br Conclusion br Conflicts of Interest Disclosures br Acknow

Conclusion
Conflicts of Interest/Disclosures
Acknowledgement This study was funded by the Ministry of Science of the Republic of Serbia (grant #175083).
Introduction Myasthenia gravis (MG) is an antibody-mediated, neuromuscular transmission disorder, where the targets are postsynaptic proteins, primarily the skeletal muscle TAPI-1 receptor (AchR) and the muscle-specific tyrosine kinase (MuSK). The disease is characterized by fluctuating skeletal muscle weakness. Muscle atrophy may occur in approximately 10% of patients, usually those with long-standing disease or after chronic corticosteroid treatment, and it is rare early in the course of MG. However, in MuSK-MG, muscle atrophy, particularly of the facial and bulbar muscles, can be evident early and occur prior to corticosteroid treatment.[3], [4] We report a patient with AchR-positive MG of short duration and prior to commencement of steroid therapy, with MRI evidence of muscle atrophy.
Case report A 63-year-old male patient presented with a six-month history of nasal speech, dysarthria, chewing and deglutition difficulties, and difficulty in holding up his head. The symptoms were characterized by diurnal variation, exacerbation with fatigue and improvement with rest. Neurological examination revealed weakness of orbicularis oculi, orbicularis oris and neck extensor and flexor muscles, with no obvious muscle atrophy. There was also proximal upper limb weakness, but no lower limb or respiratory muscle involvement. Repetitive nerve stimulation of orbicularis oculi and trapezoid was positive for MG. Needle electromyography (EMG) of cervical paraspinal, sternocleidomastoid, trapezoid and biceps brachii muscles revealed short motor unit action potentials (MUAP) without spontaneous activity and without increased polyphasia. The nerve conduction study was normal. Serum AchR antibodies (Abs) were positive with a titer of 117nM (normal: <0.2nM), while MuSK Abs were negative. Laboratory investigation, including creatine kinase, was normal. A CT scan of the mediastinum was normal. The diagnosis of late onset, AchR-positive generalized MG was established. Before initiating treatment we performed MRI to assess muscle wasting in the cervical and bulbar muscles. The study revealed marked atrophy and fatty replacement (evident on T2-weighted MRI with fat saturation) of the posterior cervical, paraspinal, sternocleidomastoid and masseter muscles (particularly left) (Fig. 1). Pyridostigmine (300mg per day) resulted in a partial response, while adding prednisolone up to 50mg once per day led to dramatic clinical improvement. Twelve weeks after the initiation of steroids, the patient reported no symptoms and neurological examination revealed only mild signs of myasthenic weakness.
Discussion Muscle atrophy is an unusual finding in patients with MG. Oosterhuis and Bethlem reported muscle atrophy in patients with generalized MG with neurogenic histopathological lesions of the atrophic limb muscles. However, the antibody-status to AchR or to MuSK was not known at the time of the study. In an MRI study, Farrugia et al. reported wasting of the facial and bulbar muscles in patients with AchR-MG and MuSK-MG, but these findings only reached statistical significance in the MuSK-MG cohort. Although chronic moderate–high dose corticosteroid treatment may be a contributing factor, in vitro data indicate that MuSK Abs per se may also predispose to muscle atrophy. Some studies in the limb muscles of patients with MG have shown shorter MUAP. The authors of a quantitative EMG study of facial muscles in patients with MG with MuSK Abs proposed that facial muscle atrophy in MuSK-MG is not a neurogenic, but a myopathic, process consisting of either muscle fiber shrinkage or loss of muscle fibers from motor units.
Introduction Neural development and plasticity require synapse assembly and disassembly, but it is not known how the differentiation of pre- and postsynaptic elements is coordinated and how precise patterning and localization of synaptic connectivity is achieved. Reciprocal interactions mediated by the asymmetric signaling of cell adhesion molecules or putative diffusible messengers are thought to shape synaptic junctions. Additional signals may originate from glial cells that are in close proximity to synaptic specializations (Goda and Davis, 2003). In case of the neuromuscular junction (NMJ) in skeletal muscle of vertebrates, the generation of knock-in mouse models has created new opportunities to characterize putative presynaptic and postsynaptic regulators and to investigate how acetylcholine receptor (AChR)-mediated activity contributes to synapse development and plasticity (Kummer et al., 2006).