Clinical, electrophysiological, pathogenetic and imunological specificities of aquired autoimmune myasthenia gravis associated with antibodies against muscle specific tyrosine kinase

Cilj: da se kod bolesnika sa miastenijom gravis udruženom sa antitelima prema mišićspecifičnoj tirozin kinazi (MuSK MG) analiziraju kliničke, elektrofiziološke, patogenetske i imunološke specifičnosti u odnosu na bolesnike sa miastenijom gravis udruženom sa antitelima prema nikotinskom acetilholinskom repetoru (AChR MG). Metodologija: Analizirano je 31 MuSK MG i 28 AChR MG bolesnika, kod kojih je sprovedena detaljna klinička obrada, elektrofiziološko ispitivanje, magnetna spektroskopija (MRS) mišića jezika, testiranje autonomnog nervnog sistema i HLA (humani leukocitni antigen) tipizacija. Rezultati: Dominantna klinička prezentacija MuSK MG je bila okulobulbarna i mimična slabost, a teške forme bolesti su zabeležene kod preko 80% bolesnika. Prostigminski test je bio pozitivan kod 77% MuSK MG u odnosu na 100% AChR MG pacijenata, a hipersenzitvna reakcija na inhibitore acetilholinesteraze je bila prisutna kod 39% MuSK MG bolesnika, dok je u grupi AChR MG pacijenata ona registrovana kod svega 4% bolesnika. Timus je kod bolesnika sa MuSK MG bio normalan u 67% ili atrofičan u 33% slučajeva, dok je kod AChR MG bolesnika najčešća bila limfofolikualrna hiperpalzija (80%). Test repetitivne stimulacije je bio ređe pozitivan kod MuSK u odnosu na AChR bolesnike (52%:93%), i to najčešće na mišićima lica i proksimalnim mišićima ekstremiteta. SFEMG je bio pozitivan kod preko 90% obolelih obe grupe, kod MuSK MG bolesnika češće na licu. Prisustvo miopatije je kod MuSK MG bolesnika bilo znatno češće u odnosu na pacijente sa AChR MG. Kod MuSK MG miopatija je bila prisutna u mišićima lica kod čak 80% pacijenata, dok je u mišićima ekstremiteta ona registrovana kod trećine obolelih. Za razliku od ovoga kod AChR MG bolesnika miopatske promene su zabeležene kod svega 7% pacijenata na mišićima ekstremiteta i kod 32% na mimičnim mišićima. MRS mišića jezika je kod MuSK MG bolesnika opisana intramiocelularna masna infiltracija kod čak 85% obolelih, dok je kod AChR MG bolesnika ona zabeležena kod svega 20% pacijenata. Dobar ishod bolesti je evidentiran kod bolesnika obe grