The Lambert-Eaton Myasthenic Syndrome

O’Neill, Jane; Murray, N.M.F.; Newsom‐Davis, John

doi:10.1093/brain/111.3.577

Cited by 652 publications

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“…An HLA association with HLA B8DR3 suggests an underlying genetic predisposition to autoimmunity [65] and these patients often have other autoimmune disorders, such as thyroid disease or diabetes. [64] These observations led to the first experimental studies implicating the immune system. It was shown that patients with LEMS responded clinically to plasma exchange, and daily injection of LEMS IgG antibodies into mice reproduced the principal neurophysiologic changes of LEMS.…”

Section: Immunological Basismentioning

confidence: 99%

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Autoimmune disorders of the neuromuscular junction

Lang

Vincent

2009

Current Opinion in Pharmacology

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The neuromuscular junction (NMJ) is a prototypic synapse although its structure is rather different from those of the central nervous system (CNS). The unmyelinated motor nerve terminals are separated from the postsynaptic membrane by a cleft that contains a basal lamina. This includes many proteins such as collagens, laminins, fibronectin and perlecan which help anchor some of the key elements involved in NMJ The neuromuscular junction (NMJ) is a specialized synapse with a complex structural and functional organization. It is a target for a variety of immunological disorders and these diseases usually respond well to immunotherapies. The understanding of the immunological basis of myasthenia gravis, the most common neuromuscular junction disorder, has improved in the recent years. Most patients have antibodies to the acetylcholine receptor (AChR), but around 10% have AChR antibodies that are only identified by novel methods, and up to 5% have muscle-speciÞ c kinase antibodies which deÞ ne a different subgroup of myasthenia. The spectrum of antibodies and their pathophysiological aspects are being elucidated. Even though less common, Lambert Eaton myasthenic syndrome (LEMS) is important to recognize. The abnormality in LEMS is a presynaptic failure to release enough packets of ACh, caused by antibodies to the presynaptic voltage-gated calcium channels. More than half these patients have a small cell carcinoma of lung. Acquired neuromyotonia (NMT) is a condition associated with muscle hyperactivity. Clinical features include muscle stiffness, cramps, myokymia, pseudomyotonia and weakness. The immune mechanisms of acquired NMT relate to loss of voltage-gated potassium channel function. This review will focus on the important recent developments in the immunemediated disorders of the NMJ.Key words: Gravis, Lambert Eaton myasthenic syndrome, neuromyotonia, neuromuscular junction, autoimmunity, acetylcholine receptor, voltage-gated channel development and function; for instance acetylcholine esterase (AChE) is localized via ColQ, a collagen-like molecule, to the basal lamina. Agrin and neuregulins, secreted from the nerve terminal, are bound by the basal lamina and interact with their receptors, playing an important role in the location of postsynaptic membrane proteins, voltage-gated calcium channels and the dystroglycans. The postsynaptic membrane at the NMJ forms a series of deep folds. The acetylcholine receptors (AChRs) are found at the top one-third of these folds, whereas the voltage-gated sodium channels are anchored at the bottom of the folds. The development of the NMJ is a fascinating area of research [1] and many of the proteins involved are relevant to disease ([ Figure 1] for a simple representation).The nerve action potential opens voltage-gated calcium channels (VGCCs) that are located in the motor nerve terminal [ Figure 1]. The resulting influx of calcium leads to the release of about 30 (in human muscle) individual packets of acetylcholine (ACh). Some of the ACh is hydrolysed by AChE but about 65%...

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Section: Immunological Basismentioning

confidence: 99%

“…[64] Typically, weakness improves during sustained effort as can be shown clinically or by electromyography. The compound muscle action potential is very small but increases during high-frequency stimulation or following a brief period of voluntary contraction.…”

Section: Vincent: Neuromuscular Autoimmunitymentioning

confidence: 99%

Autoimmune disorders of the neuromuscular junction

Lang

Vincent

2009

Current Opinion in Pharmacology

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“…To define the clinical associations with AGNA, we studied the serum of 113 patients without PNS and SCLC, 122 with other cancer types, and 19 with idiopathic LEMS, defined by the absence of cancer after at least 3 years of follow-up (O'Neill et al, 1988). To ascertain the frequency of AGNA among different PNS associated with SCLC, we reviewed the presence of AGNA immunoreactivity in 30 patients with paraneoplastic LEMS, 27 with paraneoplastic cerebellar degeneration (PCD), 10 with sensory neuropathy, 10 with opsoclonus, and 8 with limbic encephalitis.…”

Section: Patientsmentioning

confidence: 99%

Anti-glial nuclear antibody: Marker of lung cancer-related paraneoplastic neurological syndromes

