User appraisal of a booklet for advance care planning in multiple sclerosis: a multicenter, qualitative Italian study.

OBJECTIVES: Implementation of advance care planning (ACP) in people with progressive multiple sclerosis (PwPMS) is limited. We aimed to involve users (PwPMS, significant others, and healthcare professionals involved in PwPMS care) in the evaluation and refinement of a booklet to be used during the ACP conversations. METHODS: This qualitative study consisted of cognitive interviews with PwPMS and significant others and a focus group with healthcare professionals from three Italian centers. We analyzed the interviews using the framework method and the focus group using thematic analysis. RESULTS: We interviewed 10 PwPMS (3 women; median age 54 years; median Expanded Disability Status Scale score 6.0) and three significant others (2 women; 2 spouses and one daughter). The analysis yielded three themes: booklet comprehensibility and clarity, content acceptability and emotional impact, and suggestions for improvement. Twelve healthcare professionals (7 neurologists, 3 psychologists, one nurse, and one physiotherapist) participated in the focus group, whose analysis identified two themes: booklet's content importance and clarity and challenges to ACP implementation. Based on analysis results, we revised the booklet (text, layout, and pictures) and held a second-round interviews with two PwPMS and one significant other. The interviewees agreed on the revisions but reaffirmed their difficulty in dealing with the topic and the need for a physician when using the booklet. CONCLUSIONS: Appraisal of the booklet was instrumental in improving its acceptability and understandability before using it in the ConCure-SM feasibility trial. Furthermore, our data reveal a lack of familiarity with ACP practice in the Italian context.

Applying multidimensional computerized adaptive testing to the MSQOL-54: a simulation study.

BACKGROUND: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is one of the most commonly-used MS-specific health-related quality of life (HRQOL) measures. It is a multidimensional, MS-specific HRQOL inventory, which includes the generic SF-36 core items, supplemented with 18 MS-targeted items. Availability of an adaptive short version providing immediate item scoring may improve instrument usability and validity. However, multidimensional computerized adaptive testing (MCAT) has not been previously applied to MSQOL-54 items. We thus aimed to apply MCAT to the MSQOL-54 and assess its performance. METHODS: Responses from a large international sample of 3669 MS patients were assessed. We calibrated 52 (of the 54) items using bifactor graded response model (10 group factors and one general HRQOL factor). Then, eight simulations were run with different termination criteria: standard errors (SE) for the general factor and group factors set to different values, and change in factor estimates from one item to the next set at < 0.01 for both the general and the group factors. Performance of the MCAT was assessed by the number of administered items, root mean square difference (RMSD), and correlation. RESULTS: Eight items were removed due to local dependency. The simulation with SE set to 0.32 (general factor), and no SE thresholds (group factors) provided satisfactory performance: the median number of administered items was 24, RMSD was 0.32, and correlation was 0.94. CONCLUSIONS: Compared to the full-length MSQOL-54, the simulated MCAT required fewer items without losing precision for the general HRQOL factor. Further work is needed to add/integrate/revise MSQOL-54 items in order to make the calibration and MCAT performance efficient also on group factors, so that the MCAT version may be used in clinical practice and research.

Viability of a MSQOL-54 general health-related quality of life score using bifactor model.

BACKGROUND: MSQOL-54 is a multidimensional, widely-used, health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). Findings from the validation study suggested that the two MSQOL-54 composite scores are correlated. Given this correlation, it could be assumed that a unique total score of HRQOL may be calculated, with the advantage to provide key stakeholders with a single overall HRQOL score. We aimed to assess how well the bifactor model could account for the MSQOL-54 structure, in order to verify whether a total HRQOL score can be calculated. METHODS: A large international database (3669 MS patients) was used. By means of confirmatory factor analysis, we estimated a bifactor model in which every item loads onto both a general factor and a group factor. Fit of the bifactor model was compared to that of single and two second-order factor models by means of Akaike information and Bayesian information criteria reduction. Reliability of the total and subscale scores was evaluated with Mc Donald's coefficients (omega, and omega hierarchical). RESULTS: The bifactor model outperformed the two second-order factor models in all the statistics. All items loaded satisfactorily (≥ 0.40) on the general HRQOL factor, except the sexual function items. Omega coefficients for total score were very satisfactory (0.98 and 0.87). Omega hierarchical for subscales ranged between 0.22 to 0.57, except for the sexual function (0.70). CONCLUSIONS: The bifactor model is particularly useful when it is intended to acknowledge multidimensionality and at the same time take account of a single general construct, as the HRQOL related to MS. The total raw score can be used as an estimate of the general HRQOL latent score.

