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1.
Brain ; 145(11): 3931-3942, 2022 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727945

RESUMO

Intrathecal production of kappa free light chains occurs in multiple sclerosis and can be measured using the kappa free light chain index. Kappa free light chain index values can be determined more easily than oligoclonal bands detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of oligoclonal bands, kappa free light chain index cut-offs 5.9, 6.6 and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome inception cohort. We selected patients with sufficient data to determine oligoclonal bands positivity, MRI dissemination in space and time, IgG index and sufficient quantities of paired CSF and blood samples to determine kappa free light chain indexes (n = 214). We used Kendall's Tau coefficient to estimate concordance, calculated the number of additional diagnoses when adding each positive index to dissemination in space and positive oligoclonal bands, performed survival analyses for oligoclonal bands and each index with the outcomes second attack and 2017 MRI dissemination in space and time and estimated the diagnostic properties of oligoclonal bands and the different indexes for the previously mentioned outcomes at 5 years. Oligoclonal bands were positive in 138 patients (64.5%), kappa free light chain-5.9 in 136 (63.6%), kappa free light chain-6.6 in 135 (63.1%), kappa free light chain-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between oligoclonal bands and kappa free light chain-6.6 (τ = 0.727) followed by oligoclonal bands and kappa free light chain-5.9 (τ = 0.716). Combining dissemination in space plus oligoclonal bands or kappa free light chain-5.9 increased the number of diagnosed patients by 11 (5.1%), with kappa free light chain-6.6 by 10 (4.7%), with kappa free light chain-10.61 by 9 (4.2%) and with IgG index by 3 (1.4%). Patients with positive oligoclonal bands or indexes reached second attack and MRI dissemination in space and time faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [adjusted hazard ratio (95% confidence interval)], the risk for second attack was very similar between kappa free light chain-5.9 [2.0 (0.9-4.3), P = 0.068] and kappa free light chain-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI dissemination in space and time was demonstrated with kappa free light chain-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by kappa free light chain-6.6 [3.4 (1.9-6.3), P < 0.0001]. Kappa free light chains-5.9 and -6.6 had a slightly higher diagnostic accuracy than oligoclonal bands for second attack (70.5, 71.1 and 67.8) and MRI dissemination in space and time (85.7, 85.1 and 81.0). Kappa free light chain indexes 5.9 and 6.6 performed slightly better than oligoclonal bands to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between oligoclonal bands and these indexes, we suggest using dissemination in space plus positive oligoclonal bands or positive kappa free light chain index as a modified criterion to diagnose multiple sclerosis.


Assuntos
Doenças Desmielinizantes , Esclerose Múltipla , Humanos , Bandas Oligoclonais , Cadeias kappa de Imunoglobulina , Doenças Desmielinizantes/diagnóstico , Esclerose Múltipla/diagnóstico por imagem , Imunoglobulina G
3.
Artigo em Inglês | MEDLINE | ID: mdl-38434714

RESUMO

Background: A wide variety of associated movement disorders has been described in multiple sclerosis. Phenomenology Shown: A 57-year-old woman with primary progressive multiple sclerosis developed spinal segmental myoclonus associated with focal myelitis. Educational Value: Movement disorders in multiple sclerosis are phenomenologically diverse and have varied pathophysiological mechanisms, making it essential to identify them to initiate appropriate treatment.


Assuntos
Transtornos dos Movimentos , Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Mioclonia , Doenças da Medula Espinal , Feminino , Humanos , Pessoa de Meia-Idade , Mioclonia/tratamento farmacológico , Mioclonia/etiologia , Esclerose Múltipla/complicações , Esclerose Múltipla Crônica Progressiva/complicações , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico
4.
Artigo em Inglês | MEDLINE | ID: mdl-35105687

