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OBJECTIVE: Evaluate the effect of subcutaneous interferon ß-1a (sc IFN ß-1a) versus placebo on the evolution of T1-weighted MRI lesions and central brain atrophy in in patients with a first clinical demyelinating event (FCDE). METHODS: Post hoc analysis of baseline-to-24 month MRI data from patients with an FCDE who received sc IFN ß-1a 44 µg once- (qw) or three-times-weekly (tiw), or placebo, in REFLEX. Patients were grouped according to treatment regimen or conversion to clinically definite MS (CDMS) status. The intensity of new lesions on unenhanced T1-weighted images was classified as T1 iso- or hypo-intense (black holes) and percentage ventricular volume change (PVVC) was assessed throughout the study. RESULTS: In patients not converting to CDMS, sc IFN ß-1a tiw or qw, versus placebo, reduced the overall number of new lesions (P < 0.001 and P = 0.005) and new T1 iso-intense lesions (P < 0.001 and P = 0.002) after 24 months; only sc IFN ß-1a tiw was associated with fewer T1 hypo-intense lesions versus placebo (P < 0.001). PVVC findings in patients treated with sc IFN ß-1a suggested pseudo-atrophy that was ~ fivefold greater versus placebo in the first year of treatment (placebo 1.11%; qw 4.28%; tiw 6.76%; P < 001); similar findings were apparent for non-converting patients. CONCLUSIONS: In patients with an FCDE, treatment with sc IFN ß-1a tiw for 24 months reduced the number of new lesions evolving into black holes.
Assuntos
Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente , Humanos , Adjuvantes Imunológicos/efeitos adversos , Atrofia/tratamento farmacológico , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Interferon beta-1a/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/induzido quimicamente , Resultado do TratamentoRESUMO
OBJECTIVES: To assess natural history and 12-month change of a series of scales and functional outcome measures in a cohort of 117 patients with primary mitochondrial myopathy (PMM). METHODS: Twelve months follow-up data of 117 patients with PMM were collected. We analysed the 6-min walk test (6MWT), timed up-and-go test (× 3) (3TUG), five-times sit-to-stand test (5XSST), timed water swallow test (TWST), and test of masticating and swallowing solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional pain inventory as patient-reported outcome measures. PMM patients were divided into three phenotypic categories: mitochondrial myopathy (MiMy) without extraocular muscles involvement, pure chronic progressive external ophthalmoplegia (PEO) and PEO&MiMy. As 6MWT is recognized to have significant test-retest variability, we calculated MCID (minimal clinically important difference) as one third of baseline 6 min walking distance (6MWD) standard deviation. RESULTS: At 12-month follow-up, 3TUG, 5XSST and FSS were stable, while TWST and the perceived pain severity (WHYMPI) worsened. 6MWD significantly increased in the entire cohort, especially in the higher percentiles and in PEO patients, while was substantially stable in the lower percentile (< 408 m) and MiMy patients. This increase in 6MWD was considered not significant, as inferior to MCID (33.3 m). NMDAS total score showed a slight but significant decline at 12 months (0.9 point). The perceived pain severity significantly worsened. Patients with PEO performed better in functional measures than patients with PEO&MiMy or MiMy, and had lower values of NMDAS. CONCLUSIONS: PMM patients showed a slow global decline valued by NMDAS at 12 months; 6MWT was a more reliable measurement below 408 m, substantially stable at 12 months. PEO patients had better motor performance and lower NMDAS than PEO&MiMy and MiMy also at 12 months of follow-up.