The Dysphagia in Multiple Sclerosis Questionnaire Correlates with Fiber-Optic Endoscopic Examination for Detecting Swallowing Deficits in MS.

Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Assessing for the presence of dysphagia in subjects with MS represents a challenge for neurologists in clinical practice. The aim of the present study was to verify the relationship between DYMUS scores, a patient-reported scale, and objective symptoms using the Dysphagia Outcome Severity Score (DOSS), based on fiber-optic endoscopy. Data were collected in a multicenter study. Two hundred and fifteen MS patients were enrolled, irrespective of self-reported dysphagia. DOSS revealed dysphagia in 122 subjects (56.7%). Compared with non-dysphagic subjects, the presence of dysphagia was related to more severe disability, longer disease duration, and a progressive form of the disease. A DYMUS score of 0 strongly correlated with a DOSS of 6 (sensitivity 100%) while DYMUS score of > 2 correlated with a DOSS < 7 (specificity 82%) of the self-reported scale. The DYMUS questionnaire can be a useful clinical tool for red-flagging patients who should undergo objective testing and referral to a otorhinolaryngologist.

Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing-remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated. METHODS: To address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the induced signaling pathways and functional properties. RESULTS: We found that macrophages, microglia, and CD4 T lymphocytes were the cells expressing the highest levels of IL-9 in the MS brain. Of the immune cells circulating in the blood, monocytes/macrophages were the most responsive to IL-9. We validated the expression of IL-9R by macrophages/microglia in post-mortem brain sections of MS patients. IL-9 induced activation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 and reduced the expression of activation markers, such as CD45, CD14, CD68, and CD11b in inflammatory macrophages stimulated in vitro with lipopolysaccharide and interferon (IFN)-γ. Similarly, in situ the number of activated CD68+ macrophages was significantly reduced in areas with high levels of IL-9. Moreover, in the same conditions, IL-9 increased the secretion of the anti-inflammatory cytokine, transforming growth factor (TGF)-ß. CONCLUSIONS: These results reveal a new cytokine expressed in the CNS, with a role in the context of MS. We have demonstrated that IL-9 and its receptor are both expressed in CNS. Moreover, we found that IL-9 decreases the activation state and promotes the anti-inflammatory properties of human macrophages. This mechanism may contribute to the beneficial effects of IL-9 that are observed in MS, and may be therapeutically potentiated by modulating IL-9 expression in MS.

Cerebellar Intermittent Theta-Burst Stimulation Combined with Vestibular Rehabilitation Improves Gait and Balance in Patients with Multiple Sclerosis: a Preliminary Double-Blind Randomized Controlled Trial.

Difficulties in gait and balance disorders are among the most common mobility limitations in multiple sclerosis (MS), mainly due to a damage of cerebellar circuits. Moreover, the cerebellum plays a critical role in promoting new motor tasks, which is an essential function for neurorehabilitation. In this study, we investigated the effects of cerebellar intermittent theta burst stimulation (c-iTBS), a high-frequency rTMS protocol able to increase cerebellar activity, on gait and balance in a sample of 20 hospitalized participants with MS, undergoing vestibular rehabilitation (VR), an exercise-based program primarily designed to reduce vertigo and dizziness, gaze instability, and/or imbalance and falls in MS. Patients were assigned to receive either c-iTBS or sham iTBS before being treated with VR during 2 weeks. VR consisted of two types of training: gaze stability and postural stability exercises. The primary outcome measure was the change from baseline in the Tinetti Balance and Gait scale (TBG). The secondary outcome measures were changes from baseline in Berg Balance Scale (BBS), Fatigue Severity Scale (FSS), Two Minute Walking Test (2MWT), and Timed 25-ft walk test (T25FW) scales. MS patients treated with c-iTBS-VR showed a significant improvement in the TBG as compared to patients treated with sham iTBS-VR. Moreover, MS patients in the c-iTBS groups showed better performances in the vestibular-ocular reflex exercises. Combined c-iTBS and VR improves gait and balance abilities more than standard VR treatment in MS patients with a high level of disability.

