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2.
Ann Vasc Surg ; 62: 275-286, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31445091

RESUMO

BACKGROUND: Venous percutaneous transluminal angioplasty (vPTA) in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) have shown contradictory results. The aim of the study is to evaluate the efficacy of the procedure in a randomized wait list control study. METHODS: 66 adults with neurologist-confirmed diagnosis of MS and sonographic diagnosis of CCSVI were allocated into vPTA-yes group (n = 31) or vPTA-not group (n = 35, control group). vPTA was performed immediately 15 days after randomization in the PTA-yes group and 6 months later in the control group. Evoked potentials (EPs), clinical-functional measures (CFMs), and upper limb kinematic measures (ULKMs) were measured at baseline (T0) and six months after in both groups, just before the venous angioplasty in the vPTA-not group (T1). RESULTS: Comparing the vPTA-yes and vPTA-not group, the CFM-derived composite functional outcome showed 11 (37%) versus 7 (20%) improved, 1 (3%) versus 3 (8%) stable, 0 versus 7 (20%) worsened, and 19 (61%) versus 18 (51%) mixed patients (χ2 = 8.71, df = 3, P = 0.03). Unadjusted and adjusted (for baseline confounding variables) odds ratio at 95% confidence interval were, respectively, 1.93 (1.3-2.8), P value 0.0007, and 1.85 (1.2-1.7), P value 0.002. EP- and ULKM-derived composite functional outcome showed no significant difference between the two groups. CONCLUSIONS: Venous angioplasty can positively impact a few CFMs especially for the quality of life but achieving disability improvement is unlikely.


Assuntos
Angioplastia , Veias Cerebrais , Transtornos Cerebrovasculares/terapia , Esclerose Múltipla Crônica Progressiva/terapia , Esclerose Múltipla Recidivante-Remitente/terapia , Extremidade Superior/inervação , Insuficiência Venosa/terapia , Adolescente , Adulto , Idoso , Angioplastia/efeitos adversos , Fenômenos Biomecânicos , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/fisiopatologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Doença Crônica , Potencial Evocado Motor , Humanos , Itália , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/diagnóstico , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/fisiopatologia , Adulto Jovem
3.
BMC Neurol ; 19(1): 314, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810462

RESUMO

BACKGROUND: The relevance of regular moderate to intense exercise for ameliorating psychomotor symptoms in persons with multiple sclerosis (pwMS) is becoming increasingly evident. Over the last two decades, emerging evidence from clinical studies and animal models indicate immune regulatory mechanisms in both periphery and the central nervous system that may underlie these beneficial effects. The integrity of the blood-brain barrier as the main structural interface between periphery and brain seems to play an important role in MS. Reducing the secretion of proteolytic matrix metalloproteinases (MMP), i.e. MMP-2, as disruptors of blood-brain barrier integrity could have profound implications for MS. METHODS: In this two-armed randomized controlled trial 64 participants with relapsing-remitting MS (RRMS) (EDSS 0-4.0) will be allocated to either an intervention group or a passive wait list control group. The intervention group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks in a community-based and publicly available setting. Changes in serum concentration of MMP-2 will be the primary outcome. Secondary outcomes are numbers of immune cell subsets, soluble (anti-) inflammatory factors, physical capacity, cognitive performance, physical activity behavior, gait performance, and patient-reported outcomes. All outcome measures will be assessed at baseline and after week 12 with an additional blood sampling before, during and immediately after a single training session in week 6. DISCUSSION: To our knowledge, this will be the first RCT to investigate both the acute and chronic effects of a community-based intense functional resistance and endurance exercise regimen in persons with RRMS. Combining analysis of biological and cognitive or psychological outcomes may provide a better understanding of the MS-specific symptomology. TRIAL REGISTRATION: DRKS00017091; 05th of April, 2019; International Clinical Trials Registry Platform.