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Miopatias Mitocondriais , Oftalmoplegia Externa Progressiva Crônica , Humanos , Seguimentos , Teste de Caminhada/métodos , Miopatias Mitocondriais/complicações , Miopatias Mitocondriais/diagnóstico , Fatores de Tempo , CaminhadaRESUMO
INTRODUCTION: In recent years, different studies have highlighted the importance of B cells in the pathophysiology of multiple sclerosis (MS): they secrete cytokines to modulate the inflammatory environment, present antigens for the activation of T lymphocytes, and they secrete antibodies contributing to the destruction of the myelin sheath. Combined, these findings have lead to new possible means for treating MS. AREAS COVERED: In this review, we provide an up-to-date overview of the characteristics of ofatumumab (aka Kesimpta), and the differences between this drug and the other anti-CD20 monoclonal antibodies used to treat MS. EXPERT OPINION: The evolution of disease-modifying treatment algorithms in MS underlines the importance of starting treatment as soon as the diagnosis is defined, and with adequate 'treatment intensity.' Monoclonal antibodies and other aggressive treatments are now considered as an option at the clinical presentation of the disease, based to the prognostic profile emerging through clinical and paraclinical investigations. The recent adoption of new diagnostic criteria allows for the early diagnosis of MS. This, together with the availability of disease-modifying therapies (DMTs), such as ofatumumab, with a good efficacy/safety profile and which are easy to administer, could contribute to significant improvements in the long-term prognosis of MS.
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Esclerose Múltipla , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Injeções Subcutâneas , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/tratamento farmacológicoRESUMO
BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system. It is a complex and heterogeneous disease caused by a combination of genetic and environmental factors, and it can cluster in families. OBJECTIVE: to evaluate at gene-level the aggregate contribution of predicted damaging low-frequency and rare variants to MS risk in multiplex families. METHODS: We performed whole exome sequencing (WES) in 28 multiplex MS families with at least 3 MS cases (81 affected and 42 unaffected relatives) and 38 unrelated healthy controls. A gene-based burden test was then performed, focusing on two sets of candidate genes: i) literature-driven selection and ii) data-driven selection. RESULTS: We identified 11 genes enriched with predicted damaging low-frequency and rare variants in MS compared to healthy individuals. Among them, UBR2 and DST were the two genes with the strongest enrichment (p = 5 × 10-4 and 3 × 10-4, respectively); interestingly enough the association signal in UBR2 is driven by rs62414610, which was present in 25% of analysed families. CONCLUSION: Despite limitations, this is one of the first studies evaluating the aggregate contribution of predicted damaging low-frequency and rare variants in MS families using WES data. A replication effort in independent cohorts is warranted to validate our findings and to evaluate the role of identified genes in MS pathogenesis.
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Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Ubiquitina-Proteína Ligases/genética , Estudos de Coortes , Variação Genética , Humanos , Itália , Mutação de Sentido Incorreto , Sequenciamento do ExomaRESUMO
Fingolimod (FTY), a second-line oral drug approved for relapsing remitting Multiple Sclerosis (RRMS) acts in preventing lymphocyte migration outside lymph nodes; moreover, several lines of evidence suggest that it also inhibits myeloid cell activation. In this study, we investigated the transcriptional changes induced by FTY in monocytes in order to better elucidate its mechanism of action. CD14+ monocytes were collected from 24 RRMS patients sampled at baseline and after 6 months of treatment and RNA profiles were obtained through next-generation sequencing. We conducted pathway and sub-paths analysis, followed by centrality analysis of cell-specific interactomes on differentially expressed genes (DEGs). We investigated also the predictive role of baseline monocyte transcription profile in influencing the response to FTY therapy. We observed a marked down-regulation effect (60 down-regulated vs. 0 up-regulated genes). Most of the down-regulated DEGs resulted related with monocyte activation and migration like IL7R, CCR7 and the Wnt signaling mediators LEF1 and TCF7. The involvement of Wnt signaling was also confirmed by subpaths analyses. Furthermore, pathway and network analyses showed an involvement of processes related to immune function and cell migration. Baseline transcriptional profile of the HLA class II gene HLA-DQA1 and HLA-DPA1 were associated with evidence of disease activity after 2 years of treatment. Our data support the evidence that FTY induces major transcriptional changes in monocytes, mainly regarding genes involved in cell trafficking and immune cell activation. The baseline transcriptional levels of genes associated with antigen presenting function were associated with disease activity after 2 years of FTY treatment.
