Lambert–Eaton myasthenic syndrome

The Lambert -Eaton syndrome Rooke, also known as LES, LEMS, Pseudomyasthenie and English. Called Lambert -Eaton ( myasthenic ) syndrome is a rare neurological disorder whose characteristic feature is a proximal muscle weakness stressed. In voluntary movements a maximum force development is reached after a few seconds, which then leads in advanced effort in fatigue of the muscles concerned.

The reason is a disturbed signal transmission between nerve and muscle with a presynaptic defect. The disease is one of the autoimmune diseases. Are formed antibodies against the presynaptic calcium channels. Thus, the neurotransmitter release is hindered, which interferes with the conduction of nerve signals to the muscle cells.

Was named the syndrome after the American doctors Lealdes McKendree Eaton, Edward Howard Lambert and Edward Douglas Rooke. They were the first to comprehensively after diagnosis and electrophysiological studies of this disease reported in 1956.

The LES is, together with myasthenia gravis and congenital myasthenic syndromes myasthenem syndrome to.

The B- lymphocytes of the affected people develop antibodies against the presynaptic calcium channels at the neuromuscular junctions, the switching between nerve and muscle. The antibodies are directed against voltage-dependent calcium channels of the P / Q - type. Thereby, the release of acetylcholine is inhibited and transfer nerve stimuli only weakened from the nerve to the muscle cell; the muscle response is slow. Does the nerve stimulus prolonged period to acetylcholine accumulates in the synaptic cleft and the muscle force increases until the usual measure on ( Lambert characters).

In about 60 % of people with LES there is a malignant tumor that often a small cell lung cancer (SCLC ), and occasionally a prostate cancer, thymoma, or a lymphoproliferative disorder, such as lymphoma. Although the molecular mechanism at the neuromuscular synapse is precisely elucidated, however, the trigger of the LES is not known until today. The LES is one of the paraneoplastic syndromes and can already occur at an early stage, before the tumor is known. Thus, the Lambert -Eaton syndrome may give a first indication of the existence of a lung tumor and the affected people need to be investigated accordingly.

In approximately 40% of patients there is no malignant tumor. This idiopathic form is associated especially in patients under 30 years old often and often with other autoimmune diseases, particularly the systemic lupus erythematosus.

Incidence

The incidence of Lambert-Eaton syndrome is 3.4 per one million people. Men are two to five times more often affected than women. Since women currently suffer increasingly frequent in lung cancer, and the proportion of women increases the Lambert -Eaton syndrome.

Symptoms

Typical is a proximal muscle weakness of the extremities, usually bein stressed. Particularly often the thigh is affected with hip and knee, which mainly manifests itself when climbing stairs. In addition, the core muscles are affected.

Other causes of proximal muscle weakness are the stressed myasthenia gravis and idiopathic inflammatory myopathy ( polymyositis as, dermatomyositis, inclusion body myositis ), which are more common with 150 and 100-200 cases per million. The diagnosis is often difficult, and up to 21% of patients will first receive a misdiagnosis.

In addition to the proximal stressed muscle weakness is groundbreaking that no sensitive problems. Also lacking are the typical for myasthenia gravis paralysis of eye muscles, paralysis of the eyelids (ptosis ) is rare.

On the other hand often occur dry mouth, headache and cognitive disorders on as an indication of involvement of the autonomic nervous system ( in more than 90%) and the central nervous system.

Other symptoms may include:

• Constipation
• Impotence
• Swallowing and speech difficulties (dysarthria )
• Accommodation disturbances ( blurred vision )
• Bladder dysfunction
• Ptosis ( droopy eyelids )
• Hypohidrosis ( decreased sweating )
• Hyporeflexia (weakened tendon reflexes )
• Changes in blood pressure

Diagnosis

If the described symptoms of suspected LES, there is a neurophysiological testing. Here are diminished as an indication of muscle weakness, motor action potential, even in clinically unaffected muscles. In a high -frequency stimulation of peripheral nerves or stimulation by a strong muscular load, the force increases temporarily increased ( Lambert characters ), while in myasthenia gravis fluctuation and an increasingly lower muscle strength ( fatigue ) can be observed. However, the precision and accuracy of the neurophysiological tests are dependent on the experience of the examiner.

Also, a Tensilon be performed. This can be positive, that is, the maximum force is higher than previously by Tensilongabe, as is also the case of myasthenia gravis.

In addition, laboratory tests can the suspicion of a Lambert- Eaton syndrome harden: In approximately 85 % of patients the causative antibodies against voltage-gated calcium channels ( VGCC = voltage gated calcium channel) from the P / Q-type can be detected.

In case of an LES, the European Federation of Neurological Societies recommends that if no malignant tumor is known, a computed tomography ( CT) perform the thorax, and this should be negative, then a positron emission tomography (PET) or perform a PET-CT. 96 % of all malignant tumors are found in the first year after diagnosis of the LES.

Therapy

If a person has the Lambert- Eaton syndrome in terms of a paraneoplastic syndrome, the cancer is treated primarily underlying. Thus, the symptoms of the LES can often improve significantly. For persistent muscle weakness and pyridostigmine, intravenous immunoglobulin or 3,4- diaminopyridine ( Amifampridine ) can be used, but the efficacy of these agents is insufficient evidence in trials.

In idiopathic forms can immunosuppression by glucocorticoids, azathioprine or immunoglobulins reduce the production of autoantibodies, leading to an improvement of symptoms.

Symptomatic treatment can be tackled with the potassium channel blocker Amifampridine. This substance increases by blocking potassium efflux ( iK ) calcium influx ( iCa ) and counters in this way the effect of the antibody; it results in increased Acetylcholinausstrom, the conduction and thus the muscle strength is improved.

In addition, a plasmapheresis to reduce antibody levels and thus improve the symptoms.