Update on treatment options for Lambert–Eaton myasthenic syndrome: focus on use of amifampridineLambert-Eaton Myasthenic Syndrome Causes, Symptoms and Treatment and Related Disorders

Update on treatment options for Lambert–Eaton myasthenic syndrome: focus on use of amifampridine.
 Published online 2011 May 30 

Abstract

The mainstay of treatment for LEMS is symptomatic but immunotherapy is needed in more severely affected patients. 3, thereby prolonging the action potential and increasing presynaptic calcium concentrations 4-DAP blocks presynaptic potassium channels. 4-DAP for increasing muscle strength and resting compound muscle action potentials has been demonstrated by four placebo-controlled trials the efficacy of 3. More than half of the affected patients have associated small cell lung cancer, and thorough screening for an underlying malignancy is crucial. 4-diaminopyridine (3, amifampridine) has been shown to be more effective 4-DAP, 3, while acetylcholinesterase inhibitors were the first drugs to be used for the amelioration of symptoms. The most common serious adverse events are epileptic seizures. 3, 4-DAP is currently the treatment of choice in patients with Lambert–Eaton myasthenic syndrome Antibodies against presynaptic voltage-gated calcium channels reduce the quantal release of acetylcholine, in Lambert–Eaton myasthenic syndrome (LEMS), causing muscle weakness and autonomic dysfunction. Side effects are usually mild, and the most frequently reported are paresthesias. This then results in increased quantal release of acetylcholine. Symptomatic therapies aim at increasing the concentration of acetylcholine at the muscle endplate.

The CMAP shows a decrement at low stimulation frequency. Resulting in the characteristic increment calcium is thought to accumulate in the nerve ending and facilitate acetylcholine release, at high stimulation frequency, in contrast. 12 Heart rate variability as a measure of parasympathetic innervation of the heart is more often affected than orthostatic regulation, which is a function of the sympathetic nervous system 11. Development of multiple clinical symptoms within the first 6 months, the presence of cerebellar symptoms, a history of smoking, presence of Sox1 antibodies, older age, and absence of human leucocyte antigen B8 all increase the likelihood of associated small cell lung cancer. 11 Sensorimotor neuropathy is not associated with autonomic symptoms in LEMS patients. Characterized by proximal muscle weakness, and posttetanic potentiation in addition to autonomic dysfunction an antibody-mediated syndrome

Lambert–Eaton myasthenic syndrome (LEMS) is a disorder of the neuromuscular junction, depressed tendon reflexes. 12 Autoantibodies against voltage-gated calcium channels are also thought to underlie the autonomic dysfunction, although this view is not unchallenged. Constipation or impaired bowel control, and bladder dysfunction are also found frequently alterations in sudomotor function, dry eyes. 10 Reduced acetylcholine release at the neuromuscular endplate results in decreased frequency of miniature endplate potentials of normal amplitude. The acetylcholine released is not suf-ficient to activate most of the postsynaptic muscle fibers, following a single nerve impulse, therefore the compound muscle action potential (CMAP) is reduced. Lowering the amount of presynaptic calcium and thus reducing the quantal release of acetylcholine 7, 8 These pathogenic antibodies cause a downregulation of voltage-gated calcium channels. Either due to an immune-mediated effect or due to earlier diagnosis and treatment of the cancer 15 The presence of LEMS appears to improve survival in patients with small cell lung cancer. Small cell lung cancer is usually identified within 2 years of the diagnosis of LEMS Other antibody targets, have been discussed namely synaptotagmin and presynaptic M1 muscarinic acetylcholine receptors, 9 For 10%–15% of voltage-gated calcium channel-antibody negative LEMS patients. 1, 11

LEMS is associated with small cell lung cancer in 50%–60% of patients, 13 who show more rapidly progressive LEMS. 14 Recently, the Dutch-English LEMS Tumor Association Prediction (DELTA-P) score has been developed to distinguish more accurately between patients at high risk versus low risk for developing small cell lung cancer. 11 The most commonly reported symptoms are dry mouth and male impotence. Autonomic dysfunction is present in the majority of LEMS patients and is usually mild. A clinical correlate of this phenomenon is seen in improvement of previously absent tendon reflexes following a short period of forceful muscle contraction. 1–3 The clinical response of LEMS patients to plasma exchange4 and successful passive transfer experiments using patients’ immunoglobulin4–6 led to discovery of serum antibodies to P/Q-type voltage-gated calcium channels as the cause of LEMS.

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