Carmela Leone

Measuring the cost of cognitive-motor dual tasking during walking in multiple sclerosis:

Purposeful, safe locomotion requires higher-level cortical processes, to meet the real-life demands of walking while performing concurrent cognitive tasks (e.g. recalling a shopping list or attending to a conversation). The assessment of walking and a secondary cognitive task under these ‘dual tasking’ conditions may represent a more valid outcome measure in multiple sclerosis (MS), by examining the occurrence and magnitude of the cognitive-motor interference of walking. This topical review provides a state-of-the-art overview of research into dual-tasking during walking in persons with MS, based on 14 recent papers. Studies consistently demonstrate a slowing of ambulation under dual tasking, regardless of the cognitive task demand, the stage of the disease and the disability level. The reciprocal effect of walking on the cognitive tasks was rarely assessed. We present our main findings, highlight the different factors contributing to dual-task deficits, identify methodological shortcomings and offer recommendations for constructing dual-tasking paradigms useful in clinical practice and research.

Multiple Sclerosis and CCSVI: A Population-Based Case Control Study

Background Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS). Objective To evaluate the possible association between CCSVI and MS, using a population-based control design. Methods A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled. Results CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83–12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12–5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40–10.3; p = 0.4). Conclusions A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.

Cognitive-motor dual-task interference: a systematic review of neural correlates.

HIGHLIGHTSCMi refers to the simultaneous performance of a cognitive and a motor task as DT.CMi is assessed by various techniques able to measure the related brain activity.FMRI studies showed additive/over‐additive brain activity as multiple resources are needed.Specific loci have been identified, although they may depend on the single components. ABSTRACT Cognitive‐motor interference refers to dual‐tasking (DT) interference (DTi) occurring when the simultaneous performance of a cognitive and a motor task leads to a percentage change in one or both tasks. Several theories exist to explain DTi in humans: the capacity‐sharing, the bottleneck and the cross‐talk theories. Numerous studies investigating whether a specific brain locus is associated with cognitive‐motor DTi have been conducted, but not systematically reviewed. We aimed to review the evidences on brain activity associated with the cognitive‐motor DT, in order to better understand the neurological basis of the CMi. Results were reported according to the technique used to assess brain activity. Twenty‐three articles met the inclusion criteria. Out of them, nine studies used functional magnetic resonance imaging to show an additive, under‐additive, over‐ additive, or a mixed activation pattern of the brain. Seven studies used near‐infrared spectroscopy, and seven neurophysiological instruments. Yet a specific DT locus in the brain cannot be concluded from the overall current literature. Future studies are warranted to overcome the shortcomings identified.

Prevalence of Walking-Related Motor Fatigue in Persons With Multiple Sclerosis Decline in Walking Distance Induced by the 6-Minute Walk Test

Objective. To investigate the individual occurrence of walking-related motor fatigue in persons with multiple sclerosis (PwMS), according to disability level and disease phenotype. Study design. This was a cross-sectional, multinational study. Participants. They were 208 PwMS from 11 centers with Expanded Disability Status Scale (EDSS) scores up to 6.5. Methods. The percentage change in distance walked (distance walked index, DWI) was calculated between minute 6 and 1 (DWI6-1) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify participants into 4 subgroups: (1) DWI6-1[≥5%], (2) DWI6-1[5%; –5%], (3) DWI6-1[–5%; > –15%], and (4) DWI6-1[≤−15%]. The latter group was labeled as having walking-related motor fatigue. PwMS were stratified into 5 subgroups based on the EDSS (0-2.5, 3-4, 4.5-5.5, 6, 6.5) and 3 subgroups based on MS phenotype (relapsing remitting [RR], primary progressive [PP], and secondary progressive [SP]). Results. The DWI6-1 was ≥5% in 16 PwMS (7.7%), between 5% and −5% in 70 PwMS (33.6%), between −5% and −15% in 58 PwMS (24%), and ≤−15% in 64 PwMS (30.8%). The prevalence of walking-related motor fatigue (DWI6-1[≤−15%]) was significantly higher among the progressive phenotype (PP = 50% and SP = 39%; RR = 15.6%) and PwMS with higher disability level (EDSS 4.5-5.5 = 48.3%, 6 = 46.3% and 6.5 = 51.5%, compared with EDSS 0-2.5 = 7.8% and 3-4 = 16.7%; P < .05). Stepwise multiple regression analysis indicated that EDSS, but not MS phenotype, explained a significant part of the variance in DWI6-1 (R2 = 0.086; P < .001). Conclusion. More than one-third of PwMS showed walking-related motor fatigue during the 6MWT, with its prevalence greatest in more disabled persons (up to 51%) and in those with progressive MS phenotype (up to 50%). Identification of walking-related motor fatigue may lead to better-tailored interventions.

