RESUMO
Over the past decades, several effective disease-modifying therapies have been approved for the treatment of multiple sclerosis (MS); however, achieving long-term disease remission remains challenging, particularly for patients with aggressive forms of MS. Intense immunosuppression followed by hematopoietic stem cell transplantation (HSCT) has been increasingly explored as a treatment strategy for aggressive MS. To date, more than 1800 MS patients have undergone HSCT worldwide. In this chapter, we provide a brief overview of the HSCT procedure, with a special focus on the unique considerations for transplanting MS patients (such as fertility preservation, prior therapy washout, and posttransplant monitoring). We also discuss the main evidence of efficacy and safety of the procedure in this context, as well as present preliminary data on the impact of HSCT on cerebrospinal fluid findings, magnetic resonance imaging metrics, and novel serum biomarkers of neurodegeneration and demyelination. In addition, we provide recommendations for patient selection from international guidelines.
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Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Esclerose Múltipla/terapiaRESUMO
The use of hematopoietic stem cell transplantation (HSCT) as a treatment option for severe autoimmune diseases originated from animal studies, with promising results in human patients reported through clinical responses seen in individuals who underwent HSCT for other reasons. Currently, over 3800 HSCT procedures have been performed specifically for autoimmune disorders and the procedure has become a standard of care for conditions such as multiple sclerosis and systemic sclerosis. Despite the growing interest among the neurology community in using HSCT to treat refractory autoimmune disorders, several obstacles must still be overcome for the procedure to become widely accepted. These include increasing the safety of the procedure, determining the most effective conditioning regimen, fostering collaboration between neurology and hematology teams, and providing robust phase III study data to demonstrate the superiority of HSCT over standard immunotherapy. This Handbook aims to provide a valuable resource for all those involved in the care of patients undergoing HSCT, and we hope it will contribute to the efforts to find the correct placement of HSCT in the therapeutic strategy of the treatment of autoimmune disorders of the nervous system.
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Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Nervoso , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Doenças do Sistema Nervoso/terapia , AnimaisRESUMO
BACKGROUND AND OBJECTIVES: Uncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study, we compared the effect of AHSCT with that of other anti-inflammatory disease-modifying therapies (DMTs) on long-term disability worsening in active SPMS. METHODS: We collected data from the Italian Bone Marrow Transplantation Study Group and the Italian Multiple Sclerosis Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-month confirmed disability progression (CDP) according to the Expanded Disability Status Scale (EDSS) score. Key secondary endpoints were the EDSS time trend after treatment start and the prevalence of disability improvement over time. Time to first CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time × treatment group interaction was used to assess the longitudinal EDSS time trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve. RESULTS: Seventy-nine AHSCT-treated patients and 1975 patients treated with other DMTs (beta interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, and alemtuzumab) were matched to reduce treatment selection bias using propensity score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (hazard ratio [HR] = 0.50; 95% CI = 0.31-0.81; p = 0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time trend over 10 years was higher in patients treated with other DMTs than in AHSCT-treated patients (+0.157 EDSS points per year compared with -0.013 EDSS points per year; interaction p < 0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant vs 4.6% of patients treated by other DMTs (p < 0.001). DISCUSSION: The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared with standard immunotherapy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to CDP compared with other DMTs.
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Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Acetato de Glatiramer , Cloridrato de Fingolimode , Esclerose Múltipla Recidivante-Remitente/terapiaRESUMO
BACKGROUND: Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their possible role in MS. OBJECTIVE: To evaluate the correlation between innate and adaptive immune cell subsets and disease activity in MS in the context of treatment with alemtuzumab. METHODS: A two-center observational cohort of patients treated with alemtuzumab underwent immune profiling of T, B, and natural killer (NK) cells, biomarker, clinical and radiological follow-up. RESULTS: After treatment, the percentage of NK and B cells increased; NK, T- and B-cell populations underwent a profound rearrangement. Within the effector T-cell compartment, treatment led to a transient decrease, followed by an increase, of T-helper 1 cells, and to a transient decrease of T-helper 17 cells. Within the T-regulatory compartment, naïve T-regulatory cells increased. Within the B-cell compartment, memory B cells and mature B cells decreased, whereas transitional B cells increased. Within the NK cell compartment, CD56bright NK cells increased. Subjects without disease activity had a greater decrease in serum NfL and greater NK cell/CD3+ T cell ratio. NK cell numbers at baseline and after treatment influenced reconstitution of T and B cells, being inversely correlated with the reconstitution of proinflammatory CD3+ T cells and mature B cells, and directly correlated to the increase in transitional B cells. CONCLUSIONS: The results of this study provide novel evidence that NK cells influence reconstitution of adaptive immune cells upon alemtuzumab and that patients with a successful response to alemtuzumab have an early immune reconstitution dominated by NK cells.