Assessing measurement invariance of MSQOL-54 across Italian and English versions.

PURPOSE: The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is a specific multiple sclerosis (MS) health-related quality of life inventory consisting of 52 items organized into 12 subscales plus two single items. No study was found in literature assessing its measurement invariance across language versions. We investigated whether MSQOL-54 items provide unbiased measurements of underlying constructs across Italian and English versions. METHODS: Three constrained levels of measurement invariance were evaluated: configural invariance where equivalent numbers of factors/factor patterns were required; metric invariance where equivalent factor loadings were required; and scalar invariance where equivalent item intercepts between groups were required. Comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) fit indices and their changes between nested models were used to assess tenability of invariance constraints. RESULTS: Overall, the dataset included 3669 MS patients: 1605 (44%) Italian, mean age 41 years, 62% women, 69% with mild level of disability; 2064 (56%) English-speaking (840 [41%] from North America, 797 [39%] from Australasia, 427 [20%] from UK and Ireland), mean age 46 years, 83% women, 54% with mild level of disability. The configural invariance model showed acceptable fit (RMSEA = 0.052, CFI = 0.904, SRMR = 0.046); imposing loadings and intercepts equality constraints produced negligible worsening of fit (ΔRMSEA < 0.001, ΔCFI = - 0.002, ΔSRMR = 0.002 for metric invariance; ΔRMSEA = 0.003, ΔCFI = - 0.013, ΔSRMR = 0.003 for scalar invariance). CONCLUSIONS: These findings support measurement invariance of the MSQOL-54 across the two language versions, suggesting that the questionnaire has the same meaning and the same measurement paramaters in the Italian and English versions.

eMSQOL-29: Prospective validation of the abbreviated, electronic version of MSQOL-54.

BACKGROUND: We recently devised a shortened version of the 54-item Multiple Sclerosis Quality of Life (MSQOL-54) in paper (MSQOL-29, consisting of 25 items forming 7 subscales and 4 single items, and one filter question for 3 'sexual function' items) and electronic format (eMSQOL-29). OBJECTIVES: To prospectively assess eMSQOL-29 psychometric properties, acceptability/equivalence versus MSQOL-29. METHODS: Multiple sclerosis (MS) patients ( n = 623; Expanded Disability Status Scale (EDSS) range 0.0-9.0) completed eMSQOL-29, Hospital Anxiety and Depression Scale, Functional Assessment of MS (FAMS), European Quality of life Five Dimensions-3L, and received EDSS and Symbol Digit Modalities Test (SDMT). Equivalence versus MSQOL-29 was assessed in 242 patients (randomized cross-over design). RESULTS: 'Sexual function' items were filtered out by 273 patients (47%). No multi-item scale had floor effect, while five had ceiling effect. Cronbach's alpha range was 0.88-0.90. Confirmatory factor analysis showed good overall fit and the two-factor solution for composite scores was confirmed. Criterion validity was sub-optimal for 'cognitive function' (vs SDMT, r = 0.25) and 'social function' (vs FAMS social function, r = 0.38). eMSQOL-29 equivalence was confirmed and its acceptability was good. CONCLUSION: eMSQOL-29 showed good internal consistency, factor structure and no floor effect, while most subscales had some ceiling effect. Criterion validity was sub-optimal for two subscales. Equivalence and acceptability were good.

Clinical staff work sampling in a neurorehabilitation hospital and its relationship to severity of disease.