Assuntos
Terapia por Exercício , Metaloproteinase 2 da Matriz/sangue , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Encéfalo/fisiopatologia , Exercício Físico/fisiologia , Humanos , Atividade Motora/fisiologia , Método Simples-Cego
4.
BMC Bioinformatics ; 20(Suppl 6): 623, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822261

RESUMO

BACKGROUND: Multiple Sclerosis (MS) is an immune-mediated inflammatory disease of the Central Nervous System (CNS) which damages the myelin sheath enveloping nerve cells thus causing severe physical disability in patients. Relapsing Remitting Multiple Sclerosis (RRMS) is one of the most common form of MS in adults and is characterized by a series of neurologic symptoms, followed by periods of remission. Recently, many treatments were proposed and studied to contrast the RRMS progression. Among these drugs, daclizumab (commercial name Zinbryta), an antibody tailored against the Interleukin-2 receptor of T cells, exhibited promising results, but its efficacy was accompanied by an increased frequency of serious adverse events. Manifested side effects consisted of infections, encephalitis, and liver damages. Therefore daclizumab has been withdrawn from the market worldwide. Another interesting case of RRMS regards its progression in pregnant women where a smaller incidence of relapses until the delivery has been observed. RESULTS: In this paper we propose a new methodology for studying RRMS, which we implemented in GreatSPN, a state-of-the-art open-source suite for modelling and analyzing complex systems through the Petri Net (PN) formalism. This methodology exploits: (a) an extended Colored PN formalism to provide a compact graphical description of the system and to automatically derive a set of ODEs encoding the system dynamics and (b) the Latin Hypercube Sampling with PRCC index to calibrate ODE parameters for reproducing the real behaviours in healthy and MS subjects.To show the effectiveness of such methodology a model of RRMS has been constructed and studied. Two different scenarios of RRMS were thus considered. In the former scenario the effect of the daclizumab administration is investigated, while in the latter one RRMS was studied in pregnant women. CONCLUSIONS: We propose a new computational methodology to study RRMS disease. Moreover, we show that model generated and calibrated according to this methodology is able to reproduce the expected behaviours.


Assuntos
Simulação por Computador , Esclerose Múltipla Recidivante-Remitente , Biologia Computacional , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Gravidez , Recidiva
5.
PLoS One ; 14(12): e0226775, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31869375

RESUMO

The cognitive-motor interference (CMI) produced by simultaneous performance of a cognitive and a motor task has been proposed as a marker of real-life impairment of people with Multiple Sclerosis (pwMS), yet there is no consensus on the dual task (DT) procedure. This study aimed to compare DT performance of pwMS and healthy controls (HC) under different instructions and to examine its association with neuropsychological and clinical variables. PwMS (N = 23; relapsing-remitting course) and HC (N = 24) completed the cognitive (Verbal Fluency) and motor (walking) tasks under three conditions: independently or as single task (ST), both tasks simultaneously at best capacity or double prioritization (DT-DP), and only the cognitive task at best capacity while walking at preferred speed or cognitive prioritization (DT-CP). Compared to HC, pwMS walked significantly slower and produced less correct words under all conditions. The distance walked by pwMS and HC significantly differed between conditions (DT-CP< DT-DP< ST). PwMS produced more words during ST respective to DT-DP and DT-CP, with no difference between both DT conditions. HC showed no differences in cognitive performance between conditions. Motor and cognitive dual-task costs (DTC) were similar between groups. Only in pwMS, the cognitive DTC of DT-DP was different from zero. CMI measures correlated with neuropsychological, symptomatic, physiological (cognitive event-related potentials) and clinical variables. These results suggest that cognitive performance while walking is impaired in pwMS, but not in HC. CMI over cognitive performance might be a potential early marker of cognitive decline in pwMS, which may be enhanced by the instruction to prioritize both tasks in DT.


