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1.
Clin Biochem ; 97: 82-84, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34450126

RESUMO

BACKGROUND: Anti-Sry-like high mobility group box 1 (anti SOX-1) proteins are rare onconeural antibodies associated with paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS). Few patients with anti-SOX-1 antibodies and negative anti-glial nuclear antibody reactivity have been described to date. CASE SUBJECT AND METHODS: Our case involves a 72-year-old female patient with progressive girdle weakness, sensation of heaviness in the lower limbs, predominantly distal and associated with circulatory problems together with instability when walking, with a high suspicion of an autoimmune myopathic disorder. Immunoblot test for autoimmune myopathies antibodies detection were all negative. Onconeuronal antibodies were determined in serum by indirect immunofluorescence being negative as well. Given the high suspicion, we also checked for the presence of other antineuronal antibodies whose patterns are not visible by IIF. RESULTS: Onconeuronal antibodies by immunoblot for the following antibodies: Hu, Ri, Yo, Zic4, Tr, PCA-2, MA-TA, CV2, GAD65, Zic4, Titin, SOX1, Recoverin and Amp, revealed an unexpected clear band in SOX-1, which are highly suggestive of paraneoplastic LEMS. DISCUSSION: We hypothesize that discordant onconeuronal antibodies results were due to the fact that positivity in IIF is associated with other SOX-B group proteins (normally related to cases of non-paraneoplastic neuropathy), while negativity in IIF and subsequent confirmed presence of specific SOX1 antibody by immunoblot could indicate an underlying tumor.


Assuntos
Anticorpos/sangue , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Fatores de Transcrição SOXB1/imunologia , Idoso , Feminino , Humanos , Síndrome Miastênica de Lambert-Eaton/sangue
2.
J Immunol Methods ; 496: 113102, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298066

RESUMO

BACKGROUND: In this study, we assessed the performance characteristics of a laboratory-developed radioimmunoassay (RIA) to detect N-type voltage-gated calcium channel (N-VGCC) antibodies found in several autoimmune neurologic diseases. METHODS: Four hundred and forty-five (n = 445) sera were evaluated, including 156 sera (50 positive and 106 negative for N-VGCC antibodies) previously tested at Mayo Clinic Laboratories (MCL) and 289 controls (n = 187 disease and n = 102 healthy). Specimens were analyzed with the RIA using N-VGCC labeled with 125I-ω-conotoxin GVIA. The RIA was compared to the predicate MCL assay using a tiered positive predictive value (PPV) approach. Other performance characteristics evaluated included specificity, precision, interference, and stability. RESULTS: Qualitative inter-laboratory agreement based on tiered PPVs was 100% for results >1.00 nmol/L (71% PPV), 48% for results of 0.10-0.99 nmol/L (24% PPV) and 22% for results of 0.04-0.10 nmol/L (19% PPV). Negative results showed 90% agreement (n = 106). Specificity in controls positive for other neural autoantibodies and healthy controls were 87% and 100%, respectively. Acceptable results were observed for other performance characteristics. CONCLUSIONS: Inter-laboratory correlations demonstrate equivalence between assays with some discrepancies between low positive results. Collaborative efforts aimed at assessing the clinical spectrum associated with these antibodies and consensus for harmonizing test performance are required for optimal categorization of patients.


Assuntos
Autoanticorpos/sangue , Autoimunidade , Canais de Cálcio Tipo N/imunologia , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Radioimunoensaio , Testes Sorológicos , Adulto , Idoso , Especificidade de Anticorpos , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
4.
Thorac Cancer ; 11(2): 465-469, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31880403

RESUMO

Paraneoplastic neurological syndromes (PNS) are rare disorders affecting any part of the central, peripheral or autonomic nervous system that occur in association with cancer. Among cancer patients, less than 1% overall develop PNS. Anti-SOX1 antibodies' positive paraneoplastic neurological disorders are rare and are usually associated with small cell lung cancer (SCLC). Here, we report a case of a 61-year-old male patient who presented with an unusual anti-SOX1 positive PNS. The right tibialis anterior showed noticeable low-amplitude motor unit potentials and high amplitude motor potentials in electrodiagnostic study, suggesting the presence of Lambert-Eaton myasthenic syndrome (LEMS). Typical MRI and PET-CT found a hyperintense lesion with contrast enhancement in the thorax in front of 5-6 centrum of vertebrae, and thoracoscopic biopsy revealed pathological findings for SCLC. The patient underwent several lines of chemotherapy and radiotherapy and survived for 15 months after the diagnosis of SCLC.


