Non-paraneoplastic Lambert-Eaton Myasthenic Syndrome Research Articles

A Unique Case of Non-paraneoplastic Lambert-Eaton Myasthenic Syndrome Treated with Subcutaneous Immunoglobulin (P11-11.019)

A Unique Case of Non-paraneoplastic Lambert-Eaton Myasthenic Syndrome Treated with Subcutaneous Immunoglobulin (P11-11.019)

Teaching Video NeuroImage: Reflex Facilitation in Lambert-Eaton Myasthenic Syndrome.

A 41-year-old woman presented with progressive fluctuating lower limb weakness, urinary incontinence, and dry eyes and mouth. Physical examination revealed proximal flaccid tetraparesis (Medical Research Council 4). The patellar reflex was absent, but with postexercise facilitation (video 1). Eyelid and eye movements were normal. Electroneuromyography revealed a presynaptic neuromuscular junction disorder (figure). Antibodies to anti-voltage-gated calcium channels were positive. Periodic cancer screening, including whole-body FDG-PET, was negative during 2 years of follow-up. These findings were consistent with nonparaneoplastic Lambert-Eaton myasthenic syndrome.1 The patient had a good response to IV immunoglobulin. The presence of ascending muscle weakness, autonomic dysfunction, and postexercise facilitation of reflexes should raise suspicion for the diagnosis.

Non-paraneoplastic Lambert-Eaton myasthenic syndrome presenting dropped head and respiratory failure with normoreflexia

A 57-year-old woman developed insidious dropped head, respiratory failure and autonomic dysfunction with inconspicuous limb weakness, but without diminished deep tendon reflexes. Progressive myopathy affecting truncal muscles was initially suspected, but non-paraneoplastic Lambert–Eaton myasthenic syndrome was finally diagnosed based on the results of electrophysiological studies and positivity for anti-P/Q-type voltage-gated calcium channel antibody without any evidence of malignancy. In general, most patients with Lambert–Eaton myasthenic syndrome have more than one of the core manifestations of Lambert–Eaton myasthenic syndrome including proximal-dominant limb weakness, diminished or absent deep tendon reflexes and autonomic dysfunction. However, this patient presented atypical manifestations, and lacked two core manifestations except for autonomic dysfunction. It is important to take Lambert–Eaton myasthenic syndrome into consideration in the differential diagnosis of patients showing atypical presentation, such as dropped head or respiratory failure, when they have only one core manifestation of Lambert–Eaton myasthenic syndrome.

Voltage gated calcium channel antibody-related neurological diseases.

Voltage gated calcium channel (VGCC) antibodies are generally associated with Lambert-Eaton myasthenic syndrome. However the presence of this antibody has been associated with paraneoplastic as well as non-paraneoplastic cerebellar degeneration. Most patients with VGCC-antibody-positivity have small cell lung cancer (SCLC). Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the presynaptic part of the neuromuscular junction. Its classical clinical triad is proximal muscle weakness, areflexia and autonomic dysfunction. Fifty to sixty percent of LEMS patients have a neoplasia, usually SCLC. The co-occurrence of SCLC and LEMS causes more severe and progressive disease and shorter survival than non-paraneoplastic LEMS. Treatment includes 3,4 diaminopyridine for symptomatic purposes and immunotherapy with prednisolone, azathioprine or intravenous immunoglobulin in patients unresponsive to 3,4 diaminopyridine. Paraneoplastic cerebellar degeneration (PCD) is a syndrome characterized with severe, subacute pancerebellar dysfunction. Serum is positive for VGCC antibody in 41%-44% of patients, usually with the co-occurrence of SCLC. Clinical and electrophysiological features of LEMS are also present in 20%-40% of these patients. Unfortunately, PCD symptoms do not improve with immunotherapy. The role of VGCC antibody in the immunopathogenesis of LEMS is well known whereas its role in PCD is still unclear. All patients presenting with LEMS or PCD must be investigated for SCLC.

