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1.
Eur J Neurol ; 31(6): e16250, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38549186

RESUMO

BACKGROUND AND PURPOSE: Cladribine tablets, a purine analogue antimetabolite, offer a unique treatment regimen, involving short courses at the start of the first and second year, with no further treatment needed in years 3 and 4. However, comprehensive evidence regarding patient outcomes beyond the initial 24 months of cladribine treatment is limited. METHODS: This retrospective, multicenter study enrolled 204 patients with multiple sclerosis who had completed the 2-year course of cladribine treatment. The primary outcomes were therapeutic choices and clinical disease activity assessed by annualized relapse rate after the 2-year treatment course. RESULTS: A total of 204 patients were enrolled; most patients (75.4%) did not initiate new treatments in the 12 months postcladribine. The study found a significant reduction in annualized relapse rate at the 12-month follow-up after cladribine completion compared to the year prior to starting therapy (0.07 ± 0.25 vs. 0.82 ± 0.80, p < 0.001). Furthermore, patients with relapses during cladribine treatment were more likely to start new therapies, whereas older patients were less likely. The safety profile of cladribine was favorable, with lymphopenia being the primary registered adverse event. CONCLUSIONS: This study provides insights into therapeutic choices and disease activity following cladribine treatment. It highlights cladribine's effectiveness in reducing relapse rates and disability progression, reaffirming its favorable safety profile. Real-world data, aligned with previous reports, draw attention to ocrelizumab and natalizumab as common choices after cladribine. However, larger, prospective studies for validation and a more comprehensive understanding of cladribine's long-term impact are necessary.


Assuntos
Cladribina , Imunossupressores , Humanos , Cladribina/uso terapêutico , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Imunossupressores/uso terapêutico , Itália , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Resultado do Tratamento , Esclerose Múltipla/tratamento farmacológico
2.
Ann Neurol ; 91(4): 483-495, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35150168

RESUMO

OBJECTIVE: This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis. METHODS: Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease-modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated. RESULTS: A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease-modifying treatment exposure were independent predictors for long-term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long-term disability. INTERPRETATION: These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022;91:483-495.


Assuntos
Pessoas com Deficiência , Esclerose Múltipla , Criança , Progressão da Doença , Humanos , Masculino , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Prognóstico , Recidiva
3.
Mult Scler ; 29(10): 1337-1339, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37602442

RESUMO

BACKGROUND: The COVID-19 pandemic has underlined the need to evaluate cognitive profile via videoconferencing (teleneuropsychology, TeleNP) as a suitable alternative to face-to-face assessment (F-F). OBJECTIVE: To evaluate the feasibility and the reliability of Rao's Brief Repeatable Battery of Neuropsychological Tests (R-BRB) remote administration in people with multiple sclerosis (PwMS). METHODS: Sixty PwMS underwent R-BRB in two conditions: F-F and TeleNP, 1 month apart. RESULTS: Cognitive test performance was similar, regardless of the administration type, but visuospatial test performance was better in F-F. CONCLUSION: These data suggest that TeleNP is feasible and highly reliable in MS clinical practice.


Assuntos
COVID-19 , Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Pandemias , Reprodutibilidade dos Testes , Testes Neuropsicológicos , Comunicação por Videoconferência
4.
Brain ; 145(8): 2796-2805, 2022 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-35325059

