The lambert-eaton myasthenic syndrome

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction. The main symptom in LEMS is proximal muscle weakness in the legs, which is the presenting symptom in most patients. Autonomic dysfunction is also part of the clinical spectrum. Neurological examination generally reveals low or absent tendon reflexes. The muscle weakness and autonomic dysfunction are caused by pathogenic autoantibodies directed against voltage-gated calcium channels (VGCC) present on the presynaptic nerve terminal, causing a decreased release of acetylcholine from nerve terminals. Half of the patients have an associated tumour, usually a small cell lung carcinoma, which expresses VGCC on its surface. If the diagnosis of LEMS is suspected from the distinctive clinical features, confirmation of the diagnosis depends on detection of VGCC autoantibodies or characteristic electrodiagnostic findings. Treatment of LEMS is based on drugs which act at the neuromuscular synapse by increasing either the release or the concentration of acetylcholine, drugs which suppress the immune response or treatment of the underlying tumour.</p

Screening for small-cell lung cancer:A follow-up study of patients with Lambert-Eaton myasthenic syndrome

Purpose: A small-cell lung carcinoma (SCLC) Is found In 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS). We evaluated screening to optimize screening strategy for SCLC. It is important to detect these tumors early in newly diagnosed patients with LEMS to offer optimal patient treatment. Patients and Methods: A large nationwide cohort study of consecutive patients in the Netherlands, seen between 1990 and 2007, were screened for the presence of a tumor using chest x-ray, computed tomography of the thorax (CT-thorax), [ 18F]fluorodeoxyglucose positron emission tomography (FDG-PET), bronchoscopy, and/or mediastinoscopy. Results: SCLC was found in 54 patients, and in 46 patients, no tumor was found during a median follow-up of 8 years (range, 3 to 26 years). All patients with SCLC had a positive smoking history and 86% were still smoking at diagnosis. SCLC was found in 92% of these patients within 3 months and in 96% within a year. At first screening, CT-thorax detected an SCLC in 45 patients (83%), whereas chest x-ray found the tumor in only 23 patients (51%). An SCLC was found during secondary screening in another nine patients (median, 3 months; range, 1 to 41 months). In six patients, a lung tumor was found by CT-thorax or FDG-PET, and in three patients, extrapulmonary metastases were found, initially without identifiable tumor mass on CT-thorax. Conclusion: In almost all patients (96%), the SCLC was found within 1 year of diagnosis. CT-thorax scans detected most of the tumors (93%) and was far more sensitive than chest x-ray (51 %). FDG-PET may have additive value in selected cases. We propose a screening protocol based on CT-thorax and FDG-PET.</p

Screening for small-cell lung cancer:A follow-up study of patients with Lambert-Eaton myasthenic syndrome

Purpose: A small-cell lung carcinoma (SCLC) Is found In 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS). We evaluated screening to optimize screening strategy for SCLC. It is important to detect these tumors early in newly diagnosed patients with LEMS to offer optimal patient treatment. Patients and Methods: A large nationwide cohort study of consecutive patients in the Netherlands, seen between 1990 and 2007, were screened for the presence of a tumor using chest x-ray, computed tomography of the thorax (CT-thorax), [ 18F]fluorodeoxyglucose positron emission tomography (FDG-PET), bronchoscopy, and/or mediastinoscopy. Results: SCLC was found in 54 patients, and in 46 patients, no tumor was found during a median follow-up of 8 years (range, 3 to 26 years). All patients with SCLC had a positive smoking history and 86% were still smoking at diagnosis. SCLC was found in 92% of these patients within 3 months and in 96% within a year. At first screening, CT-thorax detected an SCLC in 45 patients (83%), whereas chest x-ray found the tumor in only 23 patients (51%). An SCLC was found during secondary screening in another nine patients (median, 3 months; range, 1 to 41 months). In six patients, a lung tumor was found by CT-thorax or FDG-PET, and in three patients, extrapulmonary metastases were found, initially without identifiable tumor mass on CT-thorax. Conclusion: In almost all patients (96%), the SCLC was found within 1 year of diagnosis. CT-thorax scans detected most of the tumors (93%) and was far more sensitive than chest x-ray (51 %). FDG-PET may have additive value in selected cases. We propose a screening protocol based on CT-thorax and FDG-PET.</p