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Cloridrato de Fingolimode/uso terapêutico , Perfilação da Expressão Gênica/métodos , Leucócitos Mononucleares/efeitos dos fármacos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/genética , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Adulto , Células Cultivadas , Feminino , Cloridrato de Fingolimode/farmacologia , Seguimentos , Humanos , Leucócitos Mononucleares/fisiologia , Receptores de Lipopolissacarídeos/imunologia , Masculino , Esclerose Múltipla Recidivante-Remitente/imunologia , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacologia , Transcriptoma/efeitos dos fármacos , Transcriptoma/fisiologia , Resultado do Tratamento , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologiaRESUMO
With more widespread prolonged survival, Duchenne muscular dystrophy patients progressively experience multisystem complications. We retrospectively reviewed the charts of 132 Duchenne patients (112 alive/20 dead, age 3.5÷32.3 years) with the aims: 1) to provide a comprehensive description of the clinical status considering different aspects of the disease; 2) to propose a new scoring tool able to consider and pool together heterogeneous different functional. Five functions were analyzed: cardiac, respiratory, nutritional, ambulation and scoliosis. For each function, different items were considered and classified according to clinical severity (as indicated by international guidelines) and an incremental scoring was assigned. In addition, a global score incorporating all functions was defined. The scoring system confirmed that despite the significant protective role of steroids, all functions deteriorated with age. The severity of the global score became significantly higher since the age of 13 years. The severity of cardiac, respiratory and nutritional dysfunction was higher since 18 years. Deceased patients were characterized by significantly worse cardiac function, absence of steroid therapy and later use of respiratory assistive devices. The index proposed in this pilot study is a promising tool able to aggregate and correlate heterogeneous functions. It could become either an individual prognostic indicator of decline or a global score to evaluate changes in clinical trials therefore allowing multicenter studies, optimizing the management of both the primary and the secondary complications of the disease and understanding their relative impact.
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Distrofia Muscular de Duchenne/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Itália , Masculino , Projetos Piloto , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto JovemRESUMO
BACKGROUND: Long-term safety data are of particular interest for any newly approved treatment in multiple sclerosis such as cladribine tablets 10 mg (MAVENCLAD®; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg), which is approved in Europe and the USA. Here we provide the final report on the integrated analysis of the safety profile of cladribine tablets 3.5 mg/kg from the clinical development program, including final data from the PREMIERE registry. METHODS: Safety data for cladribine tablets 3.5 mg/kg from three previously reported Phase III studies (CLARITY, CLARITY Extension and ORACLE-MS), as well as the prospective, observational PREMIERE registry (which ran from November 2009 to October 2018; consisting of patients who had participated in at least one of the Phase III trials) were combined to provide the Monotherapy Oral cohort. Serious adverse events (SAEs) and predefined SAEs of special interest were recorded. Observation-adjusted incidence rates per 100 patient-years (Adj-AE per 100 PY) were used to assess adverse events (AEs). Standardized incidence ratios for malignancies were calculated in relation to a matched GLOBOCAN reference population, and risk differences (cladribine tablets versus placebo) were estimated. RESULTS: The Monotherapy Oral cohort comprised 923 patients who received cladribine tablets 3.5 mg/kg and 641 patients who received placebo. Overall, the reported number of SAEs was higher in the cladribine tablets 3.5 mg/kg group (133/923 [14.4%] patients with at least 1 SAE), versus the placebo group (68/641 [10.6%] patients with at least 1 SAE). Four patients in the cladribine tablets 3.5 mg/kg group had lymphopenia classified as a serious event (resulting in an Adj-AE of 0.10 per 100 PY) and 2 patients had serious herpes zoster (resulting in an Adj-AE of 0.05 per 100 PY). There were no cases in the corresponding placebo groups. There was no difference between the cladribine tablets 3.5 mg/kg group and placebo in the overall incidence of infections. However herpetic infection AEs occurred more frequently in the cladribine tablets 3.5 mg/kg group (driven primarily by herpes zoster, followed by oral herpes and herpes simplex). Overall, there was a numerical imbalance in malignancy incidence between cladribine tablets 3.5 mg/kg and placebo, with an Adj-AE of 0.26 and 0.12 per 100 PY, respectively; however the difference was not statistically significant. The rate of malignancies observed with cladribine tablets 3.5 mg/kg in the final integrated safety analysis was not different from the expected rate in the matched GLOBOCAN reference population (standardized incidence ratio, 0.88; 95% CI, 0.44-1.69). CONCLUSION: Additional patient-years of observation do not significantly alter the conclusions of earlier interim analyses, and no new major safety findings were identified in this consolidated analysis of safety data of cladribine tablets 3.5 mg/kg monotherapy in patients with relapsing-remitting multiple sclerosis.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Cladribina/efeitos adversos , Europa (Continente) , Humanos , Imunossupressores/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Estudos Prospectivos , ComprimidosRESUMO
Immune-related adverse events (irAE) during the administration of immune-checkpoint inhibitors (ICIs) become more evident due to the increased use of these therapies. To remind the importance of early recognition of this phenomenon, we report a paradigmatic case characterized by severe systemic inflammatory myopathy and severe cardiac involvement that abruptly precipitated in an untoward ending after one single dose of Pembrolizumab.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Miosite/tratamento farmacológico , Miotoxicidade/etiologia , Evolução Fatal , HumanosAssuntos
Alemtuzumab/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/complicações , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Masculino , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Resultado do TratamentoRESUMO
In amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), spinal and lower brainstem motor neurons degenerate, but some motor neuron subtypes are spared, including oculomotor neurons (OMNs). The mechanisms responsible for this selective degeneration are largely unknown, but the molecular signatures of resistant and vulnerable motor neurons are distinct and offer clues to neuronal resilience and susceptibility. Here, we demonstrate that healthy OMNs preferentially express Synaptotagmin 13 (SYT13) compared to spinal motor neurons. In end-stage ALS patients, SYT13 is enriched in both OMNs and the remaining relatively resilient spinal motor neurons compared to controls. Overexpression of SYT13 in ALS and SMA patient motor neurons in vitro improves their survival and increases axon lengths. Gene therapy with Syt13 prolongs the lifespan of ALS mice by 14% and SMA mice by 50% by preserving motor neurons and delaying muscle denervation. SYT13 decreases endoplasmic reticulum stress and apoptosis of motor neurons, both in vitro and in vivo. Thus, SYT13 is a resilience factor that can protect motor neurons and a candidate therapeutic target across motor neuron diseases.
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Esclerose Lateral Amiotrófica/metabolismo , Doença dos Neurônios Motores/patologia , Neurônios Motores/metabolismo , Sinaptotagminas/metabolismo , Esclerose Lateral Amiotrófica/genética , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Doença dos Neurônios Motores/metabolismo , Superóxido Dismutase/genéticaRESUMO
OBJECTIVE: To assess the usefulness of upper limb (UE) motor evoked potential (MEPs) as a marker of motor impairment in a cohort of people with progressive multiple sclerosis (PwPMS). METHODS: we evaluated UE and lower extremities (LE) MEPs, 6-minutes walk-test (6MWT), 10-meter walk-test (10MWT), EDSS, 9-hole peg-test (9HPT), and measures of strength (MRC) and tone (MAS) to the UE and LE in 50 PwPMS (EDSS 4.0-6.5; P ≥ 3, C ≤ 2). RESULTS: Bilateral absence of LE-MEPs, found in 74% of cases, was associated with worse 10MWT and 6MWT. UE-MEPs were rarely absent (8%) but often delayed (74%). Abnormal UE-MEPs were associated with worse performance at 9HPT (25.8 vs 33.2 s). UE-MEPs latency correlated with 10MWT (rho = 0.597), 6MWT (rho = -0.425) and EDSS (rho = 0.296). CONCLUSION: UE-MEPs may represent a clinically relevant outcome measure to quantify corticospinal tract integrity in PwPMS, at least when LE-MEPs cannot provide a measurable response. SIGNIFICANCE: The strive for novel remyelination strategies in MS points to the need for quantitative conduction measurements in addition to clinical outcomes. The frequent absence of MEPs to the lower limbs in PwPMS may greatly limits their usefulness in monitoring progression or response to therapies. With this respect, the upper extremities may represent a better target.