AIM: Study aimed to analyse how rehabilitation staff spends working time on specific activities in a neurorehabilitation hospital and to determine the number of direct activities received by patients with different levels of disease severity. BACKGROUND: Few studies have investigated how clinical staff spends their time on activities in rehabilitation hospitals without considering at the same time all working categories and without reporting the number of direct activities received by patients with respect to their disease severity. DESIGN: Self-reported observational study. METHOD: Work Sampling Technique was used to record direct, indirect, unit-related and personal activities every 5 min for 2 days. RESULTS: Total of 6,974 activities were recorded over 581 working hours. Physiotherapists and nurses spent 75.2% and 54.8% of their time in direct activities and medical doctors only 25.4%. Total time of direct activities was significantly different among worker categories (p = 0.001) and depended on patients' disease severity (p = 0.020) in a different manner among worker categories (interaction: p = 0.010). This time ranged from almost 4 hr up to 6½ hr for the most severely affected patients. CONCLUSION: Type of work differed among professionals. Workload greatly depended on degree of patients' disability. IMPLICATIONS FOR NURSING MANAGEMENT: Nurses and therapists spent most of their time in direct activities with patients. Economic burden of neurorehabilitation may vary greatly depending on disease severity.

Randomized controlled trial of a home-based palliative approach for people with severe multiple sclerosis.

BACKGROUND: Evidence on the efficacy of palliative care in persons with severe multiple sclerosis (MS) is scarce. OBJECTIVE: To assess the efficacy of a home-based palliative approach (HPA) for adults with severe MS and their carers. METHODS: Adults with severe MS-carer dyads were assigned (2:1 ratio) to either HPA or usual care (UC). At each center, a multi-professional team delivered the 6-month intervention. A blind examiner assessed dyads at baseline, 3 months, and 6 months. Primary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients). RESULTS: Of 78 dyads randomized, 76 (50 HPA, 26 UC) were analyzed. Symptom burden (POS-S-MS) significantly reduced in HPA group compared to UC ( p = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months, and statistical significance was borderline in per-protocol analysis ( p = 0.062). Changes in SEIQoL-DW index did not differ in the two groups, as changes in secondary patient and carer outcomes. CONCLUSION: HPA slightly reduced symptoms burden. We found no evidence of HPA efficacy on patient quality of life and on secondary outcomes.

The Prevalence of Multiple Sclerosis in the Metropolitan Area of Rome: A Capture-Recapture Analysis.

BACKGROUND: Limited data are available on the prevalence of multiple sclerosis (MS) in central Italy. The objective of this study is to estimate MS prevalence in the metropolitan area of Rome. METHODS: We used the capture-recapture method to calculate prevalence estimates in the study area. The selected prevalence day was December 31, 2015. A total of 1,007 patients, with a definite diagnosis of MS according to the revised McDonald's criteria, were considered for crude, age- and sex-specific prevalence estimation. RESULTS: The overall crude prevalence rate was 146.2 cases per 100,000 (95% CI 119.9-172.5). A higher prevalence rate was recorded in females (194.1, 95% CI 149.6-238.6) than in males (93.0, 95% CI 67.2-118.8) with a female to male ratio of 1.8. Age-specific prevalence peaked in the 25-34 , 35-44 and 45-54 years class; moreover, it was found to increase up to the 45-54 years age group in females and the 35-44 years age group in males, decreasing thereafter. CONCLUSION: The results confirm that the metropolitan area of Rome is a high-risk area for MS.

Does robot-assisted gait training improve ambulation in highly disabled multiple sclerosis people? A pilot randomized control trial.

