RESUMO
OBJECTIVE: To validate sphingomyelin (SM) dosage in the cerebrospinal fluid (CSF) of patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) as a reliably assessable biomarker. METHODS: We prospectively enrolled 184 patients from six Italian referral centres, in whom CSF SM levels were quantified by a fluorescence-based assay optimised and patented in our laboratory. RESULTS: We confirmed increased levels of SM in the CSF of patients affected by typical CIDP (n=35), atypical CIDP (n=18) and acute inflammatory demyelinating polyradiculoneuropathy, AIDP (n=12) compared with patients affected by non-demyelinating neurological diseases, used as controls (n=85) (p<0.0001, p=0.0065 and p<0.0001, respectively). In patients with CIDP classified for disease stage, SM was higher in active CIDP compared with both controls and stable CIDP (p<0.0001), applying for a selective tool to treatment tailoring or withdrawal. SM was also increased in AIDP compared with axonal GBS, discerning the demyelinating from axonal variant of the disease. SM did not correlate with CSF protein levels, stratifying patients independently from commonly used CSF indexes, and displaying high specificity to avoid potential misdiagnosis. Finally, SM correlated with the main clinical scores and some neurophysiological parameters in patients with CIDP and AIDP. CONCLUSIONS: CSF SM is a diagnostic and staging wet biomarker for acquired demyelinating neuropathies and may effectively improve the management of patients affected by GBS and CIDP.
Assuntos
Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/líquido cefalorraquidiano , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Esfingomielinas/líquido cefalorraquidiano , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROCRESUMO
The management of multiple sclerosis patients with persistent disease activity under alemtuzumab treatment is not established yet. Concerns have been raised on the safety of autologous haematopoietic stem cell transplantation (aHSCT) after alemtuzumab treatment because of the risk of serious infectious adverse events. We report short-term safety and efficacy data from three patients treated with aHSCT following alemtuzumab treatment. Early adverse events were consistent with expected transplant toxicities. All patients were free of disease activity at the last follow-up. Our data suggest that aHSCT can be considered as a rescue treatment strategy for MS patients with persistent disease activity during alemtuzumab treatment.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Esclerose Múltipla , Alemtuzumab , Humanos , Esclerose Múltipla/tratamento farmacológico , Transplante AutólogoRESUMO
Vanishing White Matter Disease (VWMD) is a rare autosomal recessive leukoencephalopathy . The classical presentation is characterized by a severe cerebellar ataxia, spasticity, neurological deterioration with a chronic progressive course and episodes of acute neurological deterioration after stress conditions.We report a 52-year-old man with VWMD and atypical features who manifested two major events of transient aphasia eleven years apart with complete recovery in 48 hours. No cognitive decline was present. Brain MRI revealed typical aspects of VWMD including diffuse leukoencephalopathy with relative sparing of U-fibers. We identified the presence of c.592G>A (p.Glu198Lys) and c.1360 C>T (p.Pro454Ser) mutations in EIF2B5.
Assuntos
Leucoencefalopatias , Substância Branca , Adulto , Fator de Iniciação 2B em Eucariotos/genética , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Substância Branca/diagnóstico por imagemRESUMO
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 numéricosRESUMO
Isolated cognitive relapses (ICRs) are transient deficits in cognitive performance that are the only presentation of a multiple sclerosis (MS) relapse. Here, we evaluated the impact of ICRs on cognitive difficulties in daily activities (assessed with the Multiple Sclerosis Neuropsychological Screening Questionnaire, Informant Version (MSNQ-I)) to characterize ICRs' clinical relevance. We used 2-year-long retrospective data to compare 15 relapsing-remitting MS (RRMS) patients with ICRs with 57 RRMS patients presenting an asymptomatic gadolinium enhancing lesion (and no-ICRs). ICRs were associated not only with neuropsychological performance decline but also with an increase in the daily cognitive difficulties. These findings support the ecological relevance of ICRs.
Assuntos
Disfunção Cognitiva , Esclerose Múltipla Recidivante-Remitente , Qualidade de Vida , Adulto , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Recidiva , Estudos RetrospectivosRESUMO
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.
Assuntos
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
This document presents the guidelines for the cerebrospinal fluid (CSF) analysis and the determination of oligoclonal bands (OCBs) as pivotal tests in neuroinflammatory pathologies of the central nervous system. The guidelines have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on the pathologies in which the CSF analysis is indicated, and, particularly, on those characterized by the presence of OCBs in the intrathecal compartment, indications and limits of CSF analysis and OCB determination, instructions for result interpretation, and agreed laboratory protocols (Appendix) are reported for the communicative community of neurologists and clinical pathologists.
Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Bandas Oligoclonais/líquido cefalorraquidiano , Humanos , Bandas Oligoclonais/análiseRESUMO
BACKGROUND: Autologous hematopoietic stem cell transplantation (AHSCT) has been successfully used to treat aggressive forms of multiple sclerosis (MS) that are unresponsive to approved therapies. In the last years, in view of the risk of mortality related to the procedure, the utilization of low-intensity conditioning regimens has been considered. OBJECTIVE: To report magnetic resonance imaging (MRI) and clinical data in a small cohort of patients treated with a low-intensity lympho-ablative regimen, followed by AHSCT. METHODS: Seven patients affected by relapsing-remitting MS (RRMS) underwent AHSCT, with cyclophosphamide 120 mg/kg in 2 days as the conditioning regimen; and were then followed with serial MRI evaluations until 36 months, with clinical evaluations until 60 months. RESULTS: The mean number of gadolinium (Gd)-enhancing lesions significantly decreased after treatment, but a complete suppression of inflammatory activity was not obtained. No deaths occurred, but every patient developed adverse events, although not severe. After 5 years of follow-up, two patients remained stable, one patient markedly improved and four patients had a mild progression of the disease. Only one patient experienced a relapse after treatment. CONCLUSION: A low-intensity conditioning regimen with AHSCT has a profound effect on MRI inflammation and relapses, but is not able to completely abrogate MRI activity and disease progression of aggressive RRMS.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Ciclofosfamida/administração & dosagem , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Optimal patient selection would improve the risk-benefit ratio of natalizumab treatment for relapsing-remitting multiple sclerosis (RR MS). Clinical features of subjects responding to natalizumab have not been univocally recognized. METHODS: Longitudinal data on RR MS patients treated with natalizumab in Liguria, Italy are reported. Predictors of relapse occurrence and disability improvement were analyzed with a logistic regression method in subjects treated for one year (N = 62). A new score, called "Better EDSS Trend (BET)", was devised to describe the impact of the treatment on disability. Changes in annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) after one and two years and proportion of disease-free patients were evaluated. RESULTS: Previous EDSS worsening plus ARR ≥ 2 increased the risk of relapse during the treatment [Odds Ratio (OR) 4.12, P = 0.04], but this was not associated with an increase in disability at one year. EDSS 3.0-3.5 or high disease activity were associated with neurological improvement in the first year of treatment (respectively OR 5.78, P = 0.05 and OR 4.80, P = 0.05). Positive BET score, i.e. improvement in the disability trend, was observed in 40.3% of patients, and correlated with high ARR in the year before treatment (OR 1.69, P = 0.03). CONCLUSION: Subjects with EDSS 3.0-3.5 and those with very active disease in the year before treatment are most likely to improve in neurological function under natalizumab. A relapse in the first year of treatment is associated to high pre-treatment disease activity; however, since the occurrence of a relapse did not have a negative impact on clinical improvement at one year, we suggest that it should not lead to treatment discontinuation. We propose BET as an additional endpoint of treatment response in MS.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Imunossupressores/efeitos adversos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Natalizumab , Seleção de Pacientes , Valor Preditivo dos Testes , Recidiva , Projetos de Pesquisa , Adulto JovemRESUMO
Multiple sclerosis (MS) is a complex disease triggered by environmental and genetic agents, and clinically characterized by bout onset (BOMS) or progressive onset (PrMS). We collected clinical and familial aggregation data in a cohort of 518 Italian PrMS patients, and compared with 400 BOMS cases. An increased prevalence of MS in first-degree relatives of Italian PrMS was found. Familial aggregation is not influenced by probands' clinical course, and there is no disease course concordance within MS families. These data are useful in counseling MS patients affected with different clinical courses of the disease.
Assuntos
Família , Predisposição Genética para Doença , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/fisiopatologia , Fenótipo , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Progressão da Doença , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
Interferon beta (IFNß) was the first specific disease-modifying treatment licensed for relapsing-remitting multiple sclerosis, and is still one of the most commonly prescribed treatments. A strong body of evidence supports the effectiveness of IFNß preparations in reducing the annual relapse rate, magnetic resonance (MRI) disease activity and disease progression. However, the development of binding/neutralizing antibodies (BAbs/NAbs) during treatment negatively affects clinical and MRI outcomes. Therefore, guidelines for the clinical use for the detection of NAbs in MS may result in better treatment of these patients. In October 2012, a panel of Italian neurologists from 17 MS clinics convened in Milan to review and discuss data on NAbs and their clinical relevance in the treatment of MS. In this paper, we report the panel's recommendations for the use of IFNß Nabs detection in the early identification of IFNß non-responsiveness and the management of patients on IFNß treatment in Italy, according to a model of therapeutically appropriate care.
