Autoimmunity at the neuromuscular synapse: pathophysiology and disease course

Lipka, A.F. (2021)

Doctoral Thesis

This thesis addresses several pathophysiological and clinical aspects of both the Lambert-
Eaton myasthenic syndrome (LEMS, introduced in chapter 1) and myasthenia gravis (MG).
In chapter 2, the search for new LEMS associated small cell lung cancer (SCLC) markers is described, leading to the discovery of ERC1 as a new antigen associated with LEMS.
In chapter 3, a literature review of screening methods for SCLC in LEMS is presented, as
well as the role of associated SOX1 antibodies in SCLC-LEMS patients.
In chapter 4 long-term follow-up, functional impairment and quality of life in LEMS
patients are described. We also report a normal survival in LEMS patients without associated tumour as well as an improved tumour survival in SCLC-LEMS patients.
In chapter 5, we report that lowering the cut-off value for increment from 100% to 60% increases sensitivity for diagnosis of LEMS, without a negative effect on the specificity.
Chapter 6 reports that a lower initial compound muscle action potential amplitude is a marker of more severe disease in AChR MG.
In chapter 7, we show a small symptomatic effect of ephedrine as a symptomatic treatment in MG patients, in a placebo-controlled, double-blind, randomised, multiple crossover series of n-of-1 trials.

• Lambert-Eaton myasthenic syndrome
• Myasthenia gravis
• Neuroimmunology
• Neuromuscular synapse

• All authors: Lipka, A.F.
• Supervisor: Verschuuren, J.J.G.M.
• Co-supervisor: Titulaer, M.J.; Huijbers, M.G.M.
• Committee: Hiemstra, P.S.; Engelen, B.G.M. van; Kooi, A.J. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center [LUMC], Leiden University
• Date: 2021-12-15
• ISBN (print): 9789464235067