Assuntos
Autoanticorpos/sangue , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Neoplasias Pulmonares/diagnóstico , Doenças do Sistema Nervoso/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Fatores de Transcrição SOXB1/imunologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Autoanticorpos/imunologia , Diagnóstico Diferencial , Humanos , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/complicações , Síndrome Miastênica de Lambert-Eaton/imunologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/imunologia , Prognóstico , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/imunologia
5.
BMJ Case Rep ; 12(7)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315840

RESUMO

Paraneoplastic syndromes (PS) are a rare presentation of cancer, most commonly associated with small cell lung cancer (SCLC), breast cancer and haematologic malignancies. The diagnosis of PS is challenging because it could affect multiple organ systems and it may present before the tumour is visible by imaging. We report a malignant tumour diagnosed in a male patient who referred long-term paraesthesia and proximal muscle strength loss. After ruling out common causes of polyneuropathy, the anti-SOX1 antibody gave light to the diagnosis. A pulmonary opacity in the upper right lobe was observed in the chest X-ray and a pulmonary tumour was later confirmed by CT scan. The biopsy of the cervical lymphadenopathy determined an SCLC, which caused a PS called Lambert-Eaton myasthenic syndrome (LEMS). Our case raises awareness of a rare PS presentation, which can be diagnosed by specific antibodies, allowing early diagnosis and treatment of lung cancer.


Assuntos
Síndrome Miastênica de Lambert-Eaton/sangue , Síndromes Paraneoplásicas/diagnóstico , Parestesia/etiologia , Fatores de Transcrição SOXB1/antagonistas & inibidores , Carcinoma de Pequenas Células do Pulmão/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/sangue , Diagnóstico Diferencial , Eletromiografia/métodos , Humanos , Síndrome Miastênica de Lambert-Eaton/complicações , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Masculino , Síndromes Paraneoplásicas/fisiopatologia , Fatores de Transcrição SOXB1/sangue , Biópsia de Linfonodo Sentinela/métodos , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
6.
J Neurol ; 265(9): 2114-2119, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29987589

RESUMO

As testing for neuronal antibodies become more readily available, the spectrum of conditions potentially associated with these autoantibodies has been widening. Voltage-gated calcium channel antibodies (VGCC-Ab) are no exception to this trend. The significance of an elevated VGCC-Ab titer beyond its original clinicopathological correlate, Lambert-Eaton myasthenic syndrome (LEMS) remains undetermined. We sought to determine the diagnostic significance of an elevated serum VGCC-Ab titer in a large single-center cohort of 100 patients. The majority of patients (58%) with elevated VGCC-Ab levels lacked an inflammatory or autoimmune etiology of their neurologic diagnosis. Only six cases (6%) of LEMS and two cases (2%) of SCLC (without LEMS) were identified. No significant differences in antibody titers were seen between the autoimmune and non-autoimmune groups. These findings support the notions that: (a) elevated VGCC-Ab titers without clinical correlation must be interpreted with caution, and (b) the clinical and electrodiagnostic criteria for LEMS should remain the mainstay in the diagnosis of LEMS.


Assuntos
Especificidade de Anticorpos/imunologia , Autoanticorpos/sangue , Canais de Cálcio/imunologia , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
PLoS One ; 13(3): e0193723, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29518096

RESUMO

Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA). We also included 8 patients with ocular MG, 3 with Lambert-Eaton myasthenic syndrome, 5 with motor neuron disease, and 9 with other diagnoses as comparators for the serological testing. Antibodies were identified in 25/62 (40.3%) patients: 7 had antibodies to clustered AChR, 17 to MuSK, and 2 to LRP4. Three patients were double seropositive: 1 for MuSK and LRP4, and 2 for MuSK and clustered AChR. The patients with MuSK antibodies were mostly female (88.2%) and characterized by predominantly bulbar involvement (70%) and frequent myasthenic crises (58.3%). The patients with antibodies to clustered AChR, including 2 with ocular MG, tended to have a mild phenotype and good prognosis.