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Alemtuzumab/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Células Matadoras Naturais/imunologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Itália , Estudos Longitudinais , Masculino , Esclerose Múltipla Recidivante-Remitente/imunologiaRESUMO
BACKGROUND: Natalizumab is a monoclonal antibody approved for the treatment of patients with relapsing-remitting multiple sclerosis. According to the current clinical recommendations, its use during pregnancy should be carefully evaluated only in women with highly active disease who plan a pregnancy or have an unplanned pregnancy, after accurate counseling about eventual maternal disease relapse due to therapy suspension. CASE PRESENTATION: This brief case report describes a case of documented anemia that we observed in a newborn whose mother with relapsing-remitting multiple sclerosis was treated with an extended dosing protocol of natalizumab throughout pregnancy. The newborn received the infusion of erythropoietin every seven days from the fortieth day of life; subsequently, the status of anemia underwent clinical resolution. CONCLUSIONS: This case report confirmed that natalizumab can cause disorders of hematopoiesis, including anemia, thrombocytopenia, or pancytopenia, in newborns of patients treated during pregnancy. A multidisciplinary team, including experienced pediatricians and pediatric hematologists, has a critical role in managing newborns delivered by women, being treated with natalizumab for treating relapsing-remitting multiple sclerosis during pregnancy.
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Anemia Neonatal/tratamento farmacológico , Eritropoetina/uso terapêutico , Fatores Imunológicos/efeitos adversos , Troca Materno-Fetal , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos , Anemia Neonatal/induzido quimicamente , Feminino , Humanos , Recém-Nascido , Infusões Intravenosas , GravidezRESUMO
BACKGROUND: Assessment of nigrostriatal degeneration is a key element to discriminate between dementia with Lewy bodies (DLB) and Alzheimer disease (AD), and it is often evaluated using ioflupane (123I-FP-CIT) single-photon emission computed tomography (SPECT). Given the limited availability of 123I-FP-CIT SPECT, we evaluated if a mask-based approach to nigroputaminal magnetic resonance imaging (MRI) diffusion-weighted tractography could be able to capture microstructural changes reflecting nigroputaminal degeneration in DLB. METHODS: A nigroputaminal bundle mask was delineated on 12 healthy volunteers (HV) and applied to MRI diffusion-weighted data of 18 subjects with DLB, 21 subjects with AD and another group of 12 HV. The correlation between nigroputaminal fractional anisotropy (FA) values and 123I-FP-CIT SPECT findings was investigated. Shapiro-Wilk, ANOVA, ANCOVA, and parametric correlation statistics as well as receiver operating characteristic (ROC) analysis were used. RESULTS: DLB patients showed a higher nigroputaminal FA values compared with both AD and HV-controls groups (p = 0.001 for both comparisons), while no difference was observed between HV-controls and AD groups (p = 0.450); at ROC analysis, the area under the curve for the discriminating DLB and AD subjects was 0.820; FA values correlated with 123I-FP-CIT values (on the left, r = -0.670; on the right, r = -720). No significant differences were observed for the FA of the corticospinal tract across the three groups (p = 0.740). CONCLUSIONS: In DLB, nigroputaminal degeneration could be reliably assessed on MRI diffusion scans using a mask of nigroputaminal bundle trajectory. Nigroputaminal FA in DLB patients correlated with 123I-FP-CIT values data may allow to differentiate these patients from AD patients and HV-controls.
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Imagem de Tensor de Difusão/métodos , Doença por Corpos de Lewy/diagnóstico por imagem , Putamen/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Putamen/patologia , Substância Negra/patologia , TropanosRESUMO
Background/Objective. Position sense, defined as the ability to identify joint and limb position in space, is crucial for balance and gait but has received limited attention in patients with multiple sclerosis (MS). We investigated lower limb position sense deficits, their neural correlates, and their effects on standing balance in patients with early MS. Methods. A total of 24 patients with early relapsing-remitting MS and 24 healthy controls performed ipsilateral and contralateral matching tasks with the right foot during functional magnetic resonance imaging. Corpus callosum (CC) integrity was estimated with diffusion tensor imaging. Patients also underwent an assessment of balance during quiet standing. We investigated differences between the 2 groups and the relations among proprioceptive errors, balance performance, and functional/structural correlates. Results. During the contralateral matching task, patients demonstrated a higher matching error than controls, which correlated with the microstructural damage of the CC and with balance ability. In contrast, during the ipsilateral task, the 2 groups showed a similar matching performance, but patients displayed a functional reorganization involving the parietal areas. Neural activity in the frontoparietal regions correlated with the performance during both proprioceptive matching tasks and quiet standing. Conclusion. Patients with early MS had subtle, clinically undetectable, position sense deficits at the lower limbs that, nevertheless, affected standing balance. Functional changes allowed correct proprioception processing during the ipsilateral matching task but not during the more demanding bilateral task, possibly because of damage to the CC. These findings provide new insights into the mechanisms underlying disability in MS and could influence the design of neurorehabilitation protocols.
