Lambert-Eaton Syndrome

Part of the Current Clinical Neurology book series (CCNEU)


The Lambert-Eaton syndrome (LES) is an autoimmune presynaptic disorder of peripheral cholinergic neurotransmission characterized by proximal weakness and autonomic dysfunction. Approximately 60% of cases are associated with small-cell lung carcinoma (SCLC), which can appear before or after the clinical manifestations of LES. The P-/Q-type voltage-gated calcium channel in motor nerve terminals, classified by structure and function as Cav2.1, is the presumptive target of antibodies that cause LES. Antigenically similar calcium channels are expressed in the surface membranes of SCLC tumor cells. When neuronal Cav2.1 channels are functionally impaired, nerve-stimulated quantal release of the neurotransmitter acetylcholine (ACh) is reduced. This lowers the safety margin for synaptic transmission at the neuromuscular junction and in certain autonomic nerve terminals, leading to weakness at rest that is temporarily improved by exertion, as well as xerostomia, impotence, and hypohidrosis. The diagnosis of LES is based on clinical manifestations, abnormalities on nerve conduction studies and EMG, and serological testing. Weakness predominately affects hip flexor muscles but can be generalized. Nerve conduction studies classically demonstrate low-amplitude compound muscle action potentials at rest with facilitation induced by exercise or by high-frequency repetitive stimulation. Needle EMG testing typically demonstrates small varying motor unit potentials without fibrillations. P-/Q-type voltage-gated calcium channel antibodies are detected in serum in more than 90% of LES patients. Treatment of weakness is symptomatic, with agents that improve the safety margin of neuromuscular transmission (e.g., 3,4-diaminopyridine in combination with pyridostigmine) and immunosuppressant therapy, and is cancer-directed in paraneoplastic cases.


Paraneoplastic syndrome Small-cell lung cancer P-/Q-type voltage-gated calcium channels (Cav2.1) Autoimmune neuromuscular disease 3,4-diaminopyridine Dysautonomia 


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Clinical Neurophysiology and Neuromuscular Disease, Department of NeurologyMayo ClinicRochesterUSA
  2. 2.Departments of Neurology and Laboratory Medicine and Pathology, Divisions of Clinical Neurophysiology and Neuromuscular Disease, and Neuroimmunology LaboratoryMayo ClinicRochesterUSA

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