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Eletromiografia/métodos , Potencial Evocado Motor , Esclerose Múltipla/diagnóstico , Adulto , Braço/fisiopatologia , Eletromiografia/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/terapia , Tempo de Reação , Resultado do TratamentoRESUMO
BACKGROUND: Spasticity is a frequent multifactorial manifestation of multiple sclerosis (MS), affecting mostly the chronic courses of the disease. Its impact on patient functioning and quality of life is profound. Treatment of spasticity includes oral and intrathecal anti-spastic drugs, muscle injections with relaxant agents, physical therapy, electrical and magnetic stimulation and peripheral nerve stimulation, alone or in various combinations. METHODS: This Italian consensus on the treatment of spasticity in MS was produced by a large group of Italian MS experts in collaboration with neurophysiologists, experts in the production of guidelines and patients' representatives operating under the umbrella of the Italian Neurological Society, the Associazione Italiana Sclerosi Multipla and the European Charcot Foundation. This guideline was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 11 questions were formulated following the PICO framework (patients, intervention, comparator, outcome). Controlled studies only were included in the analysis. RESULTS: Despite some consistent limitations due to the poor methodological quality of most studies, there was a consensus on a strong recommendation for the use of intrathecal baclofen, oromucosal spray of nabiximols and intramuscular injection of botulinum toxin. The level of recommendation was weak for oral baclofen, tizanidine, gabapentin, benzodiazepines and transcranial magnetic stimulation. CONCLUSIONS: There is a clear need for new larger multicentre well-designed clinical trials with a duration that allows the persistence of the effects and the long-term safety of the interventions to be evaluated.
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Esclerose Múltipla/complicações , Espasticidade Muscular/terapia , Qualidade de Vida , Estimulação Elétrica Nervosa Transcutânea , Baclofeno/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Clonidina/análogos & derivados , Clonidina/uso terapêutico , Consenso , Gerenciamento Clínico , Gabapentina/uso terapêutico , Humanos , Injeções Intramusculares , Itália , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/terapia , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologiaAssuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Calcinose/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/patologia , Calcinose/complicações , Calcinose/patologia , Humanos , Infarto da Artéria Cerebral Média/etiologia , Infarto da Artéria Cerebral Média/patologia , Masculino , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND AND PURPOSE: The aim was to assess the value of insoluble PABPN1 muscle fibre nuclei accumulation in the diagnosis of atypical cases of oculopharyngeal muscular dystrophy (OPMD). METHODS: Muscle biopsies from a selected cohort of 423 adult patients from several Italian neuromuscular centres were analysed by immunofluorescence: 30 muscle biopsies of genetically proven OPMD, 30 biopsies from patients not affected by neuromuscular disorders, 220 from genetically undiagnosed patients presenting ptosis or swallowing disturbances, progressive lower proximal weakness and/or isolated rimmed vacuoles at muscle biopsy and 143 muscle biopsies of patients affected by other neuromuscular diseases. RESULTS: The detection of insoluble nuclear PABPN1 accumulation is rapid, sensitive (100%) and specific (96%). The revision of our cohort allowed us to discover 23 new OPMD cases out of 220 patients affected with nonspecific muscle diseases. CONCLUSIONS: Oculopharyngeal muscular dystrophy is often misdiagnosed leading to diagnosis delay, causing waste of time and resources. A great number of these cases present symptoms and histological findings frequently overlapping with other muscle diseases, i.e. inclusion body myositis and progressive external ophthalmoplegia. PABPN1 nuclear accumulation is a reliable method for diagnostic purposes and it is safe and useful in helping pathologists and clinicians to direct genetic analysis in the case of suspected OPMD, even when clinical and histological clues are deceptive.
