Lambert Eaton myasthenic syndrome

Other Names: LEMS; Eaton Lambert syndrome; Lambert Eaton syndrome; Myasthenic syndrome of Lambert-Eaton; Myasthenic-Myopathic syndrome of Lambert-Eaton Lambert Eaton myasthenic syndrome (LEMS) is a disorder of the neuromuscular junction. The neuromuscular junction is the site where nerve cells meet muscle cells and help activate the muscles. This syndrome occurs when antibodies interfere with electrical impulses between the nerve and muscle cells. It may be associated with other autoimmune diseases, or more commonly coincide with or precede a diagnosis of cancer such as small cell lung cancer.

Cause

LEMS is a disorder of the immune system, also known as an autoimmune disorder. Autoimmune disorders occur when the body's defense system against foreign organisms (antibodies) attack healthy tissue. LEMS occurs when part of the neuromuscular junction is damaged. The neuromuscular junction is the area between a nerve cell and a muscle cell, where communication occurs through the release of a chemical signal, called acetylcholine (ACh). This results in muscle contraction or movement. When individuals have LEMS, this process is blocked and ACh is not effectively released from nerve cells. In instances where LEMS is associated with cancer, the cause may be related to the body’s attempt to fight the cancer and accidental attack of nerve fiber endings, especially the voltage-gated calcium channels found there. The trigger for the cases not associated with cancer is unknown.

Symptoms

The signs and symptoms of LEMS usually appear around 40 years of age and are characterized by muscle weakness, dysautonomia (autonomic nervous system disorders), and decreased tendon reflexes.

• Muscle weakness may vary in severity and can lead to:
• Difficulty climbing stairs
• Difficulty lifting objects
• Need to use hands to arise from sitting or lying positions
• Difficulty talking
• Difficulty chewing
• Drooping head
• Swallowing difficulty, gagging, or choking
• Vision issues may additionally occur including:
• Blurry vision(Double vision)
• Difficulty maintaining a steady gaze

Other symptoms may include blood pressure changes, dizziness upon rising, and dry mouth.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Calcium channel antibody positivity
• EMG: decremental response of compound muscle action potential to repetitive nerve stimulation.
• EMG: repetitive nerve stimulation abnormality
• Progressive proximal muscle weakness
• Reduced tendon reflexes
• Xerostomia(Dry mouth)

30%-79% of people have these symptoms

• Bulbar signs
• Constipation
• Impotence(Difficulty getting a full erection)
• Small cell lung carcinoma

5%-29% of people have these symptoms

• Hypohidrosis(Decreased ability to sweat)
• Keratoconjunctivitis sicca(Dry eyes)
• Orthostatic hypotension due to autonomic dysfunction

Diagnosis

The diagnosis of Lambert-Eaton myasthenic syndrome can be confirmed by the presence of P/Q-type VGCC along with electrodiagnostic studies.

Serology Antibodies against the P/Q-type VGCC detected in a radioimmunoassay are present in approximately 85% to 95% of patients with Lambert-Eaton myasthenic syndrome.

Electrodiagnostic Testing The diagnosis is usually made with nerve conduction study (NCS) and electromyography (EMG), which is one of the standard tests in the investigation of otherwise unexplained muscle weakness. EMG involves the insertion of small needles into the muscles. NCS involves administering small electrical impulses to the nerves, on the surface of the skin, and measuring the electrical response of the muscle in question. NCS investigation in LEMS primarily involves evaluation of compound motor action potentials (CMAPs) of effected muscles and sometimes EMG single-fiber examination can be used. The initial findings on electrodiagnostic testing described by Eaton and Lambert were a low CMAP (compound muscle action potential) amplitude at rest, a decremental response at low rates of repetitive nerve stimulation (RNS), and an incremental response at high-rate stimulation.

Due to the strong affiliation with malignancy, the diagnosis of Lambert-Eaton myasthenic syndrome should prompt an immediate and extensive search for underlying malignancy. A CT or MRI of the chest is the initial recommended imaging study. PET scan is also used for initial screening if CT is negative.

Blood tests may be performed to exclude other causes of muscle disease (elevated creatine kinase may indicate a myositis, and abnormal thyroid function tests may indicate thyrotoxic myopathy). Antibodies against voltage-gated calcium channels can be identified in 85% of people with EMG-confirmed LEMS.

Treatment

There is no cure for LEMS. Treatment may vary depending on the individual's age, general health, and whether there is an associated cancer or autoimmune disorder. If cancer or an underlying autoimmune disorder is present, treatment should focus on these conditions first. They may result in symptom relief. Medications and therapies that may be used to treat Lambert-Eaton myasthenic syndrome include: 3,4-diaminopyridine (enhances acetylcholine release), anticholinesterase agents (e.g., Pyridostigmine), plasma exchange (where blood plasma is removed and replaced with fluid, protein, or donated plasma), intravenous immunoglobulins (IVIG), and medications that suppress the immune system (e.g., prednisone, azathioprine). The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Amifampridine phosphate (Brand name: Firdapse)amifampridine phosphate (Fridapse) was approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults.

Prognosis

The prognosis for individuals with LEMS varies and is largely dependent on whether there is an underlying cancer or autoimmune disease. The symptoms of LEMS may improve with treatment; however, not all people respond well to treatment and in most instances, symptoms continue to progress over time.