Treatment options of cognitive impairment in multiple sclerosis

Multiple sclerosis (MS) is a progressive disease of the CNS, characterized by the production of widespread lesions in the brain and spinal cord. Inflammatory demyelination has traditionally been seen as the main disease process in MS; however, axonal damage or loss is increasingly being documented to occur early in the disease. Cognitive deficits can occur independently of physical disability, which complicates their identification and recognition. More recently, cortical demyelination has been identified among possible causes of cognitive impairment in MS. Neuropsychological studies have consistently demonstrated that 40–65% of patients with MS experience cognitive dysfunction, particularly in recent memory, information processing speed, and sustained attention. Early detection of cognitive impairment is essential to enable therapeutic intervention to alleviate symptoms or prevent further cognitive decline, although how best to manage MS-related cognitive impairment is currently unclear. Treatment strategies for cognitive impairment in MS are still in their infancy. This article will summarize several pharmacological attempts to enhance cognitive performances in people with MS.

Oral drugs in multiple sclerosis therapy: an overview and a critical appraisal.

Multiple sclerosis (MS) is characterized by demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of MS resulted in the introduction of numerous effective drugs with diverse mechanisms of actions, routes of administration and benefit–risk profiles. New oral drugs recently approved for MS treatment has led to significant achievements in MS management. The oral route of administration promotes patient satisfaction and increases therapeutic compliance; but their introduction has raised concerns regarding safety and tolerability; and a thorough analysis of the benefit/risk ratio is required. This article reviews the mechanisms of action, safety and efficacy of the licensed and experimental oral drugs in MS. Moreover, we put into perspective the disease, drug and patient-related factors that should be taken into account when considering the appropriate oral drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

Can we define a rehabilitation strategy for cognitive impairment in progressive multiple sclerosis? A critical appraisal

Cognitive impairment (CI) has been shown to be severe in patients with progressive forms of multiple sclerosis (MS), and the most frequently impaired domains are sustained attention, information processing speed, memory, and executive functions. In contrast to relapsing forms of MS, where studies have shown favorable results from cognitive rehabilitation, there is a lack of data on cognitive rehabilitation in progressive forms of MS. A specific approach in assessing CI and in designing and administering rehabilitation training for patients with progressive forms of MS is needed.

Offspring Number Does Not Influence Reaching the Disability’s Milestones in Multiple Sclerosis: A Seven-Year Follow-Up Study

Objectives: data on pregnancy long-term effects on multiple sclerosis (MS) course are still controversial; whether experiencing more than one pregnancy exposes one to risk of the disability‘s accrual is still unknown. We investigated differences existing in terms of disability progression among women with MS (wwMS) who had one or more children after their MS onset. Methods: Monoparous and multiparous wwMS were enrolled from the Catania MS Center, Italy, in a monocenter retrospective study. A Cox proportional hazards model was used to examine the effect of the number of parities on time from MS disease onset to EDSS 4.0 and 6.0. The study protocol was approved by the local Ethical Committee. Results: during the seven years of observation, 32.1% and 23.2% of the monoparous group reached expanded disability disease status (EDSS) 4.0 and 6.0 respectively, compared to 13.3% and 3.3% of the multiparous group (p = 0.057 and p = 0.017; respectively). The Kaplan–Meier curve analysis showed no statistically-significant differences between the two groups in reaching the two milestones. The multiparous group showed a longer time to reach the EDSS 4.0 (3.5 vs. 2.6 years, log-rank 0.57, p = 0.45). The Cox regression analysis showed that the EDSS at the time of first pregnancy (Exp(B) 9.4, CI 4.5–19.7, p < 0.001) and the time from MS onset to first pregnancy (Exp(B) 0.96, CI = 0.93–0.98, p < 0.05) were significant predictors of reaching the EDSS 4.0, whereas a model including only the EDSS one year after the first pregnancy significantly predicted (Exp(B) value of 6.4, CI 2.6–15.4, p < 0.001) the reaching of EDSS 6.0. Conclusions: Our results suggest that experiencing more than one pregnancy could not convey a different clinical outcome in wwMS. Further research is needed to confirm our results.

