Eaton-lambert Syndrome

Patient Education

What is Lambert-Eaton myasthenic syndrome?

It is a disorder of neuromuscular transmission caused by the impaired presynaptic release of acetylcholine (ACh).

What is Pathogenesis of Lambert-Eaton myasthenic syndrome?

Lambert-Eaton myasthenic syndrome (LEMS) results from an autoimmune attack directed against the P/Q subtype of voltage-gated calcium channels (VGCCs) on the presynaptic motor nerve terminal. These channels are also found in high numbers in the tumour cells associated with LEMS (small-cell cancer of the lung). It is thought that antibodies are produced against the tumour VGCCs but are then also responsible for the resulting attack on noncancerous cells and their sequelae.

What are Risk factors for it?

• Cancer - typically small-cell carcinoma of the lung(SCCL) is present when weakness begins, or is later found in approximately 50% of patients. In most cases the cancer is found within 2 years after the onset of Lambert-Eaton myasthenic syndrome (LEMS); within 4 years in virtually all cases.
• Smoking and age at onset are major risk factors for cancer in LEMS. All patients with associated SCCL have a history of long-term smoking. Only half of the patients with autoimmune LEMS are long-term smokers, eg a patient aged <50 years, who does not have cancer discovered in the first 2 years after diagnosis, is unlikely to have an underlying carcinoma. But, a long-term smoker with the onset of LEMS after the age of 50 years, probably has underlying lung cancer.

What are the Symptoms of Lambert-Eaton myasthenic syndrome?

• Symptoms usually begin insidiously, with many patients undiagnosed for months, or years.
• Weakness is a major symptom. Usually, in the proximal muscles of lower limb. Gait is affected.
• Muscles may ache and be tender. Oropharyngeal and ocular muscles are mildly affected.
• Bulbar and respiratory muscles are usually spared.
• Autonomic symptoms - dry mouth, impotence in males, and postural hypotension may be seen Signs.
• Reduced strength in the proximal muscles of the arms and legs, producing a waddling gait and difficulty with raising the arms.
• Eyelid ptosis and mild diplopia is found in 25% of patients.
• Occasionally there may be difficulty in chewing, speech or swallowing.
• Approximately 50% of patients may find strength improves initially on exercise, but then lessens as exercise is sustained.
• Deep tendon reflexes are reduced or absent. Sensory examination is normal unless there is a coincident peripheral neuropathy associated with underlying cancer.

What Investigations my doctor will do?

• The only methods of differentiating myasthenia gravis and Lambert-Eaton myasthenic syndrome (LEMS) are the detection of acetylcholine (ACh) receptor antibodies or discovering the presence of underlying malignancy.
• A serum test for voltage-gated calcium-channel antibodies is now available. Antibodies have been reported in 75-100% of patients with LEMS and underlying cancer, and 90% of patients without. (They are found in <5% of patients with myasthenia gravis and up to 25% in patients with antibody levels secondary to, for example, systemic lupus erythematosus (SLE) or rheumatoid arthritis.)²
• CT or MRI scanning of the chest to exclude chest malignancy.
• ACh receptor antibodies are occasionally found in low titres in patients with LEMS.
• Electrophysiological testing shows a small compound muscle action potential and facilitation with exercise or 20 Hz repetitive stimulation.⁵
• Bronchoscopy may be necessary if imaging studies are normal, but the risk of small-cell carcinoma of the lung (SCCL) is high.

What is treatment for it?

• Several drugs are available for symptomatic treatment, eg guanidine, aminopyridines or acetylcholinesterase inhibitors.⁸ Other therapies aim to deplete the serum autoantibodies or to suppress the immune system.

• The limited evidence from randomised controlled trials (RCTs) shows either 3,4-aminopyridine or intravenous (IV) immunoglobulin (dose 2 g/kg) improves muscle strength. There are insufficient data to quantify the effect.

• Other treatments, eg plasma exchange, steroids and immunosuppressive agents (prednisolone or azathioprine), have not been tested in RCTs.

• Cholinesterase inhibitors: they work by inhibiting the breakdown of ACh. This is intended to help compensate for the relative lack of ACh release in LEMS. They usually do not provide a significant improvement. A few patients with mild disease may notice the benefit.

• In patients who do not have cancer, aggressive immunotherapy is justified.

Prognosis

This depends mainly on the presence and nature of any underlying malignancy or the severity of any associated autoimmune disease.