RESUMO

Disability accrual in multiple sclerosis may occur as relapse-associated worsening or progression independent of relapse activity. The role of progression independent of relapse activity in early multiple sclerosis is yet to be established. The objective of this multicentre, observational, retrospective cohort study was to investigate the contribution of relapse-associated worsening and progression independent of relapse activity to confirmed disability accumulation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, assessed within one year from onset and with follow-up ≥5 years (n = 5169). Data were extracted from the Italian Multiple Sclerosis Register. Confirmed disability accumulation was defined by an increase in Expanded Disability Status Scale score confirmed at 6 months, and classified per temporal association with relapses. Factors associated with progression independent of relapse activity and relapse-associated worsening were assessed using multivariable Cox regression models. Over a follow-up period of 11.5 ± 5.5 years, progression independent of relapse activity occurred in 1427 (27.6%) and relapse-associated worsening in 922 (17.8%) patients. Progression independent of relapse activity was associated with older age at baseline [hazard ratio (HR) = 1.19; 95% confidence interval (CI) 1.13-1.25, P < 0.001], having a relapsing-remitting course at baseline (HR = 1.44; 95% CI 1.28-1.61, P < 0.001), longer disease duration at baseline (HR = 1.56; 95% CI 1.28-1.90, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.92; 95% CI 0.88-0.96, P < 0.001) and lower number of relapses before the event (HR = 0.76; 95% CI 0.73-0.80, P < 0.001). Relapse-associated worsening was associated with younger age at baseline (HR = 0.87; 95% CI 0.81-0.93, P < 0.001), having a relapsing-remitting course at baseline (HR = 1.55; 95% CI 1.35-1.79, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.94; 95% CI 0.89-0.99, P = 0.017) and a higher number of relapses before the event (HR = 1.04; 95% CI 1.01-1.07, P < 0.001). Longer exposure to disease-modifying drugs was associated with a lower risk of both progression independent of relapse activity and relapse-associated worsening (P < 0.001). This study provides evidence that in an early relapsing-onset multiple sclerosis cohort, progression independent of relapse activity was an important contributor to confirmed disability accumulation. Our findings indicate that insidious progression appears even in the earliest phases of the disease, suggesting that inflammation and neurodegeneration can represent a single disease continuum, in which age is one of the main determinants of disease phenomenology.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Doença Crônica , Estudos de Coortes , Progressão da Doença , Humanos , Recidiva , Estudos Retrospectivos
5.
Neurol Sci ; 44(1): 45-58, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36114980

RESUMO

OBJECTIVE: Multiple sclerosis (MS) is a chronic disease with different clinical courses and a tendency to worsening. The relapsing-remitting MS presents acute onset and relapses of neurological symptoms, followed by their remission. This form can convert to secondary progressive MS (SPMS) with irreversible neurological worsening and disability. The identification of signs, symptoms, markers of progression, and strategies to manage MS patients is mandatory to allow early identification of those at higher risk of conversion to SPMS, for prompt intervention to cope with the progression of the disease. METHODS: A panel of Italian experts from Southern Italy have reviewed the current knowledge on MS and its management and identified the crucial tools for SPMS recognition. RESULTS: More effective communication between patients and clinicians should be established, with the support of digital tools. Moreover, the improvement in the clinical use of biomarkers for progression (cellular structures and tissue organization, such as neurofilaments and chitinase 3-like 1, axonal and neurons density) and of instrumental analyses for recognition of whole-brain atrophy, chronic active lesions, spinal cord lesions and atrophy, and the improvement the combination of the Expanded Disability Status Scale and the evaluation of cognitive dysfunction are discussed. CONCLUSION: Given the availability of a pharmacological option, adequate education both for patients, regarding the evolution of the disease and the specific treatment, and for professionals, to allow more effective and sensitive communication and the best use of diagnostic and management tools, could represent a strategy to improve patient management and their quality of life.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Qualidade de Vida , Progressão da Doença , Recidiva Local de Neoplasia , Esclerose Múltipla Crônica Progressiva/diagnóstico , Itália , Atrofia , Atenção à Saúde
6.
Artigo em Inglês | MEDLINE | ID: mdl-36180219

RESUMO

OBJECTIVE: Assessing the risk of clinical and radiological reactivation during pregnancy and post partum in women with multiple sclerosis (MS) treated with natalizumab (NTZ) throughout pregnancy (LONG_EXP) compared with women interrupting treatment before (NO_EXP) and within >-30 days and ≤90 days from conception (SHORT_EXP), and describing newborns' outcomes. METHODS: Maternal clinical and radiological outcomes and obstetric and fetal outcomes were retrospectively collected and compared among groups (NO_EXP, SHORT_EXP, LONG_EXP). Predictors of clinical and radiological reactivation were investigated through univariable and multivariable analysis. RESULTS: 170 eligible pregnancies from 163 women referring to 29 Italian MS centres were included. Annualised relapse rate (ARR) was significantly lower in LONG_EXP (n=66, 0.02 (0.001-0.09)) compared with NO_EXP (n=31, 0.43 (0.21-0.75), p=0.002) and SHORT_EXP (n=73, 0.46 (0.30-0.66), p=0.0004) during pregnancy, and in LONG_EXP (0.12 (0.05-0.24)) compared with SHORT_EXP (0.30 (0.17-0.50), p=0.008) during post partum. Gadolinium-enhancing (Gd+) lesions were less frequent in LONG_EXP (n=6/50, 2.00%) compared with NO_EXP (n=9/21, 42.86%) and SHORT_EXP after delivery (n=17/49, 34.69%, p=0.010).Delaying NTZ resumption after delivery significantly increased the risk of relapses (OR=1.29 (95% CI 1.07 to 1.57), p=0.009) and Gd+ lesions (OR=1.49 (95% CI 1.17 to 1.89, p=0.001). Newborns' weight, length, head circumference and gestational age did not differ among groups after adjusting for confounders. Anaemia was tracked in 4/69 LONG_EXP newborns. Congenital anomaly rate was within the expected range for the untreated MS population. CONCLUSIONS: Our findings indicate that in women with MS treated with NTZ before conception, continuation of NTZ throughout pregnancy and its early resumption after delivery mitigate the risk of clinical and radiological reactivation. This approach has no major impact on newborns' outcomes.