Assuntos
Anticorpos Neutralizantes/sangue , Fatores Imunológicos/uso terapêutico , Interferon beta/imunologia , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Diagnóstico Precoce , Humanos , Fatores Imunológicos/imunologia , Itália , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/economia , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/economia , Esclerose Múltipla Recidivante-Remitente/imunologia , Proteínas de Resistência a Myxovirus/metabolismo , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We studied the detection of Treponema pallidum (TP)-IgM antibodies in the serum of 69 patients treated for syphilis. The persistence of TP-IgM antibodies in serum for more than 3 years was the only clue to suspect an active infection and, therefore, to investigate a central nervous system involvement.
Assuntos
Anticorpos Antibacterianos , Imunoglobulina M , Sífilis , Treponema pallidum , Humanos , Treponema pallidum/imunologia , Imunoglobulina M/sangue , Anticorpos Antibacterianos/sangue , Sífilis/sangue , Sífilis/imunologia , Sífilis/diagnóstico , Sífilis/microbiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Fatores de TempoRESUMO
BACKGROUND: Fatigue is a common symptom in individuals with multiple sclerosis (MS). To date, the pathophysiology of fatigue in MS remains ill-understood; however, converging evidence seems to suggest that a key factor in fatigue development might be the dysregulation of neuropsychological processes underpinning the evaluation of the rewarding outcomes of actions. OBJECTIVES: To explore the relationship between reward-related cognition and fatigue in MS and to explore the usefulness of reward perception testing to predict the efficacy of monoamine-modulating drugs on fatigue. METHODS: The study included 104 fatigued and 70 fatigue-free Relapsing-Remitting MS patients. All subjects were screened for the lack of any significant mood, cognitive, or personality disorders that could confound results. The different facets of the motivation system such as the patient's reward perception were assessed at baseline using the Behavioural Inhibition and Behavioural Activation Scales (BIS/BAS). Fatigue was assessed with the Modified Fatigue Impact Scale (MFIS). Fatigue values after three months of therapy with escitalopram or bupropion were correlated with those baseline BIS/BAS scores. RESULTS: Fatigued patients demonstrated lower reward responsiveness compared to fatigue-free subjects. Reward responsiveness scores were found to be associated with baseline MFIS scores and with fatigue reduction after treatment with bupropion: Lower reward responsiveness at baseline predicted higher fatigue remission rates in bupropion-treated patients, as compared with escitalopram-treated patients. DISCUSSION: Reward responsiveness was linked with MS-related fatigue and might represent one of its key cognitive underpinnings. Our results suggest that evaluation of reward responsiveness could provide useful information to guide individualized therapy of MS-related fatigue.
Assuntos
Cognição/fisiologia , Fadiga/psicologia , Esclerose Múltipla/fisiopatologia , Esclerose Múltipla/psicologia , Recompensa , Adulto , Ansiedade/psicologia , Atenção/fisiologia , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Citalopram/efeitos adversos , Citalopram/uso terapêutico , Depressão/psicologia , Avaliação da Deficiência , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Distúrbios do Sono por Sonolência Excessiva/etiologia , Inibidores da Captação de Dopamina/efeitos adversos , Inibidores da Captação de Dopamina/uso terapêutico , Fadiga/tratamento farmacológico , Fadiga/etiologia , Feminino , Humanos , Inibição Psicológica , Masculino , Esclerose Múltipla/tratamento farmacológico , Testes Neuropsicológicos , Percepção/fisiologia , Personalidade , Tempo de Reação/fisiologia , Recidiva , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Treatment with fingolimod for multiple sclerosis (MS) reduces the efficacy of COVID-19 vaccination. The aim of this exploratory study was to evaluate whether main lymphocyte subsets and demographic features correlated to the subsequent increase in anti-SARS-CoV2 antibodies following the third dose of COVID-19 vaccination in fingolimod-treated MS patients. METHODS: This was a prospective single-center observational exploratory study including a subgroup of adult patients with MS (pwMS) in treatment with fingolimod who underwent COVID-19 vaccination. The association of anti-SARS-CoV2 antibody levels (reported as the Log10 of the difference between the post and pre third dose levels) with the total number and percentage of CD3+ T and CD19+ B was assessed by a linear regression model adjusted for age and sex. RESULTS: We found that peripheral blood CD19+ B lymphocytes before the third dose of vaccination in pwMS treated with fingolimod predict the subsequent increase of anti-SARS-CoV2 antibodies. CONCLUSION: This work suggests that evaluating the percentage of CD19+ B cells may be important to identify patients at risk of not producing SARS-CoV-2 antibodies, with possible reduced protection from COVID-19.
