A 73-year-old woman in complete remission from localized small-cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) 22 years earlier was referred to our hospital and diagnosed with non-small-cell lung cancer. After three courses of pembrolizumab, an immune checkpoint inhibitor, the patient complained of muscle weakness, fatigue, ptosis, and dysarthria. The anti-voltage-gated calcium channel antibody level was elevated, and waxing was observed on a high-frequency repetitive stimulation test using an electromyogram. We diagnosed her with recurrence of LEMS as an immune-related adverse event (irAE) induced by pembrolizumab. After intravenous immunoglobulin therapy, the patient's symptoms improved, and she was discharged.
Carcinoma, Non-Small-Cell Lung , Lambert-Eaton Myasthenic Syndrome , Lung Neoplasms , Small Cell Lung Carcinoma , Female , Humans , Aged , Lung Neoplasms/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/complications , Lambert-Eaton Myasthenic Syndrome/chemically induced , Lambert-Eaton Myasthenic Syndrome/diagnosis , Lambert-Eaton Myasthenic Syndrome/drug therapy , Small Cell Lung Carcinoma/complications
We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Findings from a nerve conduction study and positive findings for anti-P/Q-type voltage-gated calcium channel antibody resulted in a diagnosis of LEMS. This was a rare case of LEMS as a neurological immune-related adverse event induced by atezolizumab therapy.
Lambert-Eaton Myasthenic Syndrome , Lung Neoplasms , Small Cell Lung Carcinoma , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Humans , Lambert-Eaton Myasthenic Syndrome/chemically induced , Lambert-Eaton Myasthenic Syndrome/diagnosis , Lambert-Eaton Myasthenic Syndrome/drug therapy , Lung Neoplasms/complications , Male , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/drug therapy
INTRODUCTION: Myasthenia gravis (MG) Lambert-Eaton (LE) overlap syndrome is a rare condition. Here, we describe the first case of MG-LE overlap syndrome revealed by the anti-programmed cell death 1 inhibitor, nivolumab, in a patient treated for metastatic melanoma. CASE: Three months after receiving nivolumab and 1 month after brain metastasis radiotherapy, our patient developed generalized fatigue with intermittent ptosis and swallowing difficulty suggesting a myasthenic syndrome. Electromyogram findings, anti-acetylcholine receptor, and anti-calcium channel antibodies levels were consistent with an immune-related myasthenic syndrome with specific features for both MG and LE syndromes. Immunotherapy with nivolumab was stopped. Patient was treated with systemic immunosuppressive and anti-cholinesterase drugs, with remarkable improvement of his neurological symptoms. Prolonged partial remission was obtained for his metastatic melanoma without need for a third-line treatment. Two years later, a relapse of hismyasthenic symptoms was observed along with new neurological symptoms related to brain radiation necrosis. CONCLUSION: We describe the first case of MG-LE overlap syndrome diagnosed after anti-PD1 immunotherapy for metastatic melanoma, which appeared after radiation therapy and then relapsed after brain radiation necrosis. We hypothesized a role for brain inflammation as a trigger for MG-LE onset. Neuro-muscular junctions disease induced or revealed by checkpoint inhibitors can be challenging and requires long-term follow-up.
Lambert-Eaton Myasthenic Syndrome , Melanoma , Myasthenia Gravis , Humans , Lambert-Eaton Myasthenic Syndrome/chemically induced , Melanoma/drug therapy , Myasthenia Gravis/chemically induced , Nivolumab/adverse effects , Receptors, Cholinergic
Cerebellar Diseases/chemically induced , Cerebellar Neoplasms/therapy , Immune Checkpoint Inhibitors/adverse effects , Lambert-Eaton Myasthenic Syndrome/chemically induced , Nerve Degeneration/chemically induced , Neuroendocrine Tumors/therapy , Nivolumab/adverse effects , Amifampridine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Calcium Channels, P-Type , Calcium Channels, Q-Type , Cerebellar Diseases/drug therapy , Cerebellar Diseases/immunology , Cerebellar Diseases/physiopathology , Cerebellar Neoplasms/secondary , Female , Glucocorticoids/therapeutic use , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Lambert-Eaton Myasthenic Syndrome/drug therapy , Lambert-Eaton Myasthenic Syndrome/immunology , Lambert-Eaton Myasthenic Syndrome/physiopathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lymph Nodes/diagnostic imaging , Magnetic Resonance Imaging , Middle Aged , Nerve Degeneration/drug therapy , Nerve Degeneration/immunology , Nerve Degeneration/physiopathology , Neuroendocrine Tumors/secondary , Neuromuscular Agents/therapeutic use , Positron Emission Tomography Computed Tomography , Prednisone/therapeutic use , Radiosurgery , Radiotherapy , Rituximab/therapeutic use , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/secondary , Small Cell Lung Carcinoma/therapy , Tomography, X-Ray Computed
BACKGROUND: Alemtuzumab administration is known to cause secondary autoimmune disease but has not been associated with the development of neurologic autoimmune conditions. Lambert-Eaton myasthenic syndrome (LEMS) is caused by autoantibodies directed against calcium channels on the neuromuscular junction. CASE REPORT: We report a case of a patient with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab who develop generalized weakness initially attributed to progression of MS but eventually determined to be due to LEMS. CONCLUSION: Alemtuzumab treatment can result in the development of neurologic autoimmune conditions that could mimic MS progression.