BACKGROUND: Robotic training is commonly used to assist walking training in patients affected by multiple sclerosis (MS) with non-conclusive results. OBJECTIVE: To compare the effect of robot-assisted gait training (RAGT) with that of conventional walking training (CWT) on gait competencies, global ability, fatigue and spasticity in a group of severely affected patients with MS. METHODS: A pilot, single-blind randomized controlled trial was conducted in 43 severe (Expanded Disability Status Scale (EDSS) score of 6-7.5) and non-autonomous ambulant in-patients with MS. Experimental group performed 12 sessions of RAGT, whereas control group performed the same amount of CWT. Primary outcome measures were gait ability assessed by 2 minutes walking test and Functional Ambulatory Category; secondary outcomes were global ability (modified Barthel Index), global mobility (Rivermead Mobility Index), severity of disease (EDSS) and subjectively perceived fatigue (Fatigue Severity Scale). RESULTS: The number of subjects who achieved a clinical significant improvement was significantly higher in RAGT than in CWT ( p < 0.05 for both primary outcome measures). RAGT also led to an improvement in all the other clinical parameters (global ability: p < 0.001, global mobility: p < 0.001, EDSS: p = 0.014 and fatigue: p = 0.001). CONCLUSIONS: RAGT improved the walking competencies in non-autonomous ambulant patients with MS, with benefits in terms of perceived fatigue.

Multiple sclerosis and amyotrophic lateral sclerosis: a human leukocyte antigen challenge.

Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are two different central nervous system pathology that, according to the most accredited hypotheses, recognize a different etiopathogenesis. The simultaneous occurrence of MS and ALS is quite unusual. To our knowledge, only three cases have been so far described by clinical, laboratory, and post-mortem studies. We report four new cases of this peculiar combination that have been observed and are herein described, included their human leukocyte antigen (HLA) profile studies. On the basis that three out of four patients in our case series presented HLA-B*18:01A, we may hypothesize that this antigen could play a role in developing both diseases.

Evaluation of the Impact of Cognitive Training on Quality of Life in Patients with Multiple Sclerosis.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of cognitive rehabilitation in a group of multiple sclerosis (MS) patients. METHODS: Thirty-four patients were included in this study and randomly allocated either to treatment with multidisciplinary rehabilitation plus cognitive training or to treatment with multidisciplinary rehabilitation alone. RESULTS: After 3 months of cognitive treatment, the patients assigned to the rehabilitation plus cognitive training group displayed an improvement in the cognitive test of executive function and a marked improvement in quality of life (QoL). The patients treated with multidisciplinary rehabilitation without cognitive training improved in the physical composite score alone. Both groups of patients displayed an improvement in depression, though the improvement was confirmed at the 6-month follow-up examination (p = 0.036) only in patients treated with multidisciplinary rehabilitation plus cognitive training. CONCLUSIONS: Our results indicate that the multidisciplinary rehabilitation treatment is the best approach to treat MS. The specific effect of each treatment needs to be assessed to be able to determine its role within a multidisciplinary approach. Cognitive rehabilitation is an important aspect of this multidisciplinary approach insofar as it may improve the QoL of MS people.

T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis.

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by persistent inflammation orchestrated by cluster of differentiation (CD) 4 T helper (Th) cells. In particular, Th1 and Th17 cells amplify, whereas T regulatory (Treg) cells moderate inflammation. The role of other Th subsets in MS is not clear. In the present study, we investigated the generation of different Th responses by human dendritic cells (DCs) in MS. We compared the production of several Th cytokines by naive CD4+ T-cells polarized with myeloid and plasmacytoid DCs (mDCs and pDCs) in healthy donors (HD) and relapsing-remitting (RR)-MS patients. We found that resiquimod-stimulated mDCs were able to activate Th17 differentiation, whereas pDCs induced interleukin (IL)-10-producing Th cells. Surprisingly, resiquimod-stimulated pDCs from MS patients also significantly induced the differentiation of Th9 cells, which produce IL-9 and are known to be involved in allergic diseases. We investigated the potential role of IL-9 in MS. We found that IL-9 activated signal transducer and activator of transcription (STAT) 1 and STAT5 phosphorylation and interfered with IL-17 and interferon (IFN) regulatory transcription factor (IRF)-4 expression in Th17-polarized cells. Moreover, in the cerebrospinal fluid (CSF) of 107 RR-MS patients, IL-9 inversely correlated with indexes of inflammatory activity, neurodegeneration and disability progression of MS. High levels of IL-9 were associated with the absence of IL-17 in the CSF of RR-MS patients. Our results demonstrate a Th9-inducing potential of pDCs in MS, suggesting an immunoregulatory role leading to attenuation of the exaggerated Th17 inflammatory response.