Assuntos
Linfócitos B , Vacinas contra COVID-19 , COVID-19 , Cloridrato de Fingolimode , Esclerose Múltipla , Adulto , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Anticorpos Antivirais , Linfócitos B/imunologia , COVID-19/complicações , COVID-19/prevenção & controle , COVID-19/terapia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/uso terapêutico , Cloridrato de Fingolimode/administração & dosagem , Cloridrato de Fingolimode/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2 , VacinaçãoRESUMO
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder. Since acetylcholine (ACh) is known to participate in the inflammatory response, we investigated the possible relationship between pro-inflammatory cytokines and acetylcholine levels in relapsing-remitting multiple sclerosis (RR-MS) patients. Levels of ACh and pro-inflammatory cytokines IL1-β and IL-17 were measured both in cerebrospinal fluid (CSF) and sera of 22 RR-MS patients in the relapsing phase and in 17 control subjects affected by other non-neurological diseases (OND). We observed higher levels of pro-inflammatory cytokines such as IL-1β and IL-17 in both CSF and serum of RR-MS patients compared to control subjects. Moreover, ACh levels were lower in CSF and serum of RR-MS patients compared to levels of control subjects. Although the relationship between high inflammatory cytokine levels and low ACh levels need to be further investigated in the future, our data suggest that IL-1β, and cytokines induced by it, such as IL-17 and ACh, may be involved in the pathogenesis of MS.
Assuntos
Acetilcolina/análise , Interleucina-17/análise , Interleucina-1/análise , Acetilcolina/sangue , Acetilcolina/líquido cefalorraquidiano , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-1/sangue , Interleucina-1/líquido cefalorraquidiano , Interleucina-17/sangue , Interleucina-17/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Adulto JovemRESUMO
BACKGROUND: Progranulin (PGRN) is a fundamental neurotrophic factor, and is also involved in inflammation and wound repair. PGRN may have pro- or anti-inflammatory properties, depending upon proteolysis of the anti-inflammatory parent PGRN protein and the generation of pro-inflammatory granulin peptides. OBJECTIVES: Our objectives were as follows: (1) to evaluate the presence and distribution of PGRN in multiple sclerosis (MS) brain tissue, correlating it with demyelination and inflammation; (2) to evaluate cerebrospinal fluid (CSF) PGRN concentrations in patients with MS and controls, in relationship to the clinical features of the disease. METHODS: Our study involved the following: (1) neuropathological study of PGRN on post-mortem tissue of 19 MS and six control brains; (2) evaluation of PGRN CSF concentration in 40 MS patients, 15 non-inflammatory controls and five inflammatory controls (viral encephalitis). RESULTS: In active demyelinating lesions, PGRN was expressed on macrophages/microglia. In the normal-appearing white matter (NAWM), expression of PGRN was observed on activated microglia. PGRN was expressed by neurons and microglia in cortical lesions and in normal-appearing cortex. No expression of PGRN was observed in controls, except on neurons. PGRN CSF concentrations were significantly higher in patients with relapsing-remitting MS during relapses and in progressive MS patients, compared with relapsing-remitting MS patients during remissions and with non-inflammatory controls. CONCLUSIONS: PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS.
Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Peptídeos e Proteínas de Sinalização Intercelular/análise , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Microglia/metabolismo , Microglia/patologia , ProgranulinasRESUMO
OBJECTIVE: To investigate prevalence of EMG patterns underlying hypertonia in multiple sclerosis (MS) and whether these patterns indicate different levels of spinal excitability. METHODS: We investigated the EMG activity recorded from 108 hypertonic muscles of 59 consecutive MS patients. To investigate spastic dystonia (SD), we looked for the presence of EMG activity in muscles in a resting position. To investigate dynamic stretch reflex (DSR) and static stretch reflex (SSR), we looked for the presence of EMG activity in response to a manually performed passive stretch of the muscle. RESULTS: DSR was evoked in 104 muscles. In 51 muscles, DSR was the sole EMG activity. This pattern corresponds to the classical notion of spasticity, and was predominant in extensors. In contrast, SSR was detected in 48 muscles - predominantly in flexors. SD was observed in 28 muscles, showing even distribution in flexor and extensor muscles. Only in the flexors, SSR was associated with a larger DSR compared to spasticity. CONCLUSIONS: These findings likely depend on the central effects of both flexor and extensor spindle afferents on the homonymous spinal motor neurons. SIGNIFICANCE: Improving our capacity to assess spinal excitability in MS patients.