Graus

Vincent

Pozo‐Rosich

et al. 2005

Journal of Neuroimmunology

122

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We describe a new antibody, called anti-glial nuclear antibody (AGNA), in patients with paraneoplastic neurological syndromes (PNS) and small-cell lung carcinoma (SCLC). AGNA was initially identified in 24 sera of our archives by immunohistochemistry on rat cerebellum. AGNA positive sera showed a characteristic nuclear staining of the Bergmann glia in the Purkinje cell layer. Immunoblots and probing a cerebellar expression library with AGNA sera did not identify the antigen. Twenty of the 24 patients with AGNA had PNS and all but two had lung cancer. AGNA was identified in 13/113 (11.5%) patients with SCLC compared with 0/122 with other types of cancer (p <0.0001). The frequency of AGNA was not higher than expected for the presence of SCLC in the different PNS subtypes except in LEMS (p =0.0002). AGNA was present in 13/30 (43%) of LEMS patients with SCLC, compared with 0/19 of LEMS patients without cancer (p =0.0006). We conclude that the recognition of AGNA is helpful since this antibody is found in PNS associated with SCLC, particularly LEMS, in which other onconeural antibodies are absent.

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“…Autonomic dysfunctions, mostly xerostomia, occur in approximately 80% of the patients; other symptoms include impotence in men and loss of the libido in women 2,11 . Both patients in this report presented xerostomia and reduction of the libido.…”

Section: Discussionmentioning

confidence: 99%

“…Over 50% of the cases are related with oat cell lung carcinoma [1][2][3] . Lambert-Eaton syndrome has also been associated with squamous cell lung carcinoma, mixed tumors of the parotid glands, systemic mastocytosis, sarcomas, kidney carcinoma and other malignant neoplastic diseases [3][4][5] .…”

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confidence: 99%

Lambert-Eaton myasthenic syndrome: report of two cases

Scola

Iwamoto²,

Ramos³

et al. 1998

Arq. Neuro-Psiquiatr.

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-Two cases of Lambert-Eaton myasthenic syndrome, in female patients whose neoplasm investigation was negative, are reported. Repetitive stimulation of ulnar nerve showed an incremental response (+187% and +198%). Needle EMG was normal in one of them, however, the other patient showed fibrillation potentials, positive sharp waves, potentials of low amplitude and short duration. The authors discuss the clinical, electrophysiological, and pathological features of the disease, as well as some aspects of the treatment and follow-up of these patients.KEY WORDS: Lambert-Eaton myasthenic syndrome, neurophysiological study, muscular biopsy, treatment. Síndrome miastênica de Lambert-Eaton: relato de dois casosRESUMO -São descritos dois casos de síndrome miastênica de Lambert-Eaton em pacientes do sexo feminino, nas quais a investigação de neoplasias foi negativa. Os testes de estimulação repetitiva mostraram incrementos de 187 e 198%. A eletromiografia de agulha em um dos casos foi normal e no outro mostrou potenciais de fibrilação, ondas agudas positivas de curta duração e baixa amplitude de potenciais. São discutidos aspectos clínicos, neurofisiológicos, biópsia muscular, tratamento e acompanhamento desta condição rara. PALAVRAS-CHAVE: síndrome miastênica de Lambert-Eaton, estudo neurofisiológico, biópsia muscular, tratamento.Lambert-Eaton myasthenic syndrome is a rare condition, resulting from an acetylcholine release deficiency in the neuromuscular junction. Over 50% of the cases are related with oat cell lung carcinoma 1-3 . Lambert-Eaton syndrome has also been associated with squamous cell lung carcinoma, mixed tumors of the parotid glands, systemic mastocytosis, sarcomas, kidney carcinoma and other malignant neoplastic diseases [3][4][5] . As Lambert-Eaton syndrome presents mostly as a paraneoplastic condition, an extensive investigation of malignant tumors should be performed. However, approximately 40% of the patients do not show any evidence of cancer, and in these cases, the disease is considered to be of primary autoimmune origin 1,2 .We report two cases of Lambert-Eaton myasthenic syndrome in female patients whose investigation for neoplastic diseases was negative, and due to the rarity of this type of disease, we found it worth putting on record.

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The Lambert-Eaton Myasthenic Syndrome

Cited by 652 publications

References 0 publications

Autoimmune disorders of the neuromuscular junction

Autoimmune disorders of the neuromuscular junction

Anti-glial nuclear antibody: Marker of lung cancer-related paraneoplastic neurological syndromes

Lambert-Eaton myasthenic syndrome: report of two cases

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