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Córtex Cerebral/fisiopatologia , Corpo Caloso/patologia , Extremidade Inferior/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Plasticidade Neuronal/fisiologia , Propriocepção/fisiologia , Desempenho Psicomotor/fisiologia , Transtornos de Sensação/fisiopatologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Equilíbrio Postural/fisiologia , Estudos Prospectivos , Transtornos de Sensação/etiologiaRESUMO
Objective: To analyze MRI images in patients with MS who experienced worsening of neurologic status (WNS) after stopping fingolimod (FTY). Methods: In this retrospective study, demographic, clinical, and radiologic data of patients with MS who experienced WNS after stopping FTY were retrospectively collected. We introduced the "δExpanded Disability Status Scale (EDSS)-ratio" to identify patients who, after FTY withdrawal, showed an inflammatory flare-up exceeding the highest lifetime disease activity level. Patients with δEDSS-ratio > 1 were enrolled in the study. Results: Eight patients were identified. The mean (SD) age of the 8 (7 female) patients was 35.3 (4.9) years. The mean FTY treatment duration was 3.1 (0.8) years. The mean FTY discontinuation-WNS interval was 4 (0.9) months. The 4 patients with δEDSS-ratio ≥ 2 developed severe monophasic WNS (EDSS score above 8.5), characterized by clinical features and MRI findings not typical of MS, which we classified as "tumefactive demyelination pattern" (TDL) and "Punctuated pattern" (PL). Conversely, patients whose δEDSS-ratio was between 1 and 2 had clinical features and brain MRI compatible with a more typical, even if aggressive, MS relapse. In patients with TDL and PL, the flare-up of inflammatory activity led to severe tissue damage resulting in T2 but also T1 lesion volume increase at 6-month follow-up. Conclusions: Peculiar MRI features (TDL and PL), different from a typical MS flare-up, might occur in some patients who experienced WNS after stopping FTY. Further studies, also involving immunologic biomarkers, are necessary to investigate TDL or PL pathophysiology.
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Cloridrato de Fingolimode/efeitos adversos , Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Exacerbação dos Sintomas , Adulto , Avaliação da Deficiência , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos RetrospectivosRESUMO
The aim of this work was to investigate changes in motor performance and in the brain activation pattern during finger movements, following upper limb motor training in multiple sclerosis. Thirty people with multiple sclerosis with mild upper limb sensorimotor deficits were randomly allocated to one of two groups: the experimental group (nâ¯=â¯15) received an upper limb treatment based on voluntary task-oriented movements; the control group (nâ¯=â¯15) underwent passive mobilization of shoulder, elbow, wrist and fingers. All participants completed three treatment sessions per week for eight weeks. Before and after the intervention, all participants were evaluated for motor performance by means of Action Research Arm Test, Nine Hole Peg Test, and grip strength by a dynamometer, and for brain activations by functional magnetic resonance imaging during right finger opposition movements. Similar effects on motor performance were found in the two groups. A significant improvement with time was found in both groups at NHPT and in GRIP strength; a similar trend was found at ARAT. However, only the experimental group showed increased lateralization towards more normal brain activation following treatment, with activation clusters mainly located in the left brain hemisphere and right cerebellum. In conclusion, both active and passive interventions were effective in improving motor performance. However, only the treatment based on voluntary task-oriented movements could induce changes in brain activity that may have reflected skill acquisition by the right hand, reducing the activation of compensatory areas and decreasing brain resource demand.