Alemtuzumab/adverse effects , Immunologic Factors/adverse effects , Lambert-Eaton Myasthenic Syndrome/chemically induced , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Humans , Male , Middle Aged
Antirheumatic Agents/adverse effects , Chloroquine/adverse effects , Lambert-Eaton Myasthenic Syndrome/chemically induced , Retinal Diseases/chemically induced , Arthritis, Psoriatic/drug therapy , Electroretinography/drug effects , Female , Humans , Lambert-Eaton Myasthenic Syndrome/diagnosis , Middle Aged , Retinal Diseases/diagnosis , Visual Acuity/drug effects , Visual Field Tests , Visual Fields/drug effects
The possible antigenicity of synaptotagmin, a synaptic vesicle protein acting as a cooperative calcium (Ca2+) receptor in exocytosis, was tested to determine whether it is involved in the induction of Lambert-Eaton myasthenic syndrome in which antibodies against voltage-dependent Ca2+ channels or related molecules play a pathogenic role. Repeated injections to Lewis rats with peptides of synaptotagmin residues 20 through 53 or 1 through 30 that are presumably exposed at the nerve terminal surface during exocytosis induced corresponding antipeptide antibodies; on immunoblots, antibodies recognized synaptotagmin that was expressed in the clonal cells. Electrophysiologically, the peptide (residues 20-53)-immunized rats showed (1) reduced acetylcholine quantal content of end-plate potential, (2) an increase in quantal content at high extracellular Ca2+ concentration, and (3) early facilitation followed by less marked depression of end-plate potential amplitude at a tetanic rate of repetitive nerve stimulation. Findings are similar to those in human Lambert-Eaton myasthenic syndrome and passively transferred Lambert-Eaton myasthenic syndrome in mice, and thus suggest that antibody to a synaptotagmin-voltage-dependent Ca2+ channel complex may be involved in the pathogenesis of Lambert-Eaton myasthenic syndrome. The peptide (residues 1-30)-immunized rats showed no electrophysiological abnormality.
Calcium-Binding Proteins , Lambert-Eaton Myasthenic Syndrome/chemically induced , Lambert-Eaton Myasthenic Syndrome/immunology , Membrane Glycoproteins/immunology , Nerve Tissue Proteins/immunology , Amino Acid Sequence , Analysis of Variance , Animals , CHO Cells , Cricetinae , Cricetulus , Disease Models, Animal , Female , Immunization , Lambert-Eaton Myasthenic Syndrome/physiopathology , Microelectrodes , Molecular Sequence Data , Neuromuscular Junction/physiopathology , Rats , Rats, Inbred Lew , Synaptic Transmission/physiology , Synaptotagmins
Botulinum Toxins/adverse effects , Lambert-Eaton Myasthenic Syndrome/chemically induced , Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Botulinum Toxins/administration & dosage , Electromyography , Female , Humans , Injections , Lambert-Eaton Myasthenic Syndrome/complications , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Middle Aged
A 59 year old man with ischaemic heart disease, developed the clinical and electromyographic changes of the Lambert-Eaton myasthenic syndrome after taking calcium antagonist, diltiazem. The symptoms appeared periodically with a rise and fall in serum level of diltiazem. Extensive search was made for systemic neoplasms and autoimmune diseases without success. Serum antibody to voltage operated calcium channel was not detected.
Autoantibodies/analysis , Calcium Channels/immunology , Coronary Disease/drug therapy , Diltiazem/adverse effects , Lambert-Eaton Myasthenic Syndrome/chemically induced , Calcium Channels/drug effects , Diagnosis, Differential , Diltiazem/therapeutic use , Electromyography/drug effects , Humans , Lambert-Eaton Myasthenic Syndrome/diagnosis , Male , Middle Aged , Neurologic Examination/drug effects