RESUMO
Data regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing-remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and immunological predictors of early treatment response, and incidence of adverse events (AEs). One hundred and fifty-three subjects were included (93 RRMS; 84 females). Median follow-up was 1.9 (1.3-2.7). At 2-year follow-up (FU), disability worsening-free survival were 90.5%, 64.7%, and 68.8% for RRMS, primary-progressive MS (PPMS), and secondary-progressive MS (SPMS) patients, respectively. At 2-year FU, 67.1%, 72.7%, and 81.3% of patients with RRMS, PPMS, and SPMS were free of MRI activity, with NEDA-3 percentages of 62.1%, 54.6%, and 55.1%, respectively. Lower baseline EDSS was independently associated with a reduced risk of disability worsening (HR(95%CI) = 1.45(1.05-2.00), p = 0.024) and previous treatment exposure was independently associated with increased probability of radiological activity (HR = 2.53(1.05-6.10), p = 0.039). At 6-month FU, CD8 + cell decrease was less pronounced in patients with inflammatory activity (p = 0.022). Six patients (3.9%) discontinued ocrelizumab due to severe AEs. Our findings suggest that ocrelizumab is an effective treatment in real-world patients with RRMS and PMS, with a manageable safety profile. Better outcomes were observed in treatment-naïve patients and in patients with a low baseline disability level. Depletion of CD8 + cells could underlie early therapeutic effects of ocrelizumab.
Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológicoRESUMO
Neurosyphilis is still a significant medical problem in developing countries and syphilitic ocular manifestations are often not diagnosed due to the lack of typical characteristics. We describe the case of a 59-year-old homosexual man with a 1-month history of decreased vision acuity in his left eye who was diagnosed with neurosyphilis and received treatment with intravenous penicillin G (16 million units in divided daily doses), with great improvement of visual acuity and CSF examination findings. The interest of this case is not only represented by the unusually early ocular involvement, but also by the rapid evolution of the disease into the secondary stage in a man who had had one at-risk homosexual relationship only 3 months before the onset symptoms. We also support the view that the presence of ocular involvement in syphilitic patients is suggestive of involvement of the CNS and should be considered synonymous with neurosyphilis.
Assuntos
Neurossífilis/diagnóstico , Neurite Óptica/diagnóstico , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Progressão da Doença , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Neurossífilis/tratamento farmacológico , Neurossífilis/patologia , Disco Óptico/patologia , Neurite Óptica/patologia , Penicilina G/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Moderate to severe spasticity is commonly reported in Multiple Sclerosis (MS) and its management is still a challenge. Cannabinoids were recently suggested as add-on therapy for the treatment of spasticity and chronic pain in MS but there is no conclusive scientific evidence on their safety, especially on cognition and over long periods. The aim of this prospective pilot study was to assess the long-term effects of a tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray (Sativex®) on cognition, mood and anxiety. PATIENTS AND METHODS: An extensive and specific battery of neuropsychological tests (Symbol Digit Modalities Test-SDMT, California Verbal Learning Test-CVLT, Brief Visuospatial Memory Test-BVMT; PASAT-3 and 2; Free and Cued Selective Remind Test-FCSRT, Index of Sensitivity of Cueing-ISC) was applied to longitudinally investigate different domains of cognition in 20 consecutive MS patients receiving Sativex for spasticity. The primary endpoint was to assess any variation in cognitive performance. Secondary outcomes regarding mood and anxiety were investigated by means of Beck Depression Inventory (BDI) and Hamilton Anxiety Rating Scale (HAM-A). Any change in patients' spasticity was evaluated using the 0-10 Numerical Rating Scale (NRS). RESULTS: Twenty per protocol patients were followed up and evaluated at baseline, 6 and 12 months. Domains involving processing speed and auditory verbal memory significantly improved within the first 6 months of therapy (SDMT: pâ¯<â¯0.001; CVLT: pâ¯=â¯0.0001). Mood and anxiety did not show any significant variation. Additionally, the NRS score significantly improved since the beginning (pâ¯<â¯0.0001). CONCLUSIONS: These results are encouraging in supporting possible long-term benefits of Sativex on cognition and a wider role than symptom alleviator. Further studies on larger groups of patients would be necessary in order to test this intriguing possibility.