Assuntos
Autoanticorpos/sangue , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Adulto , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Proteínas Relacionadas a Receptor de LDL/imunologia , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/imunologia , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/sangue , Doença dos Neurônios Motores/imunologia , Ensaio de Radioimunoprecipitação , Receptores Proteína Tirosina Quinases/imunologia , República da Coreia , Estudos Retrospectivos
8.
CPT Pharmacometrics Syst Pharmacol ; 6(9): 625-634, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28623849

RESUMO

Lambert-Eaton myasthenia (LEM) is a rare autoimmune disorder associated with debilitating muscle weakness. There are limited treatment options and 3,4-diaminopyridine (3,4-DAP) free base is an investigational orphan drug used to treat LEM-related weakness. We performed a population pharmacokinetic/pharmacodynamic (PK/PD) analysis using 3,4-DAP and metabolite concentrations collected from a phase II study in patients with LEM. The Triple Timed Up & Go (3TUG) assessment, which measures lower extremity weakness, was the primary outcome measure. A total of 1,270 PK samples (49 patients) and 1,091 3TUG data points (32 randomized patients) were included in the PK/PD analysis. A two-compartment and one-compartment model for parent and metabolite, respectively, described the PK data well. Body weight and serum creatinine partially explained the variability in clearance for the final PK model. A fractional inhibitory maximum effect (Emax ) model characterized the exposure-response relationship well. The PK/PD model was applied to identify a suggested dosing approach for 3,4-DAP free base.


Assuntos
4-Aminopiridina/análogos & derivados , Síndrome Miastênica de Lambert-Eaton/tratamento farmacológico , Modelos Biológicos , Debilidade Muscular/tratamento farmacológico , Bloqueadores dos Canais de Potássio , 4-Aminopiridina/sangue , 4-Aminopiridina/farmacocinética , 4-Aminopiridina/farmacologia , 4-Aminopiridina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Amifampridina , Arilamina N-Acetiltransferase/genética , Feminino , Humanos , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/fisiopatologia , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/sangue , Debilidade Muscular/genética , Debilidade Muscular/fisiopatologia , Polimorfismo de Nucleotídeo Único , Bloqueadores dos Canais de Potássio/sangue , Bloqueadores dos Canais de Potássio/farmacocinética , Bloqueadores dos Canais de Potássio/farmacologia , Bloqueadores dos Canais de Potássio/uso terapêutico , Resultado do Tratamento , Adulto Jovem
9.
Artigo em Russo | MEDLINE | ID: mdl-28638036

RESUMO

The authors studied two patients with Lambert-Eaton myasthenic syndrome (LEMS) in whom the repeated examination did not find specific of LEMS P/Q type voltage-gates calcium channel autoantibodies. The results of clinical testing and electrophysiological examination showed the typical character of movement disorders with the absence of tendon reflexes and signs of disautonomia as well as a decrease in M-response amplitude and phenomena of decrement with low frequency- and increment with high frequency stimulation. Both patients revealed no signs of paraneoplastic process. Autoimmune character of the damage was confirmed by the effectiveness of treatment with glucocorticoid hormones.


Assuntos
Síndrome Miastênica de Lambert-Eaton/diagnóstico , Autoanticorpos/sangue , Autoimunidade , Canais de Cálcio Tipo P/imunologia , Canais de Cálcio Tipo Q/imunologia , Eletrodiagnóstico , Fenômenos Eletrofisiológicos , Glucocorticoides/uso terapêutico , Humanos , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/tratamento farmacológico , Síndrome Miastênica de Lambert-Eaton/fisiopatologia , Masculino , Pessoa de Meia-Idade
10.
Muscle Nerve ; 51(2): 176-84, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24862203

RESUMO

INTRODUCTION: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune presynaptic neuromuscular disorder. Autoantibodies against subunits of voltage-gated calcium channels (VGCCs) associated with acetylcholine release are thought to cause LEMS. METHODS: HEK293 cells expressing specific individual recombinant subunits of α(1A), α(1B), α(1C), and α(1E); ß(3); and α(2)δ of human neuronal VGCCs were exposed to antibodies from 3 LEMS patients, 1 patient with small-cell lung carcinoma, and 1 with myasthenia gravis. RESULTS: All LEMS patient antibodies bound to cells containing any of the α(1) or ß(3) subunits alone or combined with α(2)δ subunits, but not α(2)δ alone. Autoantibodies from the patient with small-cell lung carcinoma but not the myasthenia gravis patient targeted the same VGCC subunits. CONCLUSIONS: Autoantibodies from LEMS patients bind directly to multiple VGCC α(1) subunits as well as the ß(3) subunit. Thus, multiple components of the presynaptic VGCC complex are prospective targets for antibodies in LEMS.