7.
Mult Scler ; 28(1): 93-101, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33855897

RESUMO

OBJECTIVES: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. METHODS: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. RESULTS: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. DISCUSSION AND CONCLUSION: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Anticorpos Monoclonais Humanizados , Cloridrato de Fingolimode/uso terapêutico , Humanos , Imunossupressores , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab , Estudos Retrospectivos
8.
Mult Scler ; 28(14): 2243-2252, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35971322

RESUMO

BACKGROUND: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. OBJECTIVES: To compare diagnostic performances of two different data-driven SPMS definitions. METHODS: Data-driven SPMS definitions based on a version of Lorscheider's algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist's definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). RESULTS: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). CONCLUSION: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist's definition and the global accuracy of DDA seems to be higher than the EXPAND definition.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Área Sob a Curva , Esclerose Múltipla Crônica Progressiva/diagnóstico , Esclerose Múltipla Recidivante-Remitente/diagnóstico
9.
Eur J Neurol ; 29(1): 257-266, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34558755

RESUMO

BACKGROUND AND PURPOSE: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. METHODS: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. RESULTS: We studied 322 patients (mean age 36.8 years, median EDSS score 3, median follow-up 1.94 years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p < 0.001). The number of previous-year relapses was associated with alemtuzumab ARR (adjusted risk ratio [RR] 1.38, p = 0.009). Progression-free survival was 94.5% after 1 year, and 89.2% after 2 years of alemtuzumab treatment. EDSS score improvement occurred in 13.5% after 1 year, and 20.6% after 2 years. Re-baselining patients after 6 months of alemtuzumab treatment, led to no evidence of disease activity status in 71.6% after 1 year and 58.9% after 2 years. CONCLUSIONS: Alemtuzumab decreases ARR independent of previous therapy, including patients with disease activity during natalizumab treatment. Overall, 90% of patients showed no disease progression, and 20% an improvement after 2 years of alemtuzumab.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Adulto , Alemtuzumab/uso terapêutico , Cloridrato de Fingolimode/uso terapêutico , Acetato de Glatiramer/uso terapêutico , Humanos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Estudos Retrospectivos
10.
Artigo em Inglês | MEDLINE | ID: mdl-36481657

RESUMO

BACKGROUND: Therapeutic Plasmapheresis (TP) is an extracorporeal therapy that allows the removal of pathogens from plasma. The role of TP in immuno-mediated diseases and toxic conditions has been of interest for decades. SUMMARY: We reviewed the recent literature on the application and the optimal choice of TP technique ranging from Plasma Exchange, Double Filtration Plasmapheresis, Rheopheresis, Immunoadsorptions and Lipidoapheresis. In addition, we report our experience in the application of TP for various diseases ranging in different medical specialties, following the American Society for Apheresis (ASFA) recommendations. KEY MESSAGES: Overall patients receiving TP showed an improvement in clinical and laboratory parameters. Our review and single center experience suggest a benefit of the application of TP in multiple clinical disciplines.