Effectiveness of music-based interventions on motricity or cognitive functioning in neurological populations: a systematic review.

BACKGROUND Motor and cognitive symptoms are frequent in persons with neurological disorders and often require extensive long-term rehabilitation. Recently, a variety of music-based interventions have been introduced into neurological rehabilitation as training tools. EVIDENCE ACQUISITION This review aims to 1) describe and define music-based intervention modalities and content which are applied in experimental studies; and 2) describe the effects of these interventions on motor and/or cognitive symptoms in the neurological population. The databases PubMed and Web of Science were searched. Cited references of included articles where screened for potential inclusion. A systematic literature search up to 20th of June 2016 was conducted to include controlled trials and cohort studies that have used music-based interventions for ≥3 weeks in the neurological population (in- and outpatients) targeting motor and/or cognitive symptoms. No limitations to publication date was set. EVIDENCE SYNTHESISː Nineteen articles comprising thirteen randomized controlled trials (total participants Nexp=241, Nctrl=269), four controlled trials (Nexp=59, Nctrl=53) and two cohort studies (N.=27) were included. Fourteen studies were conducted in stroke, three in Parkinsons disease, and two in multiple sclerosis population. Modalities of music-based interventions were clustered into four groups: instrument-based, listening-based, rhythm-based, and multicomponent-based music interventions. Overall, studies consistently showed that music-based interventions had similar or larger effects than conventional rehabilitation on upper limb function (N.=16; fine motricity, hand and arm capacity, finger and hand tapping velocity/variability), mobility (N.=7; gait parameters), and cognition (N.=4; verbal memory and focused attention). CONCLUSIONSː Variety of modalities using music-based interventions has been identified and grouped into four clusters. Effects of interventions demonstrate an improvement in the domains assessed. Evidence is most available for improving motricity in stroke. More studies are warranted to investigate cognition as well as motor and cognition dysfunctions in combination. Instrument-based music interventions can improve fine motor dexterity and gross motor functions in stroke. Rhythm-based music interventions can improve gait parameters of velocity and cadence in stroke, Parkinsons disease and multiple sclerosis. Cognition in the domains of verbal memory and focused attention can improve after listening-based music interventions in stroke.

The Use of Immunosuppressant Therapy for Multiple Sclerosis in Italy: A Multicenter Retroprospective Study.

Introduction Immunosuppressive agents (ISA) have been used in multiple sclerosis (MS) for decades, frequently as off label licensed therapies. Given the new MS treatment landscape, what place do ISA have in combating MS? Methods We conducted a retrospective multicentre study to investigate the frequency of ISA prescription in 17 Italian MS centres, and to describe the clinical factors related to ISA use. Results Out of 6,447 MS patients, 2,034 (31.6%) were treated with ISA, with Azathioprine being the most frequently used ISA overall. MS patients treated with ISA alone were more frequently affected by the progressive course (both primary and secondary) of the disease (RRR 5.82, 95% CI 4.14–8.16, p<0.0001), had higher EDSS (RRR 3.69, 95% CI 2.61–5.21, p<0.0001), higher assignment age (RRR 1.04, 95% CI 1.03–1.06, p<0.0001) than patients treated with only disease modifying drugs (DMDs). Conclusions Progressive course, higher EDSS, higher assignment age were the strongest predictors of ISA prescription and use in our population.