Chronic Pain in Multiple Sclerosis Patients: Utility of Sensory Quantitative Testing in Patients with Fibromyalgia Comorbidity.

BACKGROUND: Lower thermal and discomfort thresholds may predispose multiple sclerosis (MS) patients to chronic pain, but a possible effect of fibromyalgia (FM) comorbidity has never been investigated. Aims were to investigate the thermal and discomfort thresholds in the evaluation of pain intensity between MS patients with FM (PFM+) and MS patients with pain not associated to FM (PFM-). METHODS: One hundred thirty three MS patients were investigated for chronic pain. FM was assessed according to the 1990 ACR diagnostic criteria. An algometer was used to measure the thresholds in the patients and 60 matched healthy subjects. RESULTS: Chronic pain was present in 88 (66.2%) patients; 12 (13.6%) had neuropathic pain, 22 (17.3%) were PFM+ and 65 (48.9%) PFM-. PFM+ were predominantly female (p = 0.03) and had a greater EDSS (p = 0.01) than NoP; no other significant differences emerged than PFM-. The thresholds were lower in MS patients than controls (p < 0.01), mainly in the PFM+. FM severity influenced the thermal threshold (p < 0.001), while the female gender influenced the discomfort threshold (p < 0.001). CONCLUSION: Thermal and discomfort thresholds were lower in patients than controls and were the lowest in PFM+. Their more severely impaired thermal threshold supports a neurophysiological basis of such association.

Chronic pain in multiple sclerosis: is there also fibromyalgia? An observational study.

BACKGROUND: Chronic pain is common in persons with multiple sclerosis (MS), but the co-morbidity of fibromyalgia (FM) has yet to be investigated in MS. Objectives of the study were to evaluate, among the various types of chronic pain, the frequency of FM in MS and its impact on MS patients' health-related quality of life (HRQoL). MATERIAL AND METHODS: 133 MS patients were investigated for the presence and characterization of chronic pain within 1 month of assessment. A rheumatologist assessed the presence FM according to the 1990 ACR diagnostic criteria. Depression, fatigue, and HRQoL were also assessed by means of specific scales. RESULTS: Chronic pain was present in 66.2% of patients (musculoskeletal in 86.3%; neuropathic in 13.7%; absent in 33.8% [called NoP]). Pain was diagnosed with FM (PFM+) in 17.3% of our MS patients, while 48.9% of them had chronic pain not FM type (PFM-); the prevalence of neuropathic pain in these 2 sub-groups was the same. PFM+ patients were prevalently females and had a higher EDSS than NoP. The PFM+ patients had a more pronounced depression than in the NoP group, and scored the worst in both physical and mental QoL. CONCLUSIONS: In our sample of MS patients we found a high prevalence of chronic pain, with those patients displaying a higher disability and a more severe depression. Moreover, FM frequency, significantly higher than that observed in the general population, was detected among the MS patients with chronic pain. FM occurrence was associated with a stronger impact on patients' QoL.

From high- to low-frequency administered interferon-beta for multiple sclerosis: a multicenter study.

OBJECTIVES: To investigate whether clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) who required a reduction of administration frequency of interferon-beta (IFNB) were similar to those of patients who did not. METHODS: We identified three subgroups of patients under treatment for 24 months with subcutaneous (sc) high-frequency IFNB-1a or -1b: those continuing to receive IFNB according to the drug label (recommended frequency group), those reducing the administration frequency of sc IFNB-1a or -1b (reduced frequency group), and those switched to once weekly intramuscular (im) IFNB (switched group). All patients were followed for further 24 months. The occurrence of relapse, MRI activity and disability worsening were considered as outcome measures. RESULTS: We identified 308 patients, 201 in the recommended frequency group, 70 in the reduced frequency group, and 37 in the switched group. Patients in the reduced frequency group had increased risk for relapses (HR = 1.95, p < 0.001) and MRI activity (HR = 1.41, p < 0.001), while patients in the switched group had increased risk for relapses (HR = 1.67, p = 0.012), but not for MRI activity (HR = 1.26, p = 0.08) than those in the recommended frequency group. Predictors for disease activity re-start after the reduction of IFNB administration frequency were younger age, higher pre-IFNB relapse rate, and reducing sc IFNB frequency to twice weekly rather than switching to im IFNB-1a once weekly. CONCLUSION: Our findings discourage the reduction of sc IFNB administration frequency, especially in younger patients with a higher pre-IFNB relapse rate. However, switching to im IFNB-1a may be considered in some selected cases.

