LambertEatonSyndrom

Lambert-Eaton syndrome, also known as Lambert-Eaton myasthenic syndrome (LEMS), is a rare autoimmune disorder of the neuromuscular junction characterized by proximal muscle weakness and autonomic symptoms. It is commonly associated with an underlying malignancy, most often small cell lung carcinoma, though a non-paraneoplastic form occurs.

The disease results from autoantibodies against presynaptic voltage-gated P/Q-type calcium channels at the motor nerve terminal. This reduces calcium influx and acetylcholine release, leading to a decreased end-plate potential and fatigable weakness. Strength may transiently improve with brief activity due to facilitation of transmitter release.

Clinical features typically include proximal leg-dominant weakness, difficulty rising from a chair or climbing stairs, and fatigability. Autonomic symptoms such as dry mouth, constipation, orthostatic hypotension, and impaired sweating are common. Ocular and bulbar involvement is less frequent and usually milder than in myasthenia gravis. Reflexes are often reduced and may recover somewhat with repeated use.

Diagnosis relies on clinical suspicion supported by objective testing. Nerve conduction studies commonly show reduced compound muscle action potential (CMAP) amplitudes that exhibit a characteristic incremental response after high-frequency stimulation or post-exercise facilitation. Anti-VGCC antibodies may be detected in serum. A search for an underlying tumor is essential, typically with chest imaging and age-appropriate cancer screening.

Treatment focuses on two goals: managing symptoms and treating the underlying cancer if present. Symptomatic therapy includes acetylcholinesterase inhibitors (such as pyridostigmine) and amifampridine to boost acetylcholine release. Immunotherapy with corticosteroids or other immunosuppressants may be used, and rituximab is considered in some cases. Physical therapy supports muscle strength and endurance. Prognosis improves with tumor treatment and appropriate autoimmune management, though cancer status strongly influences overall outcome. Regular follow-up and cancer surveillance are advised.