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Núcleo Celular/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular Oculofaríngea/diagnóstico , Proteína I de Ligação a Poli(A)/metabolismo , Núcleo Celular/patologia , Imunofluorescência , Humanos , Músculo Esquelético/patologia , Distrofia Muscular Oculofaríngea/metabolismo , Distrofia Muscular Oculofaríngea/patologiaRESUMO
AIMS: This work aimed to evaluate the antimicrobial activity of pure (ZnO) and doped (ZnMgO) zinc oxide (ZnO) nanoparticles on bacterial pathogens and Saccharomyces cerevisiae to confirm their applicability as an alternative to antibiotics and to estimate their biocompatibility. METHODS AND RESULTS: Microbial growth inhibition on agar plates, microbial viability and adaptation tests in broth with ZnO nanoparticles, spore germination, random amplified polymorphic DNA and SDS-PAGE analysis were conducted to evaluate the effects of ZnO nanoparticles on cell morphology, viability, DNA damage and protein production. For this purpose, Escherichia coli, Salmonella, Listeria monocytogenes, Staphylococcus aureus, Bacillus subtilis and S. cerevisiae were studied after the addition of ZnO nanoparticles to the growth media. The contact with ZnO nanoparticles produced changes in morphology, shape, viability, DNA arrangement (DNA fingerprints) and protein content (SDS-PAGE) in treated cells. CONCLUSIONS: As reported in this study, ZnO nanoparticles have an antimicrobial effect on both prokaryotic and eukaryotic cells. Before using ZnO nanoparticles as antimicrobial agents, it is important to evaluate the target because their effect depends on their composition, size and dose. SIGNIFICANCE AND IMPACT OF THE STUDY: We believe that the results obtained can help to optimize manufactured metal oxide nanoparticles in terms of their composition, size and working concentration. The parameters obtained directly define the applicability and biocompatibility of ZnO nanoparticles and thus are essential for any utilization in food, medicine and industry where pathogen control is crucial.
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Anti-Infecciosos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Nanopartículas/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Óxido de Zinco/farmacologia , Anti-Infecciosos/química , Bacillus subtilis/crescimento & desenvolvimento , Escherichia coli/crescimento & desenvolvimento , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Nanopartículas/química , Saccharomyces cerevisiae/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Óxido de Zinco/químicaRESUMO
OBJECTIVE: To study depression, anxiety, suicide risk, and emotional health-related quality of life (HRQoL) in people with clinically isolated syndrome (CIS) and in early phase multiple sclerosis (MS). METHODS: A systematic literature review was conducted with inclusion criteria of observational studies on outcomes of depression, anxiety, suicide risk, and emotional HRQoL in CIS and within five years since diagnosis of MS. Studies were screened using the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, and study quality was determined for included studies. Meta-analysis and meta-regression were performed if applicable. RESULTS: Fifty-one studies were included in the systematic review. In early phase MS, meta-analyses of the Hospital Anxiety Depression Scale (HADS) indicated prevalence levels of 17% (95% confidence interval (CI): 9 to 25%; pâ¯<â¯.001) for depressive and 35% (95% CI: 28 to 41%; pâ¯<â¯.001) for anxiety symptoms. Meta-regression analyses revealed an increase in mean HADS-D and HADS-A associated with larger sample size, and higher HADS-D mean with increased study quality. Similar depressive and anxiety symptoms were observed in CIS, and increased suicide risk and low emotional HRQoL was associated with depressive symptoms in early phase MS. The methodological quality of the studies was considered fair. CONCLUSIONS: Findings suggest that mild-to-moderate symptoms of depression and anxiety might be prevalent in CIS and in early phase MS. Future research on both clinical populations are needed, especially longitudinal monitoring of emotional outcomes.