Assuntos
Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Adulto , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/psicologia , Desempenho Psicomotor , Análise e Desempenho de Tarefas
6.
Neurology ; 93(20): e1906-e1916, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31594857

RESUMO

OBJECTIVE: In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D3 in patients with RRMS. METHODS: Eligible patients with RRMS treated with SC interferon-ß-1a (IFN-ß-1a) 44 µg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-ß-1a plus placebo (n = 116) or SC IFN-ß-1a plus oral high-dose vitamin D3 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48. RESULTS: At 48 weeks, 36.3% of patients who received high-dose vitamin D3 had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; p = 0.80). Compared with placebo, the high-dose vitamin D3 group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; p = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: -0.074; p = 0.035). CONCLUSIONS: SOLAR did not establish a benefit for high-dose vitamin D3 as add-on to IFN-ß-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01285401. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS treated with SC IFN-ß-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Colecalciferol/administração & dosagem , Interferon beta-1a/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Encéfalo/diagnóstico por imagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
7.
Res Theory Nurs Pract ; 33(3): 229-245, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31615943

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to gain insights and understanding into the lived experience of relapsing remitting multiple sclerosis (RRMS) in order to better inform patient-centerd nursing and healthcare. METHODS: This qualitative study used life history methodology, a form of focused ethnography, to explore the life history of 13 study participants living with RRMS. Semi-structured interviews were transcribed and analysed using thematic analysis. FINDINGS: A total of eight key themes emerged, explaining the journey of living with RRMS. Commencing with "Piecing Together the Puzzle" of symptoms at the beginning of the RRMS journey, followed by "(Re)defining ME now that I have RRMS," "Battling the Demons," the experiences of "Surplus Suffering," negotiating "High Invisibility," gaining control by "Taming the Beast," learning "The DMT Dance," and ultimately "Holding Hands with Hope," expressing hope and practising purposeful positivity. IMPLICATIONS FOR PRACTICE: The eight key themes of living with RRMS were reflective of the ebbs and flows of life. By gaining these insights into the world of people living with RRMS, it is anticipated that clinical nursing care and quality of life for people living with this chronic neurological disease may be improved.


Assuntos
Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/enfermagem , Assistência Centrada no Paciente , Pesquisa Qualitativa , Qualidade de Vida
8.
Neurology ; 93(20): e1852-e1866, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31611336

RESUMO

OBJECTIVE: To characterize the distribution and regional evolution of cervical cord atrophy in patients with multiple sclerosis (MS) in a multicenter dataset. METHODS: MRI and clinical evaluations were acquired from 179 controls and 435 patients (35 clinically isolated syndromes [CIS], 259 relapsing-remitting multiple sclerosis [RRMS], 99 secondary progressive multiple sclerosis [SPMS], and 42 primary progressive multiple sclerosis [PPMS]). Sixty-nine controls and 178 patients underwent a 1-year MRI and clinical follow-up. Patients were classified as clinically stable/worsened according to their disability change. Longitudinal changes of cord atrophy were investigated with linear mixed-effect models. Sample size calculations were performed using age-, sex- and site-adjusted annualized percentage normalized cord cross-sectional area (CSAn) changes. RESULTS: Baseline CSAn was lower in patients with MS vs controls (p < 0.001), but not different between controls and patients with CIS or between patients with early RRMS (disease duration ≤5 years) and patients with CIS. Patients with late RRMS (disease duration >5 years) showed significant cord atrophy vs patients with early RRMS (p = 0.02). Patients with progressive MS had decreased CSAn (p < 0.001) vs patients with RRMS. Atrophy was located between C1/C2 and C5 in patients with RRMS vs patients with CIS, and widespread along the cord in patients with progressive MS vs patients with RRMS, with an additional C5/C6 involvement in patients with SPMS vs patients with PPMS. At follow-up, CSAn decreased in all phenotypes (p < 0.001), except CIS. Cord atrophy rates were highest in patients with early RRMS and clinically worsened patients, who had a more widespread cord involvement than stable patients. The sample size per arm required to detect a 50% treatment effect was 118 for patients with early RRMS. CONCLUSIONS: Cord atrophy increased in MS during 1 year, except for CIS. Faster atrophy contributed to explain clinical worsening.