RESUMO

BACKGROUND AND OBJECTIVES: Information about humoral and cellular responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antibody persistence in convalescent (COVID-19) patients with multiple sclerosis (PwMS) is scarce. The objectives of this study were to investigate factors influencing humoral and cellular responses to SARS-CoV-2 and its persistence in convalescent COVID-19 PwMS. METHODS: This is a retrospective study of confirmed COVID-19 convalescent PwMS identified between February 2020 and May 2021 by SARS-CoV-2 antibody testing. We examined relationships between demographics, MS characteristics, disease-modifying therapy (DMT), and humoral (immunoglobulin G against spike and nucleocapsid proteins) and cellular (interferon-gamma [IFN-γ]) responses to SARS-CoV-2. RESULTS: A total of 121 (83.45%) of 145 PwMS were seropositive, and 25/42 (59.5%) presented a cellular response up to 13.1 months after COVID-19. Anti-CD20-treated patients had lower antibody titers than those under other DMTs (p < 0.001), but severe COVID-19 and a longer time from last infusion increased the likelihood of producing a humoral response. IFN-γ levels did not differ among DMT. Five of 7 (71.4%) anti--CD20-treated seronegative patients had a cellular response. The humoral response persisted for more than 6 months in 41/56(81.13%) PwMS. In multivariate analysis, seropositivity decreased due to anti-CD20 therapy (OR 0.08 [95% CI 0.01-0.55]) and increased in males (OR 3.59 [1.02-12.68]), whereas the cellular response decreased in those with progressive disease (OR 0.04 [0.001-0.88]). No factors were associated with antibody persistence. DISCUSSION: Humoral and cellular responses to SARS-CoV-2 are present in COVID-19 convalescent PwMS up to 13.10 months after COVID-19. The humoral response decreases under anti-CD20 treatment, although the cellular response can be detected in anti-CD20-treated patients, even in the absence of antibodies.


Assuntos
COVID-19/imunologia , Imunidade Celular , Imunidade Humoral , Esclerose Múltipla/imunologia , Adulto , Idoso , Anticorpos Antivirais/análise , Antígenos CD20/imunologia , COVID-19/complicações , Feminino , Humanos , Imunoglobulina G/análise , Interferon gama/biossíntese , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Nucleocapsídeo/química , Nucleocapsídeo/imunologia , Estudos Retrospectivos
5.
J Neuropathol Exp Neurol ; 79(12): 1365-1369, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146379

RESUMO

Cocaine consumption is associated with a variety of clinical manifestations. Though cocaine intranasal inhalation always determines nasal mucosal damages, extensive septum perforations, and midline destructions-known as cocaine-induced midline destructive lesions (CIMDL)-affect only a limited fraction of patients. CIMDL is viewed as a cocaine-associated autoimmune phenomenon in which the presence of atypical anti-neutrophil cytoplasmic antibody (ANCA) promotes and/or defines the disease phenotype. A 51-year-old man presented with an intracranial tumor-like lesion by its space-occupying effect. CT also revealed the destruction of the nasal septum and skull base. A diagnosis of CIMDL was made in light of the patient's history as well as findings of the physical and endoscopic examinations, imaging studies, and laboratory testing. There was no evidence of other pathologies. Histopathological results from cerebral biopsy led us to consider the intracranial pathology as an extension of the CIMDL. CIMDL is the result of a necrotizing inflammatory tissue response triggered by cocaine abuse in a subset of predisposed patients. The reported case is the first CIMDL consistent with brain extension mimicking a tumor-like lesion. While the presence of atypical ANCA seems to promote and/or define the disease phenotype, the specific role of these and other circulating autoantibodies needs further investigation.


Assuntos
Lesões Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Lesões Encefálicas/etiologia , Transtornos Relacionados ao Uso de Cocaína/complicações , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
6.
Neurology ; 95(15): e2109-e2118, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32641525

RESUMO

OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.


Assuntos
Infecções por Coronavirus/fisiopatologia , Doença de Parkinson Pós-Encefalítica/fisiopatologia , Pneumonia Viral/fisiopatologia , Putamen/diagnóstico por imagem , Betacoronavirus , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , COVID-19 , Transtornos da Consciência , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Progressão da Doença , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Eletroencefalografia , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/etiologia , Hipocinesia/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rigidez Muscular/diagnóstico por imagem , Rigidez Muscular/etiologia , Rigidez Muscular/fisiopatologia , Nortropanos , Transtornos da Motilidade Ocular , Pandemias , Doença de Parkinson Pós-Encefalítica/diagnóstico por imagem , Doença de Parkinson Pós-Encefalítica/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Putamen/metabolismo , SARS-CoV-2 , Tomografia Computadorizada de Emissão de Fóton Único
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