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Emoções , Esclerose Múltipla/psicologia , Humanos , Qualidade de Vida , Suicídio/psicologiaRESUMO
BACKGROUND AND PURPOSE: This study aimed to assess the predictive value of multimodal brain magnetic resonance imaging (MRI) on survival in a large cohort of patients with motor neuron disease (MND), in combination with clinical and cognitive features. METHODS: Two hundred MND patients were followed up prospectively for a median of 4.13 years. At baseline, subjects underwent neurological examination, cognitive assessment and brain MRI. Grey matter volumes of cortical and subcortical structures and diffusion tensor MRI metrics of white matter tracts were obtained. A multivariable Royston-Parmar survival model was created using clinical and cognitive variables. The increase of survival prediction accuracy provided by MRI variables was assessed. RESULTS: The multivariable clinical model included predominant upper or lower motor neuron presentations and diagnostic delay as significant prognostic predictors, reaching an area under the receiver operating characteristic curve (AUC) of a 4-year survival prediction of 0.79. The combined clinical and MRI model including selected grey matter fronto-temporal volumes and diffusion tensor MRI metrics of the corticospinal and extra-motor tracts reached an AUC of 0.89. Considering amyotrophic lateral sclerosis patients only, the clinical model including diagnostic delay and semantic fluency scores provided an AUC of 0.62, whereas the combined clinical and MRI model reached an AUC of 0.77. CONCLUSION: Our study demonstrated that brain MRI measures of motor and extra-motor structural damage, when combined with clinical and cognitive features, are useful predictors of survival in patients with MND, particularly when a diagnosis of amyotrophic lateral sclerosis is made.
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Imagem de Tensor de Difusão , Substância Cinzenta/diagnóstico por imagem , Doença dos Neurônios Motores/diagnóstico por imagem , Doença dos Neurônios Motores/mortalidade , Doença dos Neurônios Motores/fisiopatologia , Idoso , Diagnóstico Tardio , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos TeóricosAssuntos
Arteriosclerose Intracraniana/complicações , Trombose Intracraniana/complicações , Acidente Vascular Cerebral/etiologia , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/diagnóstico por imagem , Masculino , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
Alemtuzumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS). During the immune reconstitution following the use of this treatment severe secondary autoimmune diseases (SADs) can develop. We present the case of a patient affected by active MS who failed to achieve disease control with several disease-modifying drugs and was thereafter successfully treated with alemtuzumab, obtaining no evidence of disease activity and a high quality of life. Twenty months after the first infusion of alemtuzumab the patient developed acquired haemophilia A (AHA), a treatable but potentially lifethreatening condition that should be considered a possible SADs associated to this drug. In order to allow an early diagnosis and to prevent possible complications of AHA, routine coagulation tests (prothrombin time and activated partial thromboplastin time) should be included in the laboratory serological monitoring of patients treated with alemtuzumab.
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Alemtuzumab/efeitos adversos , Hemofilia A/induzido quimicamente , Imunossupressores/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Adulto , Doenças Autoimunes/induzido quimicamente , Feminino , Humanos , Esclerose Múltipla/complicações , Resultado do TratamentoRESUMO
The coexistence of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in the same family is a rare event. We report a familial case originating from Sardinia of two siblings: one with NMOSD and one with MS. Human leukocyte antigen (HLA) typing showed that the two affected siblings were HLA-identical, sharing risk-increasing alleles, while a younger unaffected sister was haploidentical to her siblings but she also carried protective alleles. Our findings confirm the role of HLA in raising the risk to develop CNS inflammatory diseases and provide further knowledge on the relationship between NMOSD and MS.