11.
Neurol Sci ; 43(4): 2601-2609, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34561786

RESUMO

INTRODUCTION: Blood coagulation constituents might exert immunomodulatory functions in the CNS and may trigger neuroinflammation and demyelination. We evaluated whether particular single-nucleotide polymorphisms (SNPs), thought to be involved in fibrinogen-mediated hemostatic pathways, are overrepresented in patients with MS compared with controls. METHODS: The case-control study consisted of 119 MS patients recruited consecutively at our clinic, and 68 healthy controls. Afterwards, we created a cumulative genetic risk score (CGRS) which included the 5 selected hemostatic risk alleles (Beta-Fibrinogen 455G/A, Glycoprotein IIIa P1A2, Factor V Leiden, Factor V H2R, and Prothrombin 20210G/A). Multivariate ordinal logistic regression and multivariate multinomial logistic regression were applied to evaluate the effect of CGRS on MS susceptibility. RESULTS: The FGB 455 G/A and Factor V H1299R variants might be associated with MS status, in the recessive and dominant model, respectively. A cumulative association of the five SNPs investigated with the disease was observed. DISCUSSION: We found that MS patients carried more pro-hemostatic variants than healthy controls. An increasing number of unfavorable alleles might increase the likelihood of being in the MS group, in the cumulative analysis. Our findings encourage to evaluating these variants in a larger population-based cohort.


Assuntos
Hemostáticos , Esclerose Múltipla , Estudos de Casos e Controles , Fibrinogênio/genética , Predisposição Genética para Doença/genética , Humanos , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética
12.
Neurol Sci ; 43(11): 6415-6423, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35781765

RESUMO

BACKGROUND: Natalizumab (NAT) has a strong impact on disease activity of aggressive pediatric multiple sclerosis (MS), with no difference in safety profile compared to adult MS. However, available data are limited by short follow-up. Our aim was to report long-term follow-up data (up to 11 years) of a large Italian pediatric MS cohort treated with NAT. MATERIALS AND METHODS: We retrospectively collected data of pediatric MS patients treated with NAT included in a previous study and prospectively followed in Italian MS centers. We compared disease activity pre, during, and post-NAT and we performed survival analyses of time to evidence of disease activity (EDA) during NAT, time to reach EDA post-NAT, and time to NAT discontinuation. RESULTS: Ninety-two patients were included from 19 MS centers in Italy. At NAT initiation, cohort's characteristics were as follows: 55 females; 14.7 ± 2.4 (mean ± SD) years of age; 34 naïve to disease modifying therapies; 1-year pre-NAT annualized relapse rate (ARR): 2.2 ± 1.2; EDSS (median [IQR]): 2.5 [2.0-3.0]; gadolinium-enhancing lesions: 2 [1-5]; 41 JCV positives. During NAT treatment (61.9 ± 35.2 mean infusions), ARR lowered to 0.08 ± 0.23 (p < 0.001), EDSS score to 1.5 [1.0-2.5] at last infusion (p < 0.001), and 51% patients had EDA (21% after 6 months of rebaseline). No serious adverse events were reported. Forty-nine patients discontinued NAT, mainly due to PML concern; the majority (29/49) had disease reactivation in the subsequent 12 months, of which three with a clinical rebound. CONCLUSION: NAT treatment maintains its high efficacy for a long time in pediatric MS patients, with no new safety issues.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Adulto , Feminino , Humanos , Criança , Natalizumab/efeitos adversos , Seguimentos , Estudos Retrospectivos , Esclerose Múltipla/tratamento farmacológico , Recidiva , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Fatores Imunológicos/efeitos adversos
13.
Neurol Sci ; 43(2): 1007-1014, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34142263

RESUMO

OBJECTIVES: To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). MATERIALS AND METHODS: This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. RESULTS: Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1-7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01-1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04-1.17, p = 0.002) were associated with discrepancies between GM® and routine clinical scoring. CONCLUSION: GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.


Assuntos
Esclerose Múltipla , Ferramenta de Busca , Estudos Transversais , Avaliação da Deficiência , Fadiga/diagnóstico , Fadiga/epidemiologia , Humanos , Esclerose Múltipla/diagnóstico
14.
Mult Scler ; 27(3): 430-438, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33210986

RESUMO

BACKGROUND: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. OBJECTIVE: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). METHODS: Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. RESULTS: SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. CONCLUSION: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Progressão da Doença , Humanos , Esclerose Múltipla Crônica Progressiva/epidemiologia , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Recidiva , Fatores de Risco
15.
Brain ; 143(10): 3013-3024, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32935843

RESUMO

An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18-49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% confidence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5-17.9) for paediatric-onset and 6.3 (4.9-8.0) for adult-onset, P < 0.0001] showing a trend in late-onset patients [adjusted hazard ratio = 1.9 (0.9-4.1), P = 0.07]. These results were confirmed for a sustained EDSS score of 4.0. We also found that relapses were a risk factor for 12-month confirmed disability worsening in all three cohorts, and female sex exerted a protective role in the late-onset cohort. This study provides evidence that sustained exposure to disease-modifying drugs decreases the risk of disability accumulation, seemingly in a dose-dependent manner. It confirms that the effectiveness of disease-modifying drugs is lower in late-onset patients, although still detectable.