Assuntos
Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Adolescente , Adulto , Idoso , Atrofia , Vértebras Cervicais , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Medula Espinal/patologia , Adulto Jovem
9.
Postgrad Med ; 131(7): 523-532, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478421

RESUMO

Objectives: Many people affected by multiple sclerosis (MS) experience cognitive impairment, especially decreases in information processing speed (PS). Neural disconnection is thought to represent the neural marker of this symptom, although the role played by alterations of specific functional brain networks still remains unclear. The aim is to investigate and compare patterns of association between PS-demanding cognitive performance and functional connectivity across two MS phenotypes. Methods: Forty patients with relapsing-remitting MS (RRMS) and 25 with secondary progressive MS (SPMS) had neuropsychological and MRI assessments. Multiple regression models were used to investigate the relationship between performance on tests of visuomotor and verbal PS, and on the verbal fluency tests, and functional connectivity of four cognitive networks, i.e. left and right frontoparietal, salience and default-mode, and two control networks, i.e. visual and sensorimotor. Results: Patients with SPMS were older and had longer disease history than patients with RRMS and presented with worse overall clinical conditions: higher disease severity, total lesion volume, and cognitive impairment rates. However, in both patient samples, cognitive performance across tests was negatively correlated with functional connectivity of the salience and default-mode networks, and positively with connectivity of the left frontoparietal network. Only the visuomotor PS scores of the RRMS group were also associated with connectivity of the sensorimotor network. Conclusions: PS-demanding cognitive performance in patients with MS appears mainly associated with strength of functional connectivity of frontal networks involved in the evaluation and manipulation of information, as well as the default mode network. These results are in line with the hypothesis that multiple neural networks are needed to support normal cognitive performance across MS phenotypes. However, different PS measures showed partially different patterns of association with functional connectivity. Therefore, further investigations are needed to clarify the contribution of inter-network communication to specific cognitive deficits due to MS.


Assuntos
Encéfalo/diagnóstico por imagem , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Adulto , Idoso , Encéfalo/fisiopatologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/psicologia , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Crônica Progressiva/psicologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Desempenho Psicomotor
10.
J Neurol ; 266(12): 3098-3107, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31535270

RESUMO

BACKGROUND: The increase in disease-modifying drugs (DMDs) allows individualization of treatment in relapsing multiple sclerosis (RMS); however, the long-term impact of different treatment sequences is not well established. This is particularly relevant for MS patients who may need to postpone more aggressive DMD strategies. OBJECTIVE: To evaluate different therapeutic strategies and their long-term outcomes, measured as relapses and confirmed disability progression (CDP), in MS 'real-world' settings. METHODS: Multicentre, observational, retrospectively acquired cohort study evaluating the long-term impact of different treatment strategies on disability outcomes in patients with RMS in the Italian MS Register. RESULTS: We evaluated 1152 RMS-naïve patients after propensity-score adjustment. Patients included were receiving: interferon beta-1a (IFN-ß1a) 44 µg switching to fingolimod (FTY; IFN-switchers; n = 97); FTY only (FTY-stayers; n = 157); IFN-ß1a only (IFN-stayers; n = 849). CDP and relapses did not differ between FTY-stayers and IFN-switchers [HR (95% CI) 0.99 (0.48-2.04), p = 0.98 and 0.81 (0.42-1.58), p = 0.55, respectively]. However, IFN-stayers showed increased risk of relapses compared with FTY-stayers [HR (95% CI) 1.46 (1.00-2.12), p = 0.05]. CONCLUSION: The ideal treatment option for MS is becoming increasingly complex, with the need to balance benefit and risks. Our results suggest that starting with FTY affects the long-term disease outcome similarly to escalating from IFN-ß1a to FTY.