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Encéfalo/fisiologia , Terapia por Exercício/métodos , Destreza Motora/fisiologia , Esclerose Múltipla/reabilitação , Desempenho Psicomotor/fisiologia , Extremidade Superior/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagemRESUMO
OBJECTIVE: To evaluate in clinically isolated syndrome (CIS) and migraine with aura (MA) how the number of periventricular lesions (PVLs) detected at MRI influences diagnostic performance when the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) or the 2017 revised criteria are applied. METHODS: In this retrospective study, white matter hyperintensities (WMH) of 84 patients with MA and 79 patients with CIS were assessed using manual segmentation technique. Lesion probability maps (LPMs) and voxel-wise analysis of lesion distribution by diagnosis were obtained. Furthermore, we performed a logistic regression analysis based on lesion locations and volumes. RESULTS: Compared to patients with MA, patients with CIS showed a significant overall higher T2 WMH mean number and volume (17.9 ± 16.9 vs 6.2 ± 11.9 and 3.1 ± 4.2 vs 0.3 ± 0.6 mL; p < 0.0001) and a significantly higher T2 WMH mean number in infratentorial, periventricular, and juxtacortical areas (p < 0.0001). LPMs identified the periventricular regions as the sites with the highest probability of detecting T2 WMH in patients with CIS. Voxel-wise analysis of lesion distribution by diagnosis revealed a statistically significant association exclusively between the diagnosis of CIS and the PVLs. MAGNIMS criteria demonstrated the highest specificity in differentiating patients with CIS from patients with MA (100% vs 87%) against a predictable lower sensitivity (63% vs 72%). CONCLUSIONS: PVLs play a key role in the differential diagnosis between MA and CIS, particularly when there are more than 3. Future studies on multiple sclerosis criteria might reconsider the 3 PVLs to minimize the risk of misdiagnosis. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the presence at least 3 PVLs increases the specificity in distinguishing MA from CIS.
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Leucomalácia Periventricular/diagnóstico por imagem , Enxaqueca com Aura/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Adolescente , Adulto , Idoso , Mapeamento Encefálico , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Substância Branca/diagnóstico por imagem , Adulto JovemAssuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Autoanticorpos , Transtornos Mentais , Receptores de N-Metil-D-Aspartato/imunologia , Adolescente , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/sangue , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/líquido cefalorraquidiano , Transtornos Mentais/fisiopatologia , Adulto JovemRESUMO
PURPOSE: We performed a pharmacovigilance study of 10 drugs used in patients with relapsing-remitting multiple sclerosis (RR-MS). Our aim was to provide an overview of the safety of these drugs by the evaluation of reported expected and unexpected adverse reactions. PATIENTS AND METHODS: We collected and analyzed adverse drug reactions from RR-MS patients belonging to four hospitals in three Italian regions, for a period of 24 months. RESULTS: We received a total of 411 adverse reactions, of which 84.18% were expected and only 15.82% were unexpected. We found no correlation between the number of reported adverse reactions and the route of administration (injectable/intravenous drugs N=224, oral drugs N=187). However, oral agents have caused a greater number of unexpected moderate-to-severe adverse reactions while, in injectable and infusion therapies, they have been evaluated as mild-moderate adverse reactions. CONCLUSION: Our results underscore the importance of monitoring the safety profile of multiple sclerosis therapies, with particular attention to oral agents that have been introduced later in the clinical practice.
RESUMO
Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right-handed and right-footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching.
Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Pé/fisiologia , Imageamento por Ressonância Magnética/métodos , Propriocepção/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Análise de Variância , Feminino , Pé/inervação , Lateralidade Funcional , Mãos/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Movimento , Oxigênio/sangue , Postura , Adulto JovemRESUMO
BACKGROUND: The use of composite magnetic resonance imaging (MRI) measures has been suggested to better explain disability in patients with multiple sclerosis (MS). However, little is known about the utility of composite scores at the earliest stages of the disease. OBJECTIVE: To investigate whether, in patients with clinically isolated syndrome (CIS), a composite MRI measure, rather than the single metrics, would explain conversion to MS and would better correlate with disability at baseline and at 1 year of follow-up. METHODS: Corticospinal tract (CST), corpus callosum (CC) and optic radiation (OR) volume, fractional anisotropy (FA), and mean diffusivity (MD) values were measured in 27 CIS patients and 24 healthy controls (HCs). Z-scores of FA, MD, and tract volume measures were calculated in patients, based on the corresponding measures obtained from HCs, and then combined in a composite score for each tract. Correlations between Z-scores at baseline and both the Expanded Disability Status Scale (EDSS) at baseline and at follow-up (FU-EDSS) were investigated. RESULTS: Only CST, CC, and OR composite scores as well as the CST volume were significantly associated with FU-EDSS ( p = 0.005, p = 0.007, p = 0.020, and p = 0.010, respectively). CONCLUSION: The combination of MRI measures rather than the individual metrics better captured the association between tissue damage in both the CC, OR and CST and short-term follow-up disability.
