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Annals of Palliative Medicine Oct 2016Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon autoimmune idiopathic or paraneoplastic syndrome producing antibodies against voltage presynaptic calcium...
Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon autoimmune idiopathic or paraneoplastic syndrome producing antibodies against voltage presynaptic calcium channels. According to previous studies, many patients with LEMS experience remission in both the clinical symptoms of muscle weakness and the electrophysiologic abnormalities after successful treatment of lung SCC. However, some patients might not respond to conventional therapy and eventually require palliative care. Hereby, we reported a LEMS patient with advanced lung malignancy was referred for palliative care. He was benefited from multidisciplinary approach even with limited survival. In this case, use of 3,4-diaminopyridine (3,4-DAP) had other roles apart from symptomatic treatment.
Topics: 4-Aminopyridine; Action Potentials; Amifampridine; Female; Humans; Lambert-Eaton Myasthenic Syndrome; Male; Middle Aged; Neural Conduction; Palliative Care; Potassium Channel Blockers; Terminally Ill; Tomography, X-Ray Computed
PubMed: 27506750
DOI: 10.21037/apm.2016.06.01 -
Journal of Medical Case Reports Mar 2015Lambert-Eaton myasthenic syndrome is a rare autoimmune disorder of neuromuscular transmission due to the presence of antibodies to presynaptic P/Q-type voltage-gated...
INTRODUCTION
Lambert-Eaton myasthenic syndrome is a rare autoimmune disorder of neuromuscular transmission due to the presence of antibodies to presynaptic P/Q-type voltage-gated calcium channels. The gold standard of therapy is the potassium channel blocker 3,4-diaminopyridine. To the best of our knowledge, no clinical reports have been published to date about long-term follow-up outcomes in patients who discontinued 3,4-diaminopyridine therapy. In addition, we know of no recent articles in which the natural history in patients with autoimmune-mediated Lambert-Eaton myasthenic syndrome has been addressed. In this report, we describe the cases of two such patients.
CASE PRESENTATION
Patient 1 was a Caucasian man who had been diagnosed at age 15 years with Lambert-Eaton myasthenic syndrome with symptoms of fluctuating muscle weakness and easy fatigability. These symptoms stabilized, and his electrophysiological parameters normalized, during treatment with a maintenance dose of 50mg/day of 3,4-diaminopyridine. After 5.5 years, however, he wished to discontinue the treatment. After that point, his electrophysiological parameters and presynaptic P/Q-type voltage-gated calcium-channel antibody titer remained stable. During the 15-year follow-up period, patient 1 reported mild exertion-induced complaints but did not feel restricted in his occupation and most daily activities. Patient 2 was a Caucasian man diagnosed at 32 years of age with a moderate limb girdle syndrome. He was treated with up to 80 mg/day of 3,4-diaminopyridine. Because of the drug's very short-lasting effect (<1 hour), however, he took it mostly irregularly (≤ 1 × 20 mg/day). During the 14- year period of observation, his repetitive nerve stimulation responses and presynaptic P/Q-type voltage-gated calcium-channel antibody titer remained stable, his compound muscle action potential amplitudes were decreasing and his clinical symptoms did not deteriorate. At his last follow-up examination, patient 2 was independent in all of his daily activities.
CONCLUSION
Some patients with autoimmune-mediated Lambert-Eaton myasthenic syndrome show a stable clinical long-term course without treatment. The benefit of each long-term therapy should be critically assessed during follow-up, and possible side effects should be balanced against the quality of life in these patients.
Topics: 4-Aminopyridine; Adult; Amifampridine; Calcium Channels; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Lambert-Eaton Myasthenic Syndrome; Male; Middle Aged; Potassium Channel Blockers
PubMed: 25885033
DOI: 10.1186/s13256-015-0524-9 -
ACS Chemical Neuroscience Aug 2014Botulinum neurotoxicity is characterized by peripheral neuromuscular blockade/flaccid paralysis that can lead to respiratory failure and ultimately death. Current...
Botulinum neurotoxicity is characterized by peripheral neuromuscular blockade/flaccid paralysis that can lead to respiratory failure and ultimately death. Current therapeutic options provide relief in a pre-exposure scenario, but there are no clinically approved postexposure medical countermeasures. Here, we introduce a platform that utilizes a combination of a toxin sequestering agent and a pharmacological antagonist to ablate botulinum neurotoxicity in a well-defined mouse lethality assay. The platform was constructed to allow for ready exchange of sequestering agent and/or pharmacological antagonist for therapeutic optimization. As such, we attempted to improve upon the pharmacological antagonist, a potassium channel blocker, 3,4-diaminopyridine, through a prodrug approach; thus, a complete kinetic decomposition pathway is described. These experiments provide the first proof-of-principle that a synergistic combination strategy can be used to reduce toxin burden in the peripheral using a sequestering antibody, while restoring muscle action via a pharmacological small molecule antagonist.
Topics: 4-Aminopyridine; Amifampridine; Animals; Botulinum Antitoxin; Botulinum Toxins; Drug Therapy, Combination; Female; Kinetics; Mice; Neurotoxicity Syndromes; Potassium Channel Blockers; Sequestering Agents; Survival Analysis
PubMed: 25000171
DOI: 10.1021/cn500135h