Volume 10, Issue 12, Pages (December 2011)

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Volume 10, Issue 12, Pages 1098-1107 (December 2011) Lambert–Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies Dr Maarten J Titulaer, MD, Bethan Lang, PhD, Prof Jan JGM Verschuuren, MD The Lancet Neurology Volume 10, Issue 12, Pages 1098-1107 (December 2011) DOI: 10.1016/S1474-4422(11)70245-9 Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 1 Spreading of symptoms in patients with NT-LEMS and SCLC-LEMS Frequency of symptoms at 3 months (A) and 12 months (B) in patients with NT-LEMS, and frequency of symptoms at 3 months (C) and 12 months (D) in patients with SCLC-LEMS. The percentages describe the approximate proportion of patients who have that symptom within the given timeframe. NT=non-tumour. LEMS=Lambert–Eaton myasthenic syndrome. SCLC=small-cell lung cancer. The Lancet Neurology 2011 10, 1098-1107DOI: (10.1016/S1474-4422(11)70245-9) Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 2 Pathophysiology of LEMS and effects of symptomatic treatment (A) Normal depolarisation of the presynaptic nerve terminal by ion channels leads to influx of calcium ions and subsequent release of ACh-containing vesicles; ACh binds to the ACh receptor, leading to depolarisation of the postsynaptic synapse and ultimately to muscle contraction. (B) In LEMS, VGCC antibodies block calcium influx, leading to reduced ACh vesicle release from the presynaptic membrane; therefore, reduced ACh is available to bind to postsynaptic ACh receptors. (C) Treatment with 3,4-diaminopyridine (red triangle) blocks the efflux of potassium ions, prolonging the duration of depolarisation. Longer depolarisation keeps the pathologically affected calcium channels open longer, increasing calcium ion influx and intracellular calcium concentration and thereby improving the ability of the ACh vesicles to fuse and release neurotransmitter. LEMS=Lambert–Eaton myasthenic syndrome. ACh=acetylcholine. VGCC=voltage-gated calcium channels. DAP=diaminopyridine. The Lancet Neurology 2011 10, 1098-1107DOI: (10.1016/S1474-4422(11)70245-9) Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 3 Predicted percentage of SCLC in patients with LEMS, based on the Dutch-English LEMS Tumor Association Prediction (DELTA-P) score The DELTA-P score is calculated as a sum score according to the different categories listed. The DELTA-P score can range from 0 to 6. Point sizes are proportional to the number of patients with a specific score, which is also represented by the percentage beside the circle. Vertical bars show SEM. SCLC=small-cell lung cancer. LEMS=Lambert-Eaton myasthenic syndrome. Reproduced from Titulaer and colleagues,3 by permission of the American Society of Clinical Oncology. The Lancet Neurology 2011 10, 1098-1107DOI: (10.1016/S1474-4422(11)70245-9) Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 4 Flowchart of recommended screening for SCLC in patients with LEMS3,16,70 SCLC=small-cell lung cancer. LEMS=Lambert–Eaton myasthenic syndrome. FDG-PET= 18F-fluorodeoxyglucose PET. NT=non-tumour. The Lancet Neurology 2011 10, 1098-1107DOI: (10.1016/S1474-4422(11)70245-9) Copyright © 2011 Elsevier Ltd Terms and Conditions

Figure 5 Treatment scheme for LEMS LEMS=Lambert–Eaton myasthenic syndrome. DAP=diaminopyridine. SCLC=small-cell lung cancer. The Lancet Neurology 2011 10, 1098-1107DOI: (10.1016/S1474-4422(11)70245-9) Copyright © 2011 Elsevier Ltd Terms and Conditions