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What you need to know: Disease-modifying therapies (DMTs) early in the course of active relapsing multiple sclerosis can prevent relapses, new brain and spinal cord lesions, and worsening neurological disability; Some DMTs are associated with potentially serious adverse reactions, and careful monitoring is required, usually through a specialist multiple sclerosis clinic; Newer DMTs have better short term outcomes than older DMTs, but there are insufficient data about their long term effectiveness and harms. A 32 year old woman with multiple sclerosis presented to her general practitioner with a five day history of numbness and weakness in the right leg. She felt well in herself and did not describe any symptoms to suggest an intercurrent infection. She had been taking weekly intramuscular injections of interferon beta-1a for the previous 18 months and reported flu-like symptoms that could last for up to 24 hours after each dose. She asked if there was a need to change her treatment and what alternatives were available.

Eight young children who displayed destructive behavior maintained, at least in part, by negative reinforcement received long‐term functional communication training (FCT). During FCT, the children completed a portion of a task and then touched a communication card attached to a microswitch to obtain brief breaks. Prior to and intermittently throughout FCT, extinction probes were conducted within a withdrawal design in which task completion, manding, and destructive behavior were placed on extinction to evaluate the relative persistence of appropriate and destructive behavior over the course of treatment. FCT continued until appropriate behavior persisted and destructive behavior failed to recur at baseline levels during extinction probes. The completion of FCT was followed by four challenges to the persistence of treatment effects conducted within mixed‐ or multiple‐schedule designs: (a) extended extinction sessions (from 5 to 15 min), (b) introduction of a novel task, (c) removal of the microswitch and communication card, and (d) a mixed schedule of reinforcement in which both appropriate and destructive behavior produced reinforcement. The results showed that although FCT often resulted in quick reductions in destructive behavior and increases in appropriate behavior, destructive behavior often recurred during the extinction probes conducted during the initial treatment. When the effects of treatment persisted during the extinction probes, the remaining challenges to treatment effects resulted in only mild to moderate disruptions in behavior. These results are consistent with the quantitative predictions of behavioral momentum theory and may provide an alternative definition of maintenance as constituting behavioral persistence.

Disease progression in multiple sclerosis (MS) is now known to affect many patients, even those not diagnosed with progressive subtypes. Progressive and neurodegenerative aspects of MS are poorly treated by currently available therapies. Research on new therapeutic options is needed to improve health outcomes in people with MS. This review highlights the potential for treatment using an engineered T cell receptor–regulatory T cell (TCR-Treg) therapy targeting the presynaptic protein beta-synuclein. Tregs respond to self-antigens presented on human leukocyte antigen (HLA) class II with anti-inflammatory and pro-neural healing effects, but this response is impaired in MS patients. Since the HLA-DRB1*15:01 allele is known to contribute to MS pathogenesis, a TCR specific to a known antigen presented on DRB1*15:01 can be transduced into Tregs to direct them to activate within the inflamed brain tissue. Beta-synuclein is released from neurons at a high level after neural damage, may be presented on HLA, enables homing of specific T cells to the grey matter, and is immunogenic in progressive MS patients. This review presents beta-synuclein as a disease-relevant antigen to target for therapeutic development.

Behavioral momentum theory provides a quantitative account of how reinforcers experienced within a discriminative stimulus context govern the persistence of behavior that occurs in that context. The theory suggests that all reinforcers obtained in the presence of a discriminative stimulus increase resistance to change, regardless of whether those reinforcers are contingent on the target behavior, are noncontingent, or are even contingent on an alternative behavior. In this paper, we describe the equations that constitute the theory and address their application to issues of particular importance in applied settings. The theory provides a framework within which to consider the effects of interventions such as extinction, noncontingent reinforcement, differential reinforcement of alternative behavior, and other phenomena (e.g., resurgence). Finally, the theory predicts some counterintuitive and potentially counterproductive effects of alternative reinforcement, and can serve as an integrative guide for intervention when its terms are identified with the relevant conditions of applied settings.