Altered cerebral vasoregulation predicts the outcome of patients with partial anterior circulation stroke.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the correlation between cerebral hemodynamic changes and the evolution of neurological deficit after stroke. METHODS: We included 65 patients with non-lacunar stroke admitted to a rehabilitation hospital within 4 weeks from the event. An evaluation of cerebrovascular reactivity to hypercapnia was performed with transcranial Doppler ultrasonography using the breath-holding index (BHI). Activities of daily living status was measured by the Barthel Index (BI) and impairment of mobility was assessed by means of the Rivermead Mobility Index (RMI). Multivariate analyses were performed using effectiveness of treatment, evaluated on BI and RMI as dependent variables. Independent variables were BHI values, age, sex, length of stay, hypertension, smoking habit, presence of aphasia and neglect, poststroke depression, and the degree of severity of stroke. RESULTS: The effectiveness on BI was associated positively with normal BHI values and with neurological severity at admission, measured by the Canadian Neurological Scale. The regression coefficients for effectiveness on RMI showed that the most relevant predictor was ipsilateral BHI (the slope resulted equal to 5.8), followed by age (a 10-year age difference is expected to diminish the effectiveness by about 4.3%) and by depression (depressed patients have almost 11% less effectiveness than non-depressed patients). CONCLUSION: These findings suggest that a satisfactory recovery from neurologic deficits requires a preserved cerebrovascular reactivity in the lesioned hemisphere despite the presence of an anatomic lesion.

Usability of a Hybrid System Combining P300-Based Brain-Computer Interface and Commercial Assistive Technologies to Enhance Communication in People With Multiple Sclerosis.

Brain-computer interface (BCI) can provide people with motor disabilities with an alternative channel to access assistive technology (AT) software for communication and environmental interaction. Multiple sclerosis (MS) is a chronic disease of the central nervous system that mostly starts in young adulthood and often leads to a long-term disability, possibly exacerbated by the presence of fatigue. Patients with MS have been rarely considered as potential BCI end-users. In this pilot study, we evaluated the usability of a hybrid BCI (h-BCI) system that enables both a P300-based BCI and conventional input devices (i.e., muscular dependent) to access mainstream applications through the widely used AT software for communication "Grid 3." The evaluation was performed according to the principles of the user-centered design (UCD) with the aim of providing patients with MS with an alternative control channel (i.e., BCI), potentially less sensitive to fatigue. A total of 13 patients with MS were enrolled. In session I, participants were presented with a widely validated P300-based BCI (P3-speller); in session II, they had to operate Grid 3 to access three mainstream applications with (1) an AT conventional input device and (2) the h-BCI. Eight patients completed the protocol. Five out of eight patients with MS were successfully able to access the Grid 3 via the BCI, with a mean online accuracy of 83.3% (± 14.6). Effectiveness (online accuracy), satisfaction, and workload were comparable between the conventional AT inputs and the BCI channel in controlling the Grid 3. As expected, the efficiency (time for correct selection) resulted to be significantly lower for the BCI with respect to the AT conventional channels (Z = 0.2, p < 0.05). Although cautious due to the limited sample size, these preliminary findings indicated that the BCI control channel did not have a detrimental effect with respect to conventional AT channels on the ability to operate an AT software (Grid 3). Therefore, we inferred that the usability of the two access modalities was comparable. The integration of BCI with commercial AT input devices to access a widely used AT software represents an important step toward the introduction of BCIs into the AT centers' daily practice.