Assuntos
Progressão da Doença , Cloridrato de Fingolimode/farmacologia , Fatores Imunológicos/farmacologia , Interferon beta-1a/farmacologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros , Índice de Gravidade de Doença , Adulto , Esquema de Medicação , Feminino , Cloridrato de Fingolimode/administração & dosagem , Humanos , Fatores Imunológicos/administração & dosagem , Interferon beta-1a/administração & dosagem , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
PLoS One ; 14(9): e0222288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31513613

RESUMO

OBJECTIVE: Systematic Review was used to evaluate the efficacy and safety of Dalfampridine (DAP) in the treatment of Mobility Disability (MS) in patients with Multiple Sclerosis. METHODS: Clinical randomized controlled studies about DAP and placebo in the treatment of Mobility Disability in patients with Multiple Sclerosis until March 2019 were explored by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Literature screening, data extraction, quality assessment, and statistical analysis were performed by using Stata 14.0. RESULTS: 10 papers were included in the meta-analysis, and the number of patients was 2100. In conclusion, the application of DAP in clinical can significantly improve the Mobility Disability of patients [OR = 2.73, 95%CI (1.66, 4.50), P<0.001, I2 = 74.1%] and boost the mobility speed of patients in Timing 24 Minute Walk Test (T24FW) [SMD = 3,08, 95%CI(1,58, 4.58), P<0.001, I2 = 98.7%]. There are no significant differences of the incidence of adverse events [RR = 1.06, 95%CI (0.99, 1.14), P = 0.928, I2 = 0.0%] and urinary tract infection [RR = 1.21, 95%CI(0.91, 1.60), P = 0.145, I2 = 37.2%] between the DAP test group (Doses≤10 mg) and the placebo control group, and the incidence of adverse events [RR = 1.14, 95%CI(1.02, 1.28), P = 0.793, I2 = 0.0%] and urinary tract infection[RR = 3.05, 95%CI(1.04, 8.99), P = 0.680, I2 = 0.0%] for the DAP test group (Doses>10 mg) is a litter higher than the placebo control group. CONCLUSION: DAP can effectively improve Mobility Disability in patients with Multiple Sclerosis, which is safe and reliable in specific DAP usage doses.


Assuntos
4-Aminopiridina/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , 4-Aminopiridina/farmacologia , Pessoas com Deficiência , Humanos , Imunossupressores/uso terapêutico , Limitação da Mobilidade , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Amplitude de Movimento Articular
12.
BMC Neurol ; 19(1): 231, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558148

RESUMO

BACKGROUND: Clinical and imaging follow-up coupled with cerebrospinal fluid (CSF) and possibly serum profiling could provide information on disease activity and disability evolution in multiple sclerosis patients. CASE PRESENTATION: We describe the case of a relapsing-remitting MS patient whose history was characterized by failure of several therapeutic approaches and sustained disease activity. By using a highly sensitive immunoassay methodology, we examined protein expression of 70 inflammatory/cytotoxic molecules in two consecutive paired CSF and serum samples, obtained respectively in 2006 and 2013. At disease diagnosis, elevated CSF protein levels of an inflammatory pattern, including CXCL13, CXCL12, IFNγ, TNF, sTNFR1, IL8, sCD163, APRIL, BAFF, pentraxin III and MMP2 were found compared with a group of controls. At the second lumbar puncture, sustained disease activity was accompanied by considerable (more than 2 fold changes) increase expression of most of these inflammatory molecules while no significant changes in serum inflammatory markers were detected in the two consecutive serum samples. CONCLUSIONS: Elevated CSF protein expression of pro-inflammatory mediators, possibly specifically associated to GM demyelination, could remain stable or increase over time in patients with active multiple sclerosis. We underline the role of fluid analysis in understanding the pathophysiology of the disease and providing information on possible markers of disease activity and evolution.


Assuntos
Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Adulto , Feminino , Humanos , Esclerose Múltipla Recidivante-Remitente/sangue
13.
J Neurol ; 266(12): 3031-3037, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494713