Assuntos
Antirreumáticos/uso terapêutico , Pessoas com Deficiência , Progressão da Doença , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos
16.
J Stroke Cerebrovasc Dis ; 30(6): 105744, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33813081

RESUMO

BACKGROUND AND OBJECTIVES: Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder caused by pathogenic variants in the ABCC6 gene. The phenotypic spectrum of PXE is highly variable and includes principally three major features: skin lesions, eye and vascular manifestations, while brain manifestations are less common. To date about 400 different PXE associated variants in ABCC6 gene are described without any evident genotype-phenotype correlation. Herein, we report the clinical and molecular findings of a large PXE family with clinical and genetic intra-familial variability with significant cerebrovascular involvement. METHODS: The analysis of the ABCC6 gene was performed in the proband and her familiars for the definition of genetic background. Then, in order to determine why some affected individuals had more prominent brain involvement, we investigated classic thrombophilic gene variants. RESULTS: Molecular findings disclosed two different ABCC6 mutations, i.e., the recurrent p.(Arg518Gln) and the novel p.(Val1285Met) missense substitution responsible of a pseudo-dominant inheritance. The study of thrombophilic gene variants revealed the presence of 4G/4G SERPINE1 genotype in the proband and in her father, which both developed ischemic stroke. The proband carried also the C677T variant the MTHFR gene. CONCLUSION: We argue, for the first time, that the 4G/4G SERPINE1 genotype could represent an additional risk factor in PXE for developing ischemic stroke, which adds up to the already known predisposing conditions. Therapeutic implications are discussed, we also advise that PXE patients should be adequately screened for cerebral vasculopathy, even more if familial history is suggestive of brain complications.


Assuntos
Heterogeneidade Genética , AVC Isquêmico/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Pseudoxantoma Elástico/genética , Trombofilia/genética , Adulto , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Masculino , Linhagem , Pseudoxantoma Elástico/complicações , Pseudoxantoma Elástico/diagnóstico , Medição de Risco , Fatores de Risco , Trombofilia/sangue , Trombofilia/complicações , Trombofilia/diagnóstico
17.
J Neurol Neurosurg Psychiatry ; 91(9): 914-920, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32661083

RESUMO

INTRODUCTION: Delta-δ-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray is used as an add-on therapy option for moderate to severe multiple sclerosis (MS) spasticity resistant to other medications. Aims of this study were to provide real-life data on long-term clinical outcomes in a large population of Italian patients treated with THC:CBD and to evaluate predictors of THC:CBD therapy continuation. MATERIALS AND METHODS: This prospective observational multicentre Italian study screened all patients with MS consecutively included in the Agenzia Italiana del Farmaco e-registry at the start of THC:CBD treatment (baseline), after 4 weeks (T1), 12±3 weeks (T2), 24±3 weeks (T3), 48±3 weeks (T4) and 72±3 weeks (T5) from baseline. RESULTS: A total of 1845 patients were recruited from 32 MS Italian centres. At T1, 1502 (81.4%) of patients reached a Numerical Rating Scale (NRS) improvement of ≥20%, with an NRS reduction of 26.9% at T1 and of 34.4% at T5. At T5, 725 patients (48.3% of 1502) discontinued treatment with highest discontinuation rate at T2 and T3. Daily number of puffs was generally stable through the observation period. The multivariate analysis showed that higher NRS scores at baseline (OR 2.28, 95% CI 1.15 to 6.36, p<0.01) and higher differences of NRS between T0 and T1 (OR 2.11, 95% CI 1.08 to 8.26, p<0.05) were associated with an increased probability to continue therapy after 18 months. DISCUSSION: THC:CBD effects were sustained for 18 months with a relatively stable number of puffs per day. About 50% of patients abandoned THC:CBD therapy for loss of efficacy or adverse events.


Assuntos
Canabidiol/uso terapêutico , Dronabinol/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Suspensão de Tratamento/estatística & dados numéricos
18.
Ann Neurol ; 81(5): 729-739, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28439957

RESUMO

OBJECTIVE: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients. METHODS: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data. RESULTS: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06-1.55; 1.42, 1.10-1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60-0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42-0.83; 0.75, 0.71-0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46-7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening. INTERPRETATION: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729-739.


