Das Lambert-Eaton-Myasthenie-Syndrom: ein Überblick

Zusammenfassung

Das Lambert-Eaton-Myasthenie-Syndrom (LEMS) hat eine Prävalenz von etwa 5/1 000 000 und ist damit im Vergleich zur Myasthenia gravis (MG) ca. 10 – 20-mal seltener. Obwohl LEMS viele Ähnlichkeiten zur Myasthenia gravis aufweist, gibt es wichtige Unterschiede. Klinisch besteht eine vorwiegend proximal betonte belastungsabhängige Muskelschwäche, die bis hin zu einer respiratorischen Insuffizienz führen kann und häufig mit autonomen Störungen assoziiert ist. Ursächlich dafür sind Auto-Antikörper, welche gegen spannungsabhängige Kalziumkanäle (VGCC) vom P/Q-Typ an der Präsynapse gerichtet sind. Die Diagnosesicherung beruht vor allem auf der Detektion des pathologischen anti-VGCC Antikörpers sowie dem spezifischen Nachweis eines Inkrements von mindestens 60 % in der elektrophysiologischen Untersuchung eines betroffenen Muskels. Ein Inkrement ist dabei durch eine Steigerung des in Ruhe reduzierten Muskelsummenaktionspotenzials entweder nach maximaler Willkürinnervation oder hochfrequenter (≥ 20 Hz) Stimulation definiert. In einem Drittel der Patienten ist das LEMS paraneoplastischer Ätiologie, eine umfassende Tumorsuche nach Diagnosestellung ist daher notwendig. Klinisch gibt es einige Unterschiede zwischen dem paraneoplastischen (pLEMS) und dem rein autoimmunen (aiLEMS) Lambert-Eaton-Syndrom, die Hinweise geben können für die Ätiologie. Einen Anhalt dafür liefert der DELTA-P-Score und der SOX1-Antikörperstatus. Die häufigste zugrunde liegende Tumorerkrankung ist das kleinzellige Lungenkarzinom. Die Therapie basiert zunächst auf der Unterscheidung zwischen paraneoplastischer und autoimmuner Genese. pLEMS erfordert die Therapie der Tumorerkrankung. In der Regel profitieren aiLEMS- wie pLEMS-Patienten von einer symptomatischen Therapie mittels 3,4-Diaminopyridin (3,4-DAP), ggf. ergänzend Pyridostigmin sowie einer immunsuppressiven Langzeit-Therapie. Krisenhafte Verschlechterungen werden analog zur Myasthenia gravis mit Immunglobulinen, Plasmapherese oder Immunadsorption behandelt. Basierend auf positiven Erfahrungsberichten können auch moderne immunmodulatorische Ansätze, z. B. mit therapeutischen Antikörpern wie dem anti-CD20-Antikörper Rituximab, bei therapierefraktären Verläufen sinnvoll sein. Die Langzeitprognose des autoimmunen LEMS für eine klinische Stabilisierung mit weitgehender (pharmakologischer) Remission ist unserer Erfahrung nach gut, allerdings bestehen bei etwa 75 % deutliche Einschränkungen der Lebensqualität. Die Prognose der tumorassoziierten Form wird zu einem großen Teil von der Tumorerkrankung selbst und deren Therapie bestimmt. Kurative Verläufe der Tumorerkrankung und weitgehende Remission des pLEMS sind nicht selten.

Abstract

The Lambert-Eaton myasthenic syndrome (LEMS) has a prevalence of around 5/1 000 000 and is around 10 – 20 times rarer than myasthenia gravis (MG). Although LEMS does have a number of similarities to MG, there are important differences. The syndrome is characterized by a mostly proximally localised exercise-induced muscle weakness that can lead to respiratory failure, often accompanied by autonomous dysfunction. Disease symptoms are caused by autoantibodies directed against P/Q type voltage-gated calcium channels (VGCC) that are expressed in the presynaptic motor nerve terminals. The diagnosis of LEMS is based on the detection of the pathogenic anti-VGCC antibodies as well as the observation of an increment of at least 60 % in the electrophysiological examination of an affected muscle. An increment is defined by an increase of the at-rest reduced compound muscle action potential (CMAP) either after voluntary maximal innervation or after high frequency (≥ 20 Hz) stimulation. In almost one-third of patients, LEMS is of paraneoplastic origin. Therefore, an intensive tumour screening is necessary after diagnosis. There are some differences in the clinical presentation between paraneoplastic (pLEMS) and the exclusively autoimmune (aiLEMS) form of LEMS. With respect to this, the DELTA-P-Score and the detection of SOX1-antibody are important. The most frequent tumour associated with LEMS is small cell lung carcinoma (SCLC). Therapy is based on the initial distinction between paraneoplastic and autoimmune etiology. pLEMS requires therapy of underlying neoplasia. Usually, aiLEMS as well as pLEMS patients respond well to 3,4 diaminopyridine (3,4-DAP), often augmented with pyridostigmine. Similar to treatment of myasthenia gravis, long-term immunosuppressive treatment is usually required to control symptoms effectively. Myasthenic crisis in LEMS can be controlled by intensive care and immunoglobulins, plasmaphereses or immunoadsorption. Based on case reports, more specific immunomodulatory treatment approaches such as the B-cell-depleting therapeutic antibody rituximab should be considered in therapy refractory courses of LEMS. Long-term prognosis of autoimmune LEMS with respect to clinical stabilization with (pharmacological) remission is good, although in around 75 % of patients, significant reductions in quality of life remain. Prognosis of tumour-associated LEMS is largely determined by the tumour and its effective therapy. Curative treatment of the tumour disease as well as complete remission of pLEMS is possible.

Schlüsselwörter

Lambert-Eaton-Myasthenie-Syndrom - 3,4-Diaminopyridin - anti-VGCC-Antikörper - DELTA-P-Score

Keywords

Lambert-Eaton myasthenic syndrome - 3,4-diaminopyridine - anti-VGCC antibodies - DELTA-P-Score

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