Vascular risk factors are associated with increased disease activity and disability progression in multiple sclerosis (MS). This has been studied mainly in cohorts with relapsing-remitting MS. However, the association between vascular comorbidities (VCM) and clinical disability in secondary progressive MS (SPMS) is less well studied. Our aim was to investigate the association between VCM, non-VCM, comorbidity burden and both physical and cognitive performance in SPMS. Longitudinal analysis of 445 patients from the MS secondary progressive multi-arm trial (MS-SMART)-a multi-arm multicentre phase-2b randomised placebo-controlled trial of three agents in SPMS (NCT01910259). VCM (hypertension and hyperlipidaemia) and non-VCM (asthma, hypothyroidism and osteoporosis) were recorded. A comorbidity score was also determined (0, 1, ≥ 2). Physical disability and processing speed were assessed at baseline, 48- and 96 weeks. Multiple linear regression and mixed models were used to investigate the cross-sectional and longitudinal relationships between baseline VCM, non-VCM, comorbidity score and clinical outcome measures. The cohort was predominantly female (67%), median Expanded Disability Status Scale (EDSS) 6.0. 13% and 9% had hypertension and hyperlipidaemia (VCM), respectively. 7%, 9% and 5% had asthma, hypothyroidism and osteoporosis (non-VCM), respectively. Co-morbidity counts were 0,63%; 1, 23% and with > = 2, 11%. In cross-sectional models, both hypertension (β = 0.36, 95% CI 0.18-0.54) and an increased comorbidity count (β = 0.47, 95% CI 0.28-0.67) were associated with higher EDSS scores. In longitudinal models, hyperlipidaemia (β = 0.22, 95% CI 0.02-0.42) and increased comorbidity count (β = 0.21, 95% CI 0.01-0.41) were associated with increased EDSS scores over 48/96 weeks. No associations were seen with the non-VCM. VCM and also increased comorbidity burden per se are associated with increased disability. Disability worsening over 96 weeks was most evident in those with hyperlipidaemia and increased comorbidity burden.

How two main treatments for late-onset multiple sclerosis compare in real life Multiple sclerosis (MS) is a disease where the immune system attacks the brain and spinal cord. When MS begins after the age of 50, it is called late-onset multiple sclerosis (LOMS). This form of MS can progress faster and respond differently to treatment compared to cases that start earlier in life. In this study, we compared two important groups of modern MS treatments: - Anti-CD20 therapies, which target specific immune cells, and - S1P receptor modulators, which prevent immune cells from reaching the brain. We analysed real-world data from an international MS registry called MSBase, including people with relapsing LOMS who had used one of these therapies for at least six months. We looked at how often relapses occurred, how disability changed over time, and whether disability increased independently of relapses. The results showed that, overall, both treatment types worked similarly in preventing relapses and disability worsening. However, in some patients—especially those younger than 55, with early disease and lower disability—anti-CD20 therapies appeared to have a small advantage. These findings suggest that both therapies are effective for most people with late-onset MS, but that starting anti-CD20 treatment early may be beneficial for selected patients. This information can help doctors personalise treatment plans for older adults living with MS.

Maintenance and generalization have been inconsistently defined in the behavior analytic literature. The term treatment relapse is used commonly in the medical and mental health literature to refer to the return of a condition that was previously considered successfully treated. Basic behavioral researchers have studied relapse related to behavioral momentum theory (BMT). The present authors discuss the differences in terminology and propose the field adopt the term treatment relapse when treatments are no longer effective or when their effects are not present in settings in which the treatment was not originally implemented. The implications BMT has for designing behavioral interventions to minimize or avoid treatment relapse are discussed along with a brief review of applied studies that demonstrate BMT may be useful for practitioners and applied researchers.

Behavioral momentum theory posits a paradoxical implication for behavioral interventions in clinical situations using differential reinforcement of alternative behavior (DRA): When alternative reinforcers are presented within the same context as the problem behavior, the added reinforcers may decrease the frequency of the behavior but also increase its persistence when the intervention ends. Providing alternative reinforcers in a setting that is distinctively different from that in which the target behavior occurs may avoid or reduce this increase in persistence. The present experiment compared behavioral persistence following standard DRA versus DRA in a different context that was available after refraining from target behavior (differential reinforcement of other behavior; DRO). We arranged a human laboratory model of treatment intervention using computer games and token reinforcement. Participants were five individuals with intellectual disabilities. Experimental phases included (a) an initial multiple-schedule baseline with token reinforcement for target behaviors A and B, (b) an intervention phase with alternative reinforcement using a conventional DRA procedure for A and a DRO-DRA procedure for B, and (c) an extinction phase with no interventions and no tokens. Response rates as proportion of baseline in the initial extinction phase were greater for A than for B for three of five participants. Four participants whose response rates remained relatively high during the extinction phase then received a second extinction-plus-distraction test with leisure items available. Response rates were greater for A than for B in three of four participants. The results indicate that DRO-DRA contingencies may contribute to reduced postintervention persistence of problem behavior.