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Avaliação da Deficiência , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Adolescente , Adulto , Mapeamento Encefálico , Estudos de Coortes , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Recidiva , Estatísticas não Paramétricas , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto JovemRESUMO
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from â¼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4-5 years in 70-80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs.
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Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/normas , HumanosRESUMO
Delirium is an acute neuropsychiatric syndrome, very common in hospitalized people with medical and neurological conditions. The identification of delirium after stroke is not an easy task and validated psychometric instruments are needed to correctly identify it. We decided to verify if (1) formal training in DSM-V criteria is needed to correctly identify post-stroke delirium, (2) if the use of a brief psychometric instrument such as 4AT improves its identification, (3) the applicability of these scales in the stroke setting. In the first phase of this study we retrospectively studied 102 acute stroke patients in Stroke Units of San Martino Hospital (Genova, Italy) to evaluate delirium with clinical criteria, first by a neurologist without a formal training in DSM-V criteria and after training. Then, we enrolled 100 new acute stroke patients who underwent screening for delirium using 4AT scale and DSM-V criteria. In the first phase, DSM-V criteria training significantly increased the ability to capture delirium (5 vs. 15%). In the second phase, the 4AT was used for delirium screening revealing a 52% of cases of delirium, the same observed by the consensus diagnosis of two senior neurologists (that was 50%). In the second phase, the use of 4AT scale allowed to capture post-stroke delirium as well as the consensus diagnosis by two neurologists. The identification of post-stroke delirium is not an easy task and requires both formal training in DSM-V criteria as well as the application of brief scales, such as the 4AT.
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Delírio/diagnóstico , Delírio/etiologia , Acidente Vascular Cerebral/complicações , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Delírio/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Escala de Coma de Glasgow , Humanos , Incidência , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Acidente Vascular Cerebral/epidemiologia , Adulto JovemRESUMO
The safety profile of fingolimod is well established in clinical trials and post-marketing studies. This study aimed to evaluate the safety and tolerability of fingolimod in a cohort of Italian patients with relapsing-remitting multiple sclerosis (RRMS). This is a non-comparative, open-label, multicentre, interventional study conducted in patients with RRMS with no suitable alternative treatment option. Safety and tolerability of fingolimod 0.5 mg were assessed by recording adverse events (AEs) and serious AEs (SAEs). Of the 906 patients enrolled in the study, 91 % of the patients completed the study. AEs and SAEs were reported in 35.4 and 2.9 % of the patients, respectively. Most common AEs reported were headache (4.1 %), influenza (2.1 %), lymphopenia (1.8 %), asthenia (1.8 %) and pyrexia (1.8 %). Increased alanine aminotransferase levels and hypertension were reported as AE in 1.0 and 1.4 % of the patients, respectively. Macular oedema was reported in three patients. These results emphasize the safety of fingolimod in patients representing the real-world clinical practice in the Italian population. Fingolimod was safe and well tolerated in this population, which, compared to those enrolled in pivotal trials in terms of concomitant diseases and used medications, is broader. TRIAL REGISTRATION: EudraCT 2011-000770-60.
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Cloridrato de Fingolimode/efeitos adversos , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Feminino , Cloridrato de Fingolimode/uso terapêutico , Cefaleia/induzido quimicamente , Humanos , Imunossupressores/uso terapêutico , Infecções/induzido quimicamente , Itália , Edema Macular/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Our objectives were: (1) to assess amyotrophic lateral sclerosis (ALS) incidence and its trend over time in Liguria, an Italian north-western region, performing an analysis of data prospectively collected from 1 January 2009 to 31 December 2014; (2) to determine the mean and median survival in the 2009-2014 Ligurian ALS incident cases; and (3) to evaluate the presence of disease prognostic factors. The Liguria Register for ALS (LIGALS) is an ongoing, multicentre prospective register enrolling all ALS incident cases in Liguria. Cases were identified using several concurrent sources. ALS diagnosis was based on El Escorial revised criteria (EEC-R). Two hundred and ninety-eight patients were enrolled in this study. The mean annual crude incidence rate in the 2009-2014 period was 3.11/100,000 population (95% CI 2.77-3.49); the point prevalence at 31 December 2014 was 7.85/100,000 (95% CI 6.54-9.36) population. Survival analysis demonstrated a median survival from symptom onset of 37.0 months (95% CI 32.0-42.0). In conclusion, ALS crude incidence in Liguria is higher compared to other Italian regions. Clinical and epidemiological data are comparable with those of the Italian ALS population. Survival analysis showed that higher age at onset, bulbar onset, definite EEC-R diagnostic category and a shorter diagnostic delay are related with worse outcomes.