RESUMO

BACKGROUND: Spinal cord (SC) involvement correlates with poor prognosis in patients with multiple sclerosis (MS). Nevertheless, there is no consensus on the use of SC-MRI at follow-up, mainly because of the belief that SC lesions are nearly always symptomatic. OBJECTIVES: The aim of the present study was to investigate the frequency of asymptomatic SC combined unique activity (CUA, new/enlarging T2 or gadolinium-positive [Gd+] lesions) on MRI in a cohort of patients diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS). METHODS: We retrospectively investigated all scans showing SC-CUA in patients with CIS or RRMS referred to a single Italian MS centre. We determined whether they were symptomatic and whether they had associated brain radiological activity. RESULTS: In 340 SC-MRI scans with SC-CUA (230 patients), SC-CUA was asymptomatic in 31.2%; 12.1% of SC-CUA had neither clinical activity nor brain radiological activity (44.5% and 25.4%, respectively, considering only follow-up SC-CUA). At multivariate analysis asymptomatic SC-CUAs were associated with older age at onset (34.0 ± 10.37 vs 31.0 ± 9.99 years, p = 0.006), non-spinal onset (76.4 vs 47.4%, p < 0.001), lower EDSS score at MRI (1.8 ± 0.93 vs 2.4 ± 1.28, p = 0.001) and lower number of Gd+ SC lesions (0.1 ± 0.33 vs 0.3 ± 0.54, p = 0.04), compared to symptomatic SC-CUAs. CONCLUSIONS: A substantial proportion of our patients had SC-CUA without clinical symptoms and/or without concomitant brain MRI activity. In these patients, SC-CUA was the only sign of disease activity, suggesting that regular SC-MRI follow-up is required for reliable assessment of radiological activity and may improve the management of patients with MS.


Assuntos
Encéfalo/patologia , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Medula Espinal/patologia , Adulto , Encéfalo/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagem
14.
J Neurol ; 266(12): 3022-3030, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31493037

RESUMO

Prolonged walking is typically impaired among people with multiple sclerosis (pwMS), however, it is unclear what the contributing factors are or how to evaluate this deterioration. We aimed to determine which gait features become worse during sustained walking and to examine the clinical correlates of gait fatigability in pwMS. Fifty-eight pwMS performed the 6-min walk test while wearing body-fixed sensors. Multiple gait domains (e.g., pace, rhythm, variability, asymmetry and complexity) were compared across each minute of the test and between mild- and moderate-disability patient groups. Associations between the decline in gait performance (i.e., gait fatigability) and patient-reported gait disability, fatigue and falls were also determined. Cadence, stride time variability, stride regularity, step regularity and gait complexity significantly deteriorated during the test. In contrast, somewhat surprisingly, gait speed and swing time asymmetry did not change. As expected, subjects with moderate disability (n = 24) walked more poorly in most gait domains compared to the mild-disability group (n = 34). Interestingly, a group × fatigue interaction effect was observed for cadence and gait complexity; these measures decreased over time in the moderate-disability group, but not in the mild group. Gait fatigability rate was significantly correlated with physical fatigue, gait disability, and fall history. These findings suggest that sustained walking affects specific aspects of gait, which can be used as markers for fatigability in MS. This effect on gait depends on the degree of disability, and may increase fall risk in pwMS. To more fully understand and monitor correlates that reflect everyday walking in pwMS, multiple domains of gait should be quantified.


Assuntos
Fadiga/fisiopatologia , Transtornos Neurológicos da Marcha/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Adulto , Fadiga/etiologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/complicações , Índice de Gravidade de Doença , Teste de Caminhada
15.
Neurology ; 93(19): e1778-e1786, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484710

RESUMO

OBJECTIVE: To assess the onset of ocrelizumab efficacy on brain MRI measures of disease activity in the phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled phase III studies in relapsing multiple sclerosis (RMS). METHODS: Brain MRI activity was determined in the phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) ß-1a (30 µg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the phase III OPERA (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN-ß-1a (44 µg). RESULTS: In patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by week 4 vs placebo (p = 0.042) and by week 8 vs intramuscular IFN-ß-1a (p < 0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between weeks 4 and 8 vs both placebo and IFN-ß-1a (both p < 0.001). In patients with RMS, ocrelizumab significantly reduced ARR (p = 0.005) and the probability of time to first protocol-defined relapse (p = 0.014) vs subcutaneous IFN-ß-1a within the first 8 weeks. CONCLUSION: Epoch analysis of MRI-measured lesion activity in the phase II study and relapse rate in the phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS and RMS, ocrelizumab suppressed MRI activity within 4 weeks and clinical disease activity within 8 weeks.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Encéfalo/diagnóstico por imagem , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Adulto , Feminino , Humanos , Interferon beta-1a/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Recidiva , Fatores de Tempo , Resultado do Tratamento
16.
Expert Opin Drug Saf ; 18(10): 925-948, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429602