Efficacité du rituximab dans un cas de syndrome de Lambert-Eaton non paranéoplasique séronégatif

IntroductionLambert-Eaton myasthenic syndrome is a rare and autoimmune presynaptic disorder of the neuromuscular junction, due in 85% of cases to autoantibodies directed against voltage-gated calcium channels. It is a paraneoplastic disorder in 50 to 60% of cases. Diagnosis involves a proximal muscle weakness and areflexia, associated with a significant increment after post-exercise stimulation in electrophysiological study. Symptomatic treatment is based on 3,4-diaminopyridine. No etiological treatment has proven its efficacy in both paraneoplastic and non-paraneoplastic Lambert-Eaton myasthenic syndrome. Case reportWe report a 41-year-old man who presented with a seronegative non-paraneoplastic Lambert-Eaton myasthenic syndrome in whom conventional immunosuppressive treatments (corticosteroids, azathioprine) failed, and who eventually improved after treatment with rituximab. ConclusionRituximab was an effective and well-tolerated treatment in this case of seronegative non-paraneoplastic Lambert-Eaton myasthenic syndrome. Its indication should be discussed when conventional immunosuppressive therapy fails in both seropositive and seronegative patients.

Lambert-Eaton myasthenic syndrome following H1N1-influenza vaccination - a case report

The outbreak of influenza A (H1N1) pandemic during the year 2009 led to the development of several vaccinations against H1N1 virus. In Finland, 2.6million citizens were vaccinated during pandemic 2009 - 2010 with adjuvanted influenza vaccine, Pandemrix(®) . In this case report, we describe a patient with non-paraneoplastic Lambert-Eaton myasthenic syndrome following Pandemrix(®) vaccination. Development of various autoimmune diseases in genetically predisposed subjects following exposure to certain environmental factors, including vaccinations, is a well-known entity. Clinicians should be aware of the possibility of the induction of autoimmune diseases following vaccinations and actively ask the relevant clinical history in a newly diagnosed patient with an autoimmune disorder.

The pathophysiology and treatment of autoimmune neuromuscular junction diseases

The neuromuscular junction lacks the protection of the blood-nerve barrier and is vulnerable to antibody-mediated disorders. Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies against acetylcholine receptors (AChR) and muscle-specific receptor tyrosine kinase (MuSK)/LDL-receptor related protein 4 which are AChR-associated transmembrane post-synaptic proteins involved in AChR aggregation. The seropositivity rates for AChR positive and MuSK positive MG in Japan are 80-85% and 5-10%/less than 1%,respectively. The incidence of late-onset MG, defined as onset after age 50 years, has been increasing worldwide. A nationwide epidemiological survey in Japan also revealed that the rates of late-onset MG had increased from 20% in 1987 to 42% in 2006. In 2010, a guideline for standard treatments of late-onset MG was published by the Japanese Society of Neurological Therapeutics. Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction and approximately 60% of LEMS patients have a tumor, mostly small cell lung cancer (SCLC), as a paraneoplastic neurological syndrome. The clinical pictures of Japanese LEMS patients are as follows; male dominant sex ratio (3 : 1), mean age 62 years (17-80 years), 61% of LEMS have SCLC, and the remaining are without cancer. In less than 10% of cases there are signs of cerebellar dysfunctions (paraneoplastic cerebellar degeneration with LEMS; PCD-LEMS) as well, often associated with SCLC. Most patients benefit from 3, 4-diaminopyridine plus pyridostigmine. In paraneoplastic LEMS, treatment of the tumor often results in neurological improvement. In non-paraneoplastic LEMS, prednisone alone or combined with immunosuppressants are treatment options. In both MG and LEMS, where weakness is severe, plasma exchange or intravenous immunoglobulin treatment may provide short-term benefit.

Non-paraneoplastic Lambert-Eaton myasthenic syndrome: a brief review of 10 cases

Lambert-Eaton myasthenic syndrome (LEMS) is an immune-mediated disorder of the presynaptic neuromuscular transmission, which more frequently occurs as the remote effect of a neoplasm, in the paraneoplastic form (P-LEMS), or in a non-paraneoplastic form (NP-LEMS); but few studies describe the clinical features of NP-LEMS. We analyzed the clinical manifestations, laboratory findings, electrophysiological studies, and treatment responses in ten Brazilian patients suffering from NP-LEMS. The mean age was 41.5 years. More often neurological findings were hyporeflexia or areflexia with a post-exercise improvement. Treatment response occurred with pyridostigmine, guanidine, prednisone, azathioprine, and cyclosporine; but not response was observed after intravenous immunoglobulin and plasma exchange. Age at onset, clinical manifestations, and electrophysiological abnormalities can help more in the diagnosis than serum antibodies; the symptomatic treatment with pyridostigmine was effective; and the immunosuppressive treatment with prednisone, azathioprine, or cyclosporine was more beneficial than plasma exchange or intravenous immunoglobulin treatment.

