Lambert-Eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder of paraneoplastic or primary autoimmune etiology.

Epidemiology

LEMS is the second most common neuromuscular junction disease after myasthenia gravis. 

Up to two-thirds of LEMS present as a paraneoplastic syndrome secondary to malignancy, which is nearly always small-cell lung cancer.

Clinical presentation

The most common clinical feature is progressive proximal leg weakness ¹. Deep tendon reflexes are almost always decreased or absent ¹. A less prominent but characteristic feature is autonomic dysfunction, most commonly dry mouth ¹. Less common features include oropharyngeal and ocular symptoms related to weakness, such as dysphagia, dysarthria, ptosis, and diplopia ¹.

The diagnosis is confirmed by electrodiagnostic studies and serology. Specifically, repetitive nerve stimulation demonstrates an increase in compound muscle action potential during high-frequency stimulation or after 10 seconds isometric exercise, a phenomenon known as postactivation facilitation ¹. Antibodies against the P/Q-type voltage-gated calcium channel (anti-VGCC) are relatively specific for the diagnosis ¹.

Radiographic features

A diagnosis of LEMS should prompt a search for an underlying malignancy, at least including chest CT, with additional consideration of FDG-PET ^4,5. These studies most commonly reveal a tumor corresponding to small-cell lung cancer.

Treatment and prognosis

Management includes treatment of the underlying malignancy (if present) and pharmacotherapy. Pharmacotherapy options include amifampridine (3,4-diaminopyridine), pyridostigmine, and in refractory cases, immunosuppression (e.g. combination intravenous immunoglobulin, prednisolone, azathioprine) ⁶.

History and etymology

The syndrome is named after American neurologists Edward Howard Lambert (1915-2003) and Lealdes McKendree Eaton (1905-1958) who first described the condition in a conference presentation of six patients in 1956, with their Canadian colleague Edward Douglas Rooke (1912-2001) ⁷. Lambert and Eaton subsequently published their seminal paper describing the neurophysiological characteristics of the condition in 1957 ^7,8.