RESUMO

Introduction: In the last 20 years the armamentarium for multiple sclerosis (MS) treatment has been enriched from an increasingly wider variety of new drugs in order to reach a better control of the disease with a better patient compliance. Areas covered: With this great variety of therapeutic options, physicians may face new and major challenges. The huge amount of data from pilot studies and real-life settings showed that the first-line therapies have a better safety profile. On the other hand, the risks associated with newer drugs, with more selective mechanism of action and targeting specific pathways of MS pathophysiology, are not yet fully established. In particular, real-life use of these advanced drugs has raised important safety issues as long-term effects and potential risks are not yet known and remain to be carefully evaluated. Expert opinion: No time like the present, the physician faces new and major challenges in order to choose the best available therapy for MS. With the increasing number of drugs for treating MS and the lack of safety data, observational studies and post-marketing surveillance activities are crucial in order to improve the knowledge about the safety profile of these drugs and the therapeutic management in clinical practice settings.


Assuntos
Fatores Imunológicos/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Vigilância de Produtos Comercializados , Animais , Desenho de Fármacos , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Adesão à Medicação , Esclerose Múltipla Recidivante-Remitente/fisiopatologia
17.
Postgrad Med ; 131(7): 453-460, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31469966

RESUMO

Objectives: Recent evidence suggests an association between functional capacity and cognitive function, at least in older adults. The aim of this cross-sectional study was to examine the association between cognitive function, functional capacity, isokinetic leg strength, health-related quality of life (HRQOL), sleep quality, body fat, handgrip strength, and fatigue among a sample of MS patients. Methods: Fifty-one relapsing-remitting MS patients (age: 38.4 ± 7.1 yrs; 30 females) were recruited and agreed to participate in this study. Cognitive function was assessed by the Paced Auditory Serial Addition Test (PASAT). Functional capacity was examined using various functional tests commonly used in MS patients. Maximal voluntary unilateral leg strength was assessed using isokinetic dynamometer. Isometric handgrip strength was assessed by a dynamometer. Total body and visceral fat levels were assessed via bioelectrical impedance analyzers. Finally, the patients' HRQOL, sleep quality, and fatigue levels were evaluated using specific questionnaires. Results: A significant association was found between the PASAT score and the performance score in various functional capacity tests (p < 0.050). On the other hand, a weak but statistically significant association was found between the PASAT score and isokinetic strength of knee extensors (r = 0.319, p = 0.022) and knee flexors (r = 0.354 p = 0.011). Poor sleep quality was associated with lower performance in all the functional capacity tests examined (p < 0.05) whilst was negatively associated with the PASAT score (r = -0.334, p = 0.017). The multivariate regression analysis revealed that the performance on the TUG test was a significant predictor of cognitive function. Conclusion: Based on the results of this study, functional capacity was found to be associated with both impaired cognitive performance and low HRQOL in MS patients. In addition, an association between sleep quality and cognitive performance was revealed, confirming existing literature. Functional capacity as assessed by the TUG test emerged as the best predictor of cognitive function.


Assuntos
Cognição , Fadiga/fisiopatologia , Força da Mão/fisiologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Qualidade de Vida , Tecido Adiposo , Adulto , Composição Corporal , Estudos Transversais , Impedância Elétrica , Fadiga/psicologia , Feminino , Músculos Isquiossurais , Humanos , Gordura Intra-Abdominal , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/psicologia , Força Muscular/fisiologia , Testes Neuropsicológicos , Músculo Quadríceps , Sono , Inquéritos e Questionários , Teste de Caminhada
18.
PLoS One ; 14(7): e0219594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31306457

