Cereda, C.

Kuntzer, T.

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J Neurol (2008) 255:1259–1260DOI 10.1007/s00415-008-0856-0 LETTER TO THE EDITORSJON 2856years did not uncover an underly-ing cancer. Pyridostigmine par-tially improved the patient for the first 2 years, and then DAP wasintroduced with efficacy over the following 12 months. After anotherphase of deterioration, two series of IvIg infusions were useful for 2months. Then ephedrine sulfatewas prescribed at a dose of 200 mg/d and the improvement was so impressive that we decided toquantify the clinical and electro-physiological (Edx) changes beforeproceeding with ephedrine. The patient agreed to come forfive consecutive days. Muscle test-ing and Hammersmith motor ability score (HMS) were per-formed after the Edx tests. Edx studies were carried out by record-ing CMAP from the abductor digiti minimi muscle (ADM). After a rest period, negative CMAP amplitudewas evoked at rest and immediately after 15 s SET [4]. The clinical and Edx changes were recorded eachday with 3 repetitions of the fol-lowing 6 experimental conditions:no treatment, 90 minutes after taking 60 mg pyridostigmine, 25 mg 4-DAP, 100 mg ephedrine, pyridostigmine and DAP, ephe-drine and DAP. The results areshown in Fig.1. The highest HMS score correlates with the highest CMAP amplitude at rest obtainedduring the association of DAP and ephedrine. After obtaining these positive results, ephedrine (200 mg/d) and DAP (55 mg/d) were takencontinuously. Benefits were ob-served after the patient was re-viewed 1, 3 and 6 months after. Amoderate increase in blood pres-sure was observed.Ephedrine is a sympathomi-metic drug with highly activeadrenergic effects on the heart andvasculature [1], with untoward effects including hypertension andtachyphylaxis [9]. The precisemechanism of action in the muscleis only partially known. An in vitroCarlo CeredaThierry KuntzerThe potential use of ephedrine in Lambert-Eaton myasthenic syndromeClinical and electrophysiologicalevaluation Received: 6 March 2007Received in revised form:12 December 2007Accepted: 18 December 2007Published online: 13 June 2008Sirs: A Cochrane review on treatment of Lambert-Eaton myasthenic syndrome (LEMS) underscores the efficacy of 3,4-diaminopyridine (DAP) and of infusions of immunoglobulins (IvIg) [5]. The addition of pyrido-stigmine may enhance effects of DAP. Ephedrine, a controversialdrug used in the past to treatmyasthenia gravis without proven benefit [8], has recently been used to improve patients with synapticcongenital myasthenic syndrome [2]. Prompted by these observa-tions, we evaluated the efficacy of ephedrine in one patient with idiopathic LEMS.We describe a 60 year-oldfemale who developed progressive proximal limb muscle weaknessand generalized areflexia. A 300 %potentiation of the compoundmuscle action potential (CMAP) was demonstrated after a shortexercise test (SET) and antibodies against the voltage gated Ca2+channel were positive. Diagnostic works-up over the following 5 Edx study has shown that ephe-drine increases quantal release of acetylcholine (Ach) [10], and may cause an open-channel blockade of the Ach receptors [6], which cannotfully explain its beneficial effect. In a study using a rat model of myas-thenia, the ephedrine effects wereconsidered unrelated to neuromus-cular transmission but to suscepti-bility to arousal [7]. In the reported Edx trial of ephedrine in synapticcongenital myasthenic syndrome itwas concluded that ephedrine may exert a beneficial effect on musclefunction at a remote level as acentral effect [3]. In our patient weobserved a relative mismatch between the good clinical benefit (HMS) and surprisingly low CMAPat rest during treatment withephedrine alone (see Fig.1, day 5), and this probably reflects the cen-tral beneficial effect. Based on this, we can