Managing non-paraneoplastic Lambert–Eaton myasthenic syndrome: Clinical characteristics in 25 German patients

In about 40% of patients LEMS is not a paraneoplastic phenomenon (NT-LEMS). Several clinical aspects important to these patients remain open, especially the question when a LEMS can definitely be diagnosed as NT-LEMS. Here we describe a series of 25 German NT-LEMS patients regarding their clinical characteristics, duration of symptoms, value of serological markers, paraneoplastic antibodies and FDG-PET/CT. Furthermore, we discuss the current diagnostic criteria of NT-LEMS.

Cerebellar ataxia in non-paraneoplastic Lambert–Eaton myasthenic syndrome

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.

Activité électromyographique neurogène dans un cas de syndrome de Lambert-Eaton non-paranéoplasique

Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of the neuromuscular junction. Electrodiagnosis is characterized by compound muscle action potentials of small amplitude at rest, normalizing immediately after brief exercise or high-rate nerve stimulation. Needle electromyographic (EMG) activity is classically described as normal or myogenic. We report the case of a young patient with a non-paraneoplastic LEMS in whom the initial electroneuromyographic examination showed neurogenic changes in needle EMG concomitant with typical features of presynaptic neuromuscular junction disorder at single and repetitive nerve stimulation. Neurogenic EMG abnormalities were not previously described in patients with LEMS and could result from "functional" reversible denervation, depending on the presence of anti-calcium channel antibodies at axon terminals. Neurogenic features in needle EMG examination in case of subacute motor deficiency should not eliminate the possibility of a presynaptic neuromuscular junction disorder, such as LEMS.

High innate production of interleukin-10 and tumor necrosis factor-α contributes to susceptibility for non-paraneoplastic Lambert–Eaton myasthenic syndrome

Non-paraneoplastic Lambert–Eaton myasthenic syndrome (LEMS) is an antibody-mediated autoimmune disorder, in which genetically determined interleukin-10 (Il-10) and tumor necrosis factor-α (TNF-α) could play a role in the susceptibility for the disease. Therefore, we analyzed the production of Il-10 and TNF-α after whole-blood stimulation in first-degree family members of patients with LEMS without malignancy, as a measure of innate production in the patients. Thirty-six first-degree family members of 10 patients and 80 healthy controls were studied. Both Il-10 ( p=0.037) and TNF-α ( p=0.0016) production were increased in the family members, but had no relation with the severity of LEMS or HLA-B8DR3 carriership. Our findings suggest that high innate production of Il-10 and TNF-α is a susceptibility factor for non-paraneoplastic LEMS.

Lambert-Eaton Myasthenic Syndrome.

Weakness and autonomic dysfunction in Lambert-Eaton myasthenic syndrome (LEMS) can be partially or fully controlled by 3,4-Diaminopyridine. Intravenous immunoglobulin or plasma exchange (PE) plasmapheresis) provides short-term improvement in severely affected patients. In those at risk from paraneoplastic LEMS (cigarette smokers), an intensive search for lung cancer should be undertaken, and specific tumor therapy instituted that likely will improve the neurologic deficit. Prednisolone (1.5 mg per kg of body weight administered on alternate days, maximum dosage is 100 mg) is indicated in those with paraneoplastic or nonparaneoplastic LEMS who fail to respond sufficiently to symptomatic treatment. The addition of azathioprine or cyclosporine is indicated as corticosteroid sparing medications in nonparaneoplastic LEMS. When remission or optimal improvement is judged to be present, prednisolone should be tapered to the minimum dose that effectively controls symptoms. If full withdrawal is achieved, azathioprine dose reduction is similarly initiated. In nonparaneoplastic LEMS patients failing to respond to azathioprine after 1 to 2 years of therapy, physicians should consider substituting cyclosporine.