Benita Klaus, Patrick Müller, Nora van Wickeren, Milos Dordevic, Marlen Schmicker, Yael Zdunczyk, Tanja Brigadski, Volkmar Lessmann, Stefan Vielhaber, Stefanie Schreiber, Notger Germar Müller

• Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 +/- 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 +/- 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T-1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showedMyasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 +/- 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 +/- 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T-1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail. Klaus et al. compared myasthenia gravis patients to matched healthy control subjects and identified functional alterations in memory functions as well as structural alterations in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus.…