RESUMO

Functional neuroanatomy of cognitive impairment in multiple sclerosis is currently still a challenge. During the progression of the disease, several cognitive mechanisms deteriorate thus diminishing the patient's quality of life. A primary objective in the cognitive assessment of multiple sclerosis (MS) patients is to find reliable measures utilizing diverse neuroimaging techniques. Moreover, especially relevant in the clinical environment is finding technical approaches that could be applied to individual participants and not only for group analysis. A 64-channel electroencephalographic recording (EEG) was made with thirty participants divided into three groups of equivalent size (N = 10) (healthy control, low-EDSS (1-2.5) and moderate-EDSS (4-6)). Correlation analysis was applied to multiple measures: behavior, neuropsychological tests (Paced Auditory Serial Addition Test, 3 seconds (PASAT-3s) and the Symbol Digit Modality Test (SDMT)), Expanded Disability Status Scale (EDSS), even-related potential (P3) and event-related desynchronization (ERD) parameters and the correlation scores between individual participant's P3/ERD maps and the healthy grand average P3/ERDmaps. Statistical analysis showed that diverse parameters exhibited significant correlations. A remarkable correlation was the moderate score found between SDMT and EDSS (r = -0.679, p = 0.0009). However, the strongest correlation was between the value of integrated measures (reaction time, P3 and ERD latency) and EDSS (r = 0.699, p = 0.0006). In regard to correlations for grand average maps between groups, the P3 component exhibited a lower score according to a more deteriorated condition (higher EDSS). In contrast, ERD maps remained stable with an increase of EDSS. Lastly, a Z-transformation of individual values of all variables included in the study exhibited heterogeneity in cognitive alterations in the multiple sclerosis participants.


Assuntos
Comportamento , Transtornos Cognitivos/fisiopatologia , Eletroencefalografia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Testes Neuropsicológicos , Adulto , Cognição , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/psicologia , Tempo de Reação , Classe Social
19.
Prog Brain Res ; 249: 227-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31325982

RESUMO

Acquired pendular nystagmus (APN) often occurs in association with the disorders affecting the visual system, such as multiple sclerosis (MS). The proposed mechanisms of APN in MS have been a delayed conduction of the visual information for ocular stabilization and unstable neural integrator for feedback controls. We determined the effects of visual inputs on the nystagmus intensity and the effects of saccades on phase shift of the nystagmus in a patient with monocular pendular nystagmus from MS. In this patient, (1) during binocular viewing in the light, the nystagmus was observed only in the eye with more severe visual loss, (2) the nystagmus disappeared in darkness, (3) monocular viewing with either eye markedly suppressed the nystagmus, (4) the nystagmus decreased when the visual inputs became less asymmetric between the eyes, and (5) saccades resulted in a phase shift of the nystagmus. From these results, we propose that the difference in the visual inputs between the eyes is responsible for monocular APN by disturbing visual integration and increasing instability of the feedback.


Assuntos
Modelos Neurológicos , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Nistagmo Patológico/fisiopatologia , Neurite Óptica/fisiopatologia , Transtornos da Visão/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/complicações , Nistagmo Patológico/etiologia , Neurite Óptica/complicações , Movimentos Sacádicos/fisiologia , Transtornos da Visão/etiologia , Visão Binocular/fisiologia , Visão Monocular/fisiologia
20.
Mult Scler Relat Disord ; 35: 83-85, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352181

RESUMO

BACKGROUND: Central nervous system involvement has been reported in different subtypes of Charcot-Marie-Tooth (CMT) diseases. The increasing number of cases with CMT and MS may provide further information about the common pathway of demyelination and MS pathogenesis. CASE PRESENTATION: We report the case of a 21-year-old woman with CMT1A and MS. Bilateral rest and intention tremor, steroid associated psychotic episodes, and severe disability at an early age were unexpected aspects of this case. CONCLUSION: PMP22, the target protein in CMT1A, shares partial homology with other CNS proteins. PMP22 gene might be relevant to a common pathway of the demyelinating process.


Assuntos
Doença de Charcot-Marie-Tooth/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Adulto , Doença de Charcot-Marie-Tooth/genética , Feminino , Humanos , Esclerose Múltipla Recidivante-Remitente/genética , Proteínas da Mielina , Adulto Jovem
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