Assuntos
Doenças Desmielinizantes/diagnóstico , Progressão da Doença , Esclerose Múltipla/diagnóstico , Sistema de Registros , Adolescente , Idade de Início , Criança , Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/fisiopatologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
19.
Mult Scler ; 23(9): 1289-1296, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27811338

RESUMO

OBJECTIVE: Despite cognitive tests have been validated in multiple sclerosis (MS), a neuropsychological evaluation is not implemented in the Expanded Disability Status Scale (EDSS) scoring. METHODS: We used the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and orientation tests (OTs) to measure the cerebral functional system (CFS) score and to evaluate its impact on the EDSS. We compared EDSS calculated as usual (Native-EDSS) and after the use of the BICAMS and OT (NPS-EDSS). RESULTS: We tested 604 MS patients with BICAMS, OTs, and EDSS. In all, 384 patients (63.6%) had at least one altered test at the BICAMS. Older age, lower education, higher Native-EDSS, and male gender were independently associated with at least one impaired BICAMS test. Native-EDSS was different from NPS-EDSS (-0.112; p < 0.001) in 99 patients (16%). When considering patients with a Native-EDSS ⩽ 4.0, the proportion of miscalculated EDSS was 25%. CONCLUSION: The use of brief neuropsychological tests leads to a more accurate CFS assessment in two-thirds of MS patients, and a more accurate EDSS calculation in 25% of patients with a score ⩽4.0. This may help clinicians to better recognize cognitive impairment in everyday clinical practice, especially in the case of isolated cognitive worsening.


Assuntos
Disfunção Cognitiva/diagnóstico , Esclerose Múltipla/diagnóstico , Exame Neurológico/métodos , Testes Neuropsicológicos , Orientação/fisiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Exame Neurológico/normas , Estudos Retrospectivos , Adulto Jovem
20.
BMC Neurol ; 17(1): 156, 2017 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-28793876

RESUMO

BACKGROUND: Patients with multiple sclerosis (MS) receiving long-term, subcutaneous interferon ß-1b (IFN ß-1b; Extavia®) often experience injection-site reactions and injection-site pain, which together with other side-effects (such as flu-like symptoms) result in suboptimal treatment compliance/adherence. The EXCHANGE study evaluated patient satisfaction with IFN ß-1b treatment, administered using ExtaviPro™ 30G, a new auto-injector, in a real-world setting. METHODS: This 26-week, open-label, prospective, non-interventional, observational, multi-country multi-centre study enrolled patients with MS who had been treated with IFN ß-1b or other disease-modifying therapies with a self-administered auto-injector for ≥3 months and who were planned to switch to IFN ß-1b treatment administered using ExtaviPro™ 30G as part of routine clinical care. Patient-reported outcomes included overall patient satisfaction (primary outcome) and satisfaction associated with treatment effectiveness, convenience and side-effects, assessed using Treatment Satisfaction Questionnaire for Medication (TSQM)-14. The changes in TSQM scores from baseline to Week 26 were reported. All data were analysed using SAS statistical software (version 9.4). RESULTS: Of the 336 patients enrolled, 324 were included in the analysis. At baseline, mean ± standard deviation (SD) age of patients was 41.8 ± 11.3 years and 68.2% were women. The mean ± SD of MS disease duration was 6.9 ± 6.6 years, and the majority of patients (94.1%) had relapsing-remitting MS. The mean ± SD of TSQM score for overall patient satisfaction at Week 26 was 75.6 ± 16.46 (baseline, 73.0 ± 17.14; p = 0.0342). The mean ± SD of TSQM subscale scores for patient satisfaction with effectiveness, side-effects and convenience were 75.0 ± 18.65 (baseline, 71.6 ± 19.45; p = 0.0356), 88.5 ± 18.98 (baseline, 82.7 ± 22.93; p = 0.0002) and 77.6 ± 16.72 (baseline, 71.1 ± 17.53; p < 0.0001), respectively. CONCLUSION: The results from this real-world study suggest that administering IFN ß-1b with the new ExtaviPro™ auto-injector significantly improves overall patient satisfaction, including satisfaction associated with effectiveness, side-effects and convenience in MS patients.


Assuntos
Interferon beta-1b/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Satisfação do Paciente , Adulto , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Resultado do Tratamento
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