Eaton-Lambert syndrome

Diseases selectively targeting spinal cord and brainstem motor neurons (e.g. amyotrophic lateral sclerosis and the familial spinal muscular atrophies) or the presynaptic component of neuromuscular junctions (e.g. Lambert-Eaton syndrome, botulism and Ixodes tick paralysis) cause weakness without sensory impairment. Disorders involving the enteric nervous system (e.g. Chagas disease and Hirschsprung s disease) impair bowel motility. 

Measuring muscle-evoked responses to repetitive motor nerve electrical stimulation permits detection of presyn-aptic neuromuscular junction dysfunction. In botulism and the Lambert-Eaton syndrome, repetitive stimulation elicits a smaller than normal skeletal muscle response at the beginning of the stimulus train, due to impaired initial release of acetylcholine-containing vesicles from presyn-aptic terminals of motor neurons followed by a normal or accentuated incremental muscle response during repeated stimulation. This incremental response to repetitive stimulation in presynaptic neuromuscular disorders can be distinguished from the decremental response that characterizes autoimmune myasthenia gravis, which affects the postsynaptic component of neuromuscular junctions. 

Lambert-Eaton syndrome is an antibody-mediated neuromuscular junction disorder. This disorder, which is most frequently encountered in patients with small-cell lung carcinoma, is characterized clinically by weakness and hyporeflexia. The impaired release of acetylcholine vesicles from presynaptic terminals at neuromuscular junctions that causes the weakness is a consequence of autoantibodies against small cell carcinoma epitopes that cross-react with and downregulate the expression of motor nerve terminal Ca2+ channels [39]. (See in Ch. 43.)... 

Antibodies cause calcium channel dysfunction in Lambert-Eaton syndrome 724... 

Myasthenia gravis Lambert-Eaton syndrome Neuromyotonia (Isaac s syndrome) Intoxications and metabolic diseases... 

Antibodies cause calcium channel dysfunction in Lambert-Eaton syndrome. Some patients with cancer, especially small-cell carcinoma of the lung, develop a syndrome of weakness associated with autonomic dysfunction as part... 

Lindstrom, J. Immunobiology of myasthenia gravis, experimental autoimmune myasthenia gravis, and Lambert-Eaton syndrome. Annu. Rev. Immunol. 3 109-131,1985. 

Neuropathic disorders Administer with caution in individuals with peripheral motor neuropathic diseases (eg, amyotrophic lateral sclerosis, motor neuropathy) or neuromuscular junctional disorders (eg, myasthenia gravis, Lambert-Eaton syndrome). Patients with neuromuscular disorders may be at increased risk of clinically significant P.787... 

Flink MT, Atchison WD (2003) Ca2+ channels as targets of neurological disease Lambert-Eaton Syndrome and other Ca2+ channelopathies. J Bioenerg Biomembr 35 697-718. 

Lennon VA, Kryzer TJ, Griesmann GE, O Suilleabhain PE, Windebank AJ, Woppmann A, Miljanich GP, Lambert EH (1995) Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 332 1467-1474. 

The plant is calledphysostigma venenosum (venenum = lat. poison) A similar disease, called Lambert Eaton syndrome, is caused by anti-... 

Kim Yl, Neher E. IgG from patients with Lambert-Eaton syndrome blocks voltage-dependent calcium channels. Science 1988 239 405-408. 

Separate from myasthenia gravis is the Lambert-Eaton syndrome, where symptoms similar to those in myasthenia gravis occur in association with a carcinoma in 60% of patients this is a small-cell lung cancer. The defect here is presynaptic with a deficiency of acetylcholine release due to an autoantibody directed against L-type voltage-gated calcium channels. 

Patients with the Lambert-Eaton syndrome do not usually respond well to anticholinesterases. The drug 3,4-diaminopyridine (3,4-DAP) increases neurotransmitter release and also the action potential (by blocking potassium conductance) these actions lead to a nonspecific excitatory effect on the cholinergic system, and provide benefit. It should be taken orally, 4-5 times per day. Adverse effects... 

Calcium channel blockers can worsen myasthenic syndromes. Myasthenia gravis can deteriorate with oral verapamil (58). A patient with Lambert-Eaton syndrome and a small-cell carcinoma of the lung developed respiratory failure within hours of starting treatment with verapamil for atrial flutter, and required assisted ventilation (59). Only after verapamil had been withdrawn did breathing improve. Verapamil affects calcium channels in nerve membranes in animals, but the experimental concentrations used exceeded those found in clinical practice (59). Thus, the evidence for a drug-related effect is circumstantial. In another case, diltiazem triggered Lambert-Eaton syndrome, which improved with drug withdrawal (60). 

Krendel DA, Hopkins LC. Adverse effect of verapamil in a patient with the Lambert-Eaton syndrome. Muscle Nerve 1986 9(6) 519-22. 

Intoxication with depressants (e.g., acute ethanol intoxication), organophosphates, carbon monoxide, or nerve gas Lambert-Eaton syndrome... 

Guanidine is a cholinergic muscle stimulant that enhances release of acetylcholine following a nerve impulse and appears to slow rates of depolarization and repolarization of muscle-cell membranes. It is indicated in reducing symptoms of muscle weakness and easy fatigability associated with Lambert-Eaton syndrome. 

The degree of recorded jitter in SFEMG is directly related to the release of ACh and the function of the ACh receptors in the NMJ. SFEMG therefore provides a window into the operation of the NMJ. Jitter is characteristically increased in conditions (both pre- and post-junctional) of the NMJ which reduce the safety margins of neuromuscular transmission. Thus, there is increased jitter in conditions such as myasthenia gravis and Lambert-Eaton syndrome. Jitter is also increased following the administration of small doses... 

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