only speculate on a syner-gic, but useful, effect of ephedrinewith DAP. As a limiting factor it should be emphasised that (i) wedo not know the safe and therapeu-tic optimum dose of ephedrine perkg body weight, and (ii) that pa-tients should be monitored forpotential cardiovascular sideeffects. Further trials are therefore needed to study the efficacy and tolerability of ephedrine in LEMS. References 1. Andraws R, Chawla P, Brown DL (2005)Cardiovascular effects of ephedraalkaloids: a comprehensive review. Prog Cardiovasc Dis 47:217–2252. Bestue-Cardiel M, Sáenz de Cabezón-Alvarez A, Capablo-Liesa JL, et al. (2005) Congenital endplate acetylcho-linesterase deficiency responsive to ephedrine. Neurology 65:144–1463. Felice KJ, Relva GM (1996) Ephedrine in the treatment of congenital myas-thenic syndrome. Muscle Nerve 19:799–800C. Cereda, MD · T. Kuntzer, MD (,)Nerve-Muscle Unit, Neurology serviceCHU Vaudois and University of Lausanne1011 Lausanne, Switzerland Tel.: +41-21/3141291Fax: +41-21/3141290E-Mail: thierry.kuntzer@chuv.ch12604. Kuntzer T, Michel P (2004) Muscle membrane polarisation after provoca-tive tests, and after cooling: the normal CMAP changes to be expected. ClinNeurophysiol 115:1457–14635. Maddison P, Newsom-Davis J (2005)Treatment for Lambert-Eaton myas-thenic syndrome. Cochrane Database Syst Rev CD003279 6. Milone M, Engel AG (1996) Block of the endplate acetylcholine receptor channel by the sympathomimeticagents ephedrine, pseudoephedrine, and albuterol. Brain Res 740:346–3527. Molenaar PC, Biewenga JE, VanKempen GT, et al. (1993) Effect of ephedrine on muscle weakness in amodel of myasthenia gravis in rats. Neuropharmacology 32:373–3768. Patten BM (1978) Myasthenia gravis:review of diagnosis and management. Muscle Nerve 1:190–2059. Shekelle PG, Hardy ML, Morton SC, et al. (2003). Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 289:1537–154510. Sieb JP, Engel AG (1993) Ephedrine:effects on neuromuscular trans-mission. Brain Res 623:167–171             		'$%!"!	$%!"!  #%& %+$% !( ,( ! *%+)a b cdFig. 1 A to C shows examples of raw data of two superimposed traces, the smallest corresponding to the CMAPs evoked at rest and the largest those evoked immediately after a 15 s of maximal voluntary exercise test. Data with no treatment or OFF (A); 90 min after taking ephedrine (B), and after taking ephedrine and DAP (C). Note the hugepotentiation obtained in B, as well as the synergic effect of the combined treatment with ephedrine and DAP on the CMAP obtained at rest in C. D Diagram showing the relationship between Hammersmith motor score (HMS), and CMAP amplitude. CMAPs obtained at rest (solid lines) and after exercise (dashed lines) were repeated 3 times. Amplitude is expressed as minimal and maximal, and median values, in the following experimental conditions during 5 different days (D): no treatment (OFF), 90 min after taking (i) 60 mg pyridostigmine (Mestinon), (ii) 25 mg 3,4-diaminopyridine (DAP), (iii) 100 mg ephedrine (EPH), (iv) DAP and pyridostigmine (DAP+ Mestinon) and (v)ephedrine and DAP (EPH+DAP). The CMAPs obtained after exercise are quite similar in amplitude. The highest CMAP amplitude at rest was obtained at D6 (5.2 mV, DAP+ EPH), and correlates with the highest HMS score. The lowest CMAP amplitude obtained at rest was seen at D1 (Off), D2 (Mestinon) and D5 (EPH) (1.4 mV; 1.0 mV; 0.7 mV, respectively). Controversially, the HMS score under ephedrine is relatively high at day 5, probably reflecting the central effect of the drug 

The potential use of ephedrine in Lambert-Eaton myasthenic syndrome: Clinical and electrophysiological evaluation

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The potential use of ephedrine in Lambert-Eaton myasthenic syndrome: Clinical and electrophysiological evaluation

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