Screening for tumours in paraneoplastic syndromes

Objectives: An overview of the screening of tumours related to classical PNS is given. Small cell lung cancer, thymoma, breast cancer, ovarian carcinoma and teratoma, and testicular tumours are described in relation to paraneoplastic limbic encephalitis, subacute sensory neuronopathy, subacute autonomic neuropathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome, myasthenia gravis and paraneoplastic peripheral nerve hyperexcitability.Methods: Many studies with class IV evidence were available; one study reached level III evidence. No evidence-based recommendations for Levels A–C were possible, but good practice points were agreed by consensus.Recommendations: The nature of the antibody, and to a lesser extent the clinical syndrome, determines the risk and type of an underlying malignancy. For screening of the thoracic region a CT thorax is recommended, which if negative is followed by FDG-PET. Breast cancer is screened for by mammography, followed by MRI. For the pelvic region ultrasound is the investigation of first choice followed by CT. Dermatomyositis patients should have CT thorax/abdomen, ultrasound (US) of the pelvic region and mammography in women, US of testes in men under 50 years and colonoscopy in men and women over 50. If primary screening is negative, repeat screening after 3–6 months and screen every 6 months for up to 4 years. In LEMS, screening for 2 years is sufficient. In syndromes where only a subgroup of patients has a malignancy, tumour markers have additional value to predict a probable malignancy

Screening for tumours in paraneoplastic syndromes

Objectives: An overview of the screening of tumours related to classical PNS is given. Small cell lung cancer, thymoma, breast cancer, ovarian carcinoma and teratoma, and testicular tumours are described in relation to paraneoplastic limbic encephalitis, subacute sensory neuronopathy, subacute autonomic neuropathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome, myasthenia gravis and paraneoplastic peripheral nerve hyperexcitability.Methods: Many studies with class IV evidence were available; one study reached level III evidence. No evidence-based recommendations for Levels A–C were possible, but good practice points were agreed by consensus.Recommendations: The nature of the antibody, and to a lesser extent the clinical syndrome, determines the risk and type of an underlying malignancy. For screening of the thoracic region a CT thorax is recommended, which if negative is followed by FDG-PET. Breast cancer is screened for by mammography, followed by MRI. For the pelvic region ultrasound is the investigation of first choice followed by CT. Dermatomyositis patients should have CT thorax/abdomen, ultrasound (US) of the pelvic region and mammography in women, US of testes in men under 50 years and colonoscopy in men and women over 50. If primary screening is negative, repeat screening after 3–6 months and screen every 6 months for up to 4 years. In LEMS, screening for 2 years is sufficient. In syndromes where only a subgroup of patients has a malignancy, tumour markers have additional value to predict a probable malignancy

Data from: Long‐term follow‐up, quality of life and survival of Lambert‐Eaton myasthenic syndrome patients

Objective To study survival and characterize long-term functional impairments as well as health-related quality of life (HRQOL) of Lambert-Eaton myasthenic syndrome (LEMS) patients. Methods In this observational study, survival of LEMS patients, separately for non-tumor (NT) and small-cell lung cancer (SCLC), was compared to the Dutch general population and to patients with SCLC. Disease course in LEMS patients was recorded retrospectively. Several scales for functional impairments and health-related quality of life were assessed. Results We included 150 LEMS patients. Survival was similar to the general population in 65 NT-LEMS patients. Tumor survival was significantly longer in 81 SCLC-LEMS patients compared to non-LEMS SCLC patients (overall median survival 17 vs. 7.0 months,

Data from: Long‐term follow‐up, quality of life and survival of Lambert‐Eaton myasthenic syndrome patients

Objective To study survival and characterize long-term functional impairments as well as health-related quality of life (HRQOL) of Lambert-Eaton myasthenic syndrome (LEMS) patients. Methods In this observational study, survival of LEMS patients, separately for non-tumor (NT) and small-cell lung cancer (SCLC), was compared to the Dutch general population and to patients with SCLC. Disease course in LEMS patients was recorded retrospectively. Several scales for functional impairments and health-related quality of life were assessed. Results We included 150 LEMS patients. Survival was similar to the general population in 65 NT-LEMS patients. Tumor survival was significantly longer in 81 SCLC-LEMS patients compared to non-LEMS SCLC patients (overall median survival 17 vs. 7.0 months, p&lt;0.0001). At diagnosis, 39 patients (62%) of 63 patients with complete follow-up data were independent for ADL activities, improving to 85% at 1-year follow-up. Physical HRQOL composite score (55.9) was significantly lower than in the general population (76.3, p&lt;0.0001) and comparable to myasthenia gravis (60.5) Mental HRQOL composite score was 71.8 in LEMS patients, comparable to the general population (77.9, p=0.19) and myasthenia gravis (70.3). Conclusions This study shows NT-LEMS patients have normal survival. SCLC-LEMS patients have an improved tumor survival, even after correcting for tumor stage. A majority of LEMS patients report a stable disease course and remain or become independent for self-care after treatment