Assuntos
Autoanticorpos/imunologia , Canais de Cálcio/imunologia , Canais de Cálcio/metabolismo , Síndrome Miastênica de Lambert-Eaton/imunologia , Subunidades Proteicas/metabolismo , Canais de Cálcio/genética , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Pequenas/imunologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Síndrome Miastênica de Lambert-Eaton/sangue , Subunidades Proteicas/genética , Transfecção
11.
Clin Neurophysiol ; 125(12): 2328-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25065299

RESUMO

Lambert-Eaton myasthenic syndrome (LEMS) describes a rare human autoimmune disorder of the neuromuscular junction (NMJ). Clinically, LEMS patients suffer from characteristic muscle weakness that is caused by the presence of antibodies directed against their voltage-gated calcium channels (VGCC). These channels are localized in the presynaptic membrane of their motor nerve terminals. Binding of autoimmune antibodies to the VGCCs leads to reduced neuromuscular transmission. In approximately 50% of the patients, LEMS is reflected by a paraneoplastic manifestation and most commonly associated with a small cell lung carcinoma (SCLC) whose cells also express VGCCs in their plasma membrane. Better understanding of the pathophysiological mechanisms of LEMS has helped with the development of new diagnostic approaches and has led to targeted symptomatic and immunosuppressive therapy. For LEMS patients with an underlying malignancy, tumor therapy is the first choice to date.


Assuntos
Antineoplásicos , Imunoterapia , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Síndrome Miastênica de Lambert-Eaton/terapia , Animais , Antineoplásicos/uso terapêutico , Autoanticorpos/sangue , Humanos , Imunoterapia/métodos , Síndrome Miastênica de Lambert-Eaton/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Junção Neuromuscular/metabolismo , Junção Neuromuscular/patologia , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/terapia
12.
J Neuroimmunol ; 273(1-2): 115-6, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24929678

RESUMO

Antibodies (abs) to the GABAB receptor have been recently found to be responsible for immune-mediated encephalitis with dominant seizures. They are in approximately 50% of cases associated with small-cell lung cancer (SCLC). GABAB receptors are mainly located in the hippocampus, thalamus and cerebellum in the presynaptic and postsynaptic regions of synapses. The main function of these receptors is to reduce activity states of neurons. In some instances, GABAB receptor abs in these patients were accompanied by other antibodies, among them VGCC abs (Lancaster et al., 2010, Boronat et al., 2011). VGCC abs cause paraneoplastic Lambert Eaton myasthenic syndrome (LEMS) by reduction of presynaptic VGCCs (Titulaer et al., 2011). In the domain of CNS disease, VGCC abs have been found in association with paraneoplastic cerebellar ataxia (Mason et al., 1997) and rarely and at low titres also in other paraneoplastic encephalopathies together with Hu abs (Lennon et al., 1995). It has been a long-standing debate if abs in paraneoplastic conditions associate rather with the neurological syndrome or the tumour. Here, we describe the conjoint occurrence of abs to the GABAB receptor and to the VGCC in a patient with SCLC presenting only symptoms of the peripheral nervous system giving another example of the latter hypothesis.


