Eaton Myasthenic Syndrome Research Articles

Pulmonary adenocarcinoma presented with Lambert- Eaton myasthenic syndrome

Pulmonary adenocarcinoma presented with Lambert- Eaton myasthenic syndrome

Profile of aminopyridines for Lambert–Eaton myasthenic syndrome

Profile of aminopyridines for Lambert–Eaton myasthenic syndrome Paul Maddison,1 Michael J Keogh,2 Saam Sedehizadeh11Department of Clinical Neurology, Queen's Medical Centre, Nottingham, UK; 2Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Newcastle upon Tyne, UKAbstract: 3,4-diaminopyridine (3,4-DAP) is an effective, symptomatic treatment for Lambert–Eaton myasthenic syndrome (LEMS). Several trials have studied the effects of 3,4-DAP in small numbers of LEMS patients. We systematically reviewed all randomized trials of 3,4-DAP in LEMS to determine the efficacy of this treatment using meta-analysis of clinical and electrophysiological end points. Data from four randomized, placebo-controlled trials revealed that muscle-strength scores increased significantly with 3,4-DAP. Limited meta-analysis performed on two trials using the quantitative myasthenia gravis score indicated that the clinical benefits seen were modest, with an improvement in quantitative myasthenia gravis score of 2.44 points (95% confidence interval: 1.2–3.6). Meta-analysis of the mean change in compound muscle action potential amplitude following 3,4-DAP treatment revealed a significant improvement compared to placebo (1.36 mV, 95% confidence interval: 0.99–1.72). 3,4-DAP is an effective, safe, first-line symptomatic treatment for LEMS, with significant clinical and electrophysiological benefits demonstrated by meta-analysis.Keywords: Lambert–Eaton myasthenic syndrome, 3,4-diaminopyridine, meta-analysis

The association between Lambert–Eaton myasthenic syndrome and small cell lung carcinoma

Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune disorder mediated by autoantibodies to voltage-gated calcium channels. The disorder is diagnosed clinically on the basis of a triad of symptoms (proximal muscle weakness, hyporeflexia, and autonomic disturbance), supported by electrophysiological findings and the presence of autoantibodies. Between 40% and 62% of patients diagnosed with LEMS are found to have small-cell lung cancer (SCLC), almost all of whom develop neurological symptoms before their cancer is diagnosed. Prompt identification of LEMS and appropriate screening for SCLC is key to improving the outcome of both conditions. Here we review the pathophysiology and clinical management of LEMS, focusing particularly on the relationship with SCLC.

Unmasking of incipient amyotrophic lateral sclerosis by botulinum toxin therapy

A 65 year old female was treated with Onyx embolisation of a superior cerebellar aneurysm for subarachnoid haemorrhage, resulting in mild residual left leg spasticity, but independent mobility. Eight years later, her left ankle started to turn inwards, and gradually the foot became inverted, ultimately becoming fixed due to tendon shortening from spasticity. There was no fluctuation in the position of the foot and it could not be easily corrected with passive stretching, as might be expected in dystonia. Examination revealed weakness of left ankle dorsiflexion, with normal sensation, reflexes and a flexor plantar response. MRI/MRA of the brain showed a treated aneurysm with no evidence of recurrence. Her weakness continued to progress and over the next 6 months she went on to develop brisk left knee and ankle jerks and a left extensor plantar response. Though there was no clinical evidence of wasting or fasciculation, an EMG of the left lower limb showed active denervation. A diagnosis of ALS was suspected, but with changes only confined to one limb there was insufficient evidence for an unequivocal diagnosis. In an attempt to alleviate severe pain associated with fixed flexion deformity, she was treated with 1,000 units of botulinum toxin A (Dysport) into the left plantar flexor muscles. Four days later, she rapidly deteriorated, developing generalised limb weakness with loss of ambulation, dysphagia and dysarthria. Her clinical course over the next year was entirely consistent with ALS, involving progressive weakness of all four limbs and respiratory failure, and ultimately requiring hospice care. In ALS a pre-clinical phase of motor neuron degeneration is likely to occur before motor symptoms develop. Botulinum toxin prevents acetylcholine-containing vesicles from binding to the pre-synaptic membrane. In its use in the treatment of sialorrhoea in ALS, there are no published reports of generalised exacerbation of limb muscle weakness. Anecdotal side effects include bilateral temporomandibular joint subluxation [1] and facial weakness [2]. In one case a woman with ALS who received botulinum toxin for sialorrhoea became anarthric and aphagic [3]. Botulinum toxin injection has also unmasked Lambert– Eaton myasthenic syndrome [4] and caused clinical deterioration in myasthenis gravis [5] and mitochondrial cytopathies [6]. The fact that symptoms were remote to the treatment site suggests a systemic effect of the toxin, a well-recognised phenomenon that has been demonstrated electrophysiologically in patients without clinical weakness [7]. Denervation and incomplete re-innervation in ALS may predispose to decompensation of the neuromuscular junction even with small amounts of toxin. It is perhaps surprising that more frequent side effects have not been reported in ALS, and the clinical course in this case may relate to the fact that this patient was treated for spasticity with a much larger dose than that generally used for sialorrhoea [8]. Clinicians should be aware of this potentially serious complication of the use of high-dose botulinum toxin in ALS. L. Kent P. Davies R. Kennett S. Wimalaratna R. Kerr M. R. Turner K. Talbot (&) Department of Neurology, John Radcliffe Hospital, Oxford, UK e-mail: Kevin.talbot@ndcn.ox.ac.uk

Update on treatment options for Lambert–Eaton myasthenic syndrome: focus on use of amifampridine

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

Literature review of the usefulness of repetitive nerve stimulation and single fiber EMG in the electrodiagnostic evaluation of patients with suspected myasthenia gravis or Lambert‐Eaton myasthenic syndrome

A retrospective literature review of the electrodiagnosis of myasthenia gravis (MG) and Lambert--Eaton myasthenic syndrome (LEMS) through July 1998 was performed for the purpose of generating evidence-based practice parameters. There were 545 articles identified, of which 13 articles met at least three of the six criteria set previously by the American Association of Electrodiagnostic Medicine (AAEM). An additional 21 articles were identified from review articles or the references of these first 13 articles leading to a total of 34 articles. Results of studies utilizing repetitive nerve stimulation (RNS) showed that a 10% decrement in amplitude from the first to fourth or fifth intravolley waveform while stimulating at 2--5 HZ is valid for the diagnosis of MG. The degree of increment needed for the diagnosis of LEMS is at least 25% but most accurate when greater than 100%. Abnormal jitter or impulse blocking are the appropriate criteria for diagnosis of neuromuscular junction (NMJ) disorders when using single fiber electromyography (SFEMG). SFEMG is more sensitive than RNS for the diagnosis of disorders of neuromuscular transmission, but may be less specific and may not be available. Therefore, RNS remains the preferred initial test for MG and LEMS.