action representations that are anticipated based on contextual information or once the grip is formed (Exp. 3).

When a stable memory is reactivated it becomes transiently labile and requires restabilization, a process known as reconsolidation. Animal studies have convincingly demonstrated that during reconsolidation memories are modifiable and can be erased when reactivation is followed by an interfering intervention. Few studies have been conducted in humans, however, and results are inconsistent regarding the extent to which a memory can be degraded. We used a motor sequence learning paradigm to show that the length of reactivation constitutes a crucial boundary condition determining whether human motor memories can be degraded. In our first experiment, we found that a short reactivation (less than 60 sec) renders the memory labile and susceptible to degradation through interference, while a longer reactivation does not. In our second experiment, we reproduce these results and show a significant linear relationship between the length of memory reactivation and the detrimental effect of the interfering task performed afterwards, i.e., the longer the reactivation, the smaller the memory loss due to interference. Our data suggest that reactivation via motor execution activates a time-dependent process that initially destabilizes the memory, which is then followed by restabilization during further practice.

To detect HuD‐specific T cells in patients with Hu‐antibody associated paraneoplastic neurological syndromes (Hu‐PNS), we used short‐term stimulation assays with HuD protein spanning peptide pools (PSPP) with purities of at least 70% and found reproducible false‐positive CD8+ T‐cell responses in three of 127 individuals (two healthy controls and one Hu‐PNS patient), which all shared HLA‐A*2402 and HLA‐B*1801. After testing the 15‐mer peptides of the HuD antigen separately, we discovered that the same three 15‐mers yielded the CD8+ T cell response in those three individuals. This highly unusual result could not be reproduced when using new batches of peptides with a higher level of purity (>82% and >95%). Therefore, we assumed this response was not directed against the HuD peptides and analyzed the HuD 15‐mers by Fourier transform ion cyclotron resonance (FT‐ICR) tandem mass spectrometry (MS/MS), which showed the presence of a cytomegalovirus (CMV)‐encoded peptide (AIAEESDEEEAIVAY) as a contaminant. The three responding individuals all were CMV‐seropositive and the contaminating peptide appeared to fit in the binding groove of HLA‐B*18. Our data reveal that synthetic PSPP may contain immunogenic contaminations which may cause false positive results in T‐cell stimulation assays. © 2008 International Society for Advancement of Cytometry

Current knowledge of Epstein–Barr virus (EBV)–specific T‐cell responses in the cerebrospinal fluid (CSF) of patients with EBV‐related lymphoproliferative disease (EBV‐LPD) in the central nervous system (CNS) is very limited. Here, we present two recipients of hematopoietic stem cell transplants with EBV‐LPD in the CNS. EBV‐specific CD8+T lymphocytes were detected in CSF and peripheral blood using major histocompatibility complex (MHC) class I multimers loaded with EBV‐derived peptides. The appearance of EBV‐specific CD8+T cells in CSF and blood correlated with neurological improvement and disappearance of EBV‐LPD. These observations suggest a role for EBV‐specific CD8+T cells in the control of EBV‐LPD in the CNS. Ann Neurol 2005;58:788–792