Assuntos
Anticorpos/metabolismo , Canais de Cálcio/imunologia , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/imunologia , Receptores de GABA-B/imunologia , Feminino , Fluordesoxiglucose F18 , Humanos , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Síndrome Miastênica de Lambert-Eaton/tratamento farmacológico , Músculo Esquelético/metabolismo , Tomografia por Emissão de Pósitrons , Receptores de GABA-B/metabolismo , Tomógrafos Computadorizados
13.
J Neurol Sci ; 336(1-2): 169-70, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24215945

RESUMO

Non-paraneoplastic cerebellar ataxia associated with voltage-gated calcium channel (VGCC) antibodies is a rare entity with only few cases reported in literature. We describe a 60 year-old man with subacute cerebellar ataxia and subclinical Lambert-Eaton myasthenic syndrome (LEMS) in whom VGCC antibodies were detected at high titer in serum and cerebrospinal fluid. Screening for underlying malignancies was negative. Intravenous immunoglobulin treatment led to the improvement of clinical picture and reduction of serum antibody titer over a 13-month follow-up period. We emphasize that VGCC antibodies should be included in the diagnostic work-up of patients with subacute cerebellar ataxia and that treatment with IVIG can improve the clinical picture and prevent disability.


Assuntos
Autoanticorpos/sangue , Canais de Cálcio/sangue , Ataxia Cerebelar/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome Miastênica de Lambert-Eaton/sangue , Autoanticorpos/biossíntese , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Síndrome Miastênica de Lambert-Eaton/diagnóstico , Síndrome Miastênica de Lambert-Eaton/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
Atheroscler Suppl ; 14(1): 219-22, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23357168

RESUMO

Autoimmune ion channel disorders of the peripheral nervous system include myasthenia gravis, the Lambert-Eaton myasthenic syndrome, acquired neuromyotonia and autoimmune autonomic ganglionopathies. These disorders are characterized by the common feature of being mediated by IgG autoantibodies against identified target antigens, i.e. the acetylcholine receptor, the voltage-gated calcium and potassium channels, and the neuronal acetylcholine receptor. Moreover, experimental animal models have been identified for these diseases that respond to immunotherapy and are improved by plasmapheresis. On this basis, autoimmune ion channel disorders represent the ideal candidate for therapeutic apheresis. Immunoadsorption can be the treatment of choice when intensive apheretic protocols or long-term treatments must be performed, in patients needing frequent apheresis to keep a stable clinical condition, in case of unresponsiveness to corticosteroids and immunosuppressive treatments, or failure with TPE or intravenous immunoglobulins, and in patients with severe contraindications to long-term corticosteroids.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes do Sistema Nervoso/terapia , Autoimunidade , Remoção de Componentes Sanguíneos/métodos , Técnicas de Imunoadsorção , Imunoadsorventes/uso terapêutico , Canais Iônicos/imunologia , Doenças do Sistema Nervoso Periférico/terapia , Adsorção , Doenças Autoimunes do Sistema Nervoso/sangue , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso Autônomo/sangue , Doenças do Sistema Nervoso Autônomo/imunologia , Doenças do Sistema Nervoso Autônomo/terapia , Biomarcadores/sangue , Humanos , Imunoglobulina G/sangue , Síndrome de Isaacs/sangue , Síndrome de Isaacs/imunologia , Síndrome de Isaacs/terapia , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/imunologia , Síndrome Miastênica de Lambert-Eaton/terapia , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/imunologia , Resultado do Tratamento
16.
Autoimmun Rev ; 8(7): 549-51, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19393214

RESUMO

Paraneoplastic neurological syndromes (PNS) are tumour-associated disorders, which are not caused by the tumour itself or its metastases. Since antineuronal autoantibodies can be detected in these patients, an autoimmune pathogenesis is suspected. Recently, autoantibodies against cerebellar Bergmann glia were found in patients with paraneoplastic Lambert-Eaton myasthenic syndrome and other paraneoplastic neurological syndromes associated with small cell lung cancer, and SOX1 has been identified as the corresponding antigen. SOX1-antibodies have been reported to be highly specific for paraneoplastic neurological disorders. However, increasing evidence exists that they may also be associated with other neuroimmunological disorders without an underlying tumour.


Assuntos
Autoanticorpos/imunologia , Síndromes Paraneoplásicas do Sistema Nervoso/imunologia , Fatores de Transcrição SOXB1/imunologia , Autoanticorpos/sangue , Cerebelo/imunologia , Cerebelo/metabolismo , Humanos , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/imunologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neuroglia/imunologia , Neuroglia/metabolismo , Síndromes Paraneoplásicas do Sistema Nervoso/sangue , Fatores de Transcrição SOXB1/metabolismo , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/metabolismo
17.
J Neuroimmunol ; 204(1-2): 136-9, 2008 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-18809213

RESUMO

OBJECTIVE: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which the transmission across the neuromuscular junction is disturbed by autoantibodies directed against the presynaptic P/Q-type voltage-gated calcium channels (VGCC). LEMS is paraneoplastic (T-LEMS) in about 60% of patients mostly associated with a small cellular lung carcinoma (SCLC), but occurs spontaneously without a tumor in 40% (NT-LEMS). In most cases neurologic symptoms appear before tumor diagnosis, but there is as yet no clear specific serologic marker to distinguish between NT- and T-LEMS. METHODS: To see whether antibodies from patients with NT- and T-LEMS differentially recognize antigenic sites of the alpha 1A subunit of P/Q-type VGCC, we studied serum samples from 22 T-LEMS and 24 NT-LEMS patients. Sera reactivity was tested by Western blot analysis to recombinant proteins corresponding to the extracellular S5-S6 linker region of three out of four domains forming the alpha 1 subunit of P/Q-type VGCC. RESULTS: Sera from 9/24 (37,5%) NT-LEMS patients, but only 1/22 (4,6%) T-LEMS patients recognized domain IV (p=0,011). Seroreactivity to domains I and III was similar for NT-LEMS and T-LEMS patients (domain I: 8%/14%; domain III: 46%/41%, not significant). CONCLUSIONS: These data suggest that an antibody response to domain IV is more common in LEMS without tumor than in paraneoplastic LEMS. This may have implications for diagnostic workup in LEMS patients without previously established diagnosis of a tumor. Additionally this could point towards a differential autoimmune pathogenesis between T-LEMS and NT-LEMS.


Assuntos
Autoanticorpos/sangue , Canais de Cálcio Tipo N/imunologia , Síndrome Miastênica de Lambert-Eaton/sangue , Neoplasias Pulmonares/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Feminino , Humanos , Síndrome Miastênica de Lambert-Eaton/complicações , Masculino , Pessoa de Meia-Idade , Estrutura Terciária de Proteína
18.
J Neuroimmunol ; 201-202: 104-10, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18644634

RESUMO

We investigated the effect of IgG immunoadsorption (IA) on cytokine network in patients with treatment-resistant Myasthenia Gravis (MG) and Lambert-Eaton Syndrome (LEMS). We observed upregulation of interleukin (IL)-10, an anti-inflammatory and B cells growth factor, and reduction of pro-inflammatory factors such as IL-18 and IL-17, in both MG and LEMS after IA. Our observation suggests that the massive removal of antibodies might induce modifications of the cytokine balance linked to T and B cells mediated autoimmunity.


Assuntos
Citocinas/sangue , Imunoglobulina G/sangue , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/terapia , Miastenia Gravis/sangue , Miastenia Gravis/terapia , Adolescente , Adulto , Canais de Cálcio Tipo P/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Seguimentos , Humanos , Técnicas de Imunoadsorção , Síndrome Miastênica de Lambert-Eaton/imunologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/imunologia , Radioimunoensaio/métodos , Receptores Colinérgicos/imunologia
20.
J Neurol Sci ; 270(1-2): 194-6, 2008 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-18374949

RESUMO

Lambert-Eaton myasthenic syndrome (LEMS) is an immune-mediated disorder of the neuromuscular junction that rarely is associated with cerebellar ataxia (CA). We describe two patients with non-paraneoplastic LEMS associated with CA who showed high levels of anti-P/Q-type voltage-gated calcium channels antibodies in the serum and cerebrospinal fluid, and reduced CMAP with increment after brief maximum voluntary contraction in electrophysiological studies. We suggest that LEMS should be considered in the differential diagnosis of patients with CA.


Assuntos
Ataxia Cerebelar/complicações , Síndrome Miastênica de Lambert-Eaton/complicações , Potenciais de Ação/fisiologia , Adulto , Anticorpos/sangue , Canais de Cálcio/imunologia , Ataxia Cerebelar/sangue , Ataxia Cerebelar/líquido cefalorraquidiano , Ataxia Cerebelar/tratamento farmacológico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome Miastênica de Lambert-Eaton/sangue , Síndrome Miastênica de Lambert-Eaton/líquido cefalorraquidiano , Síndrome Miastênica de Lambert-Eaton/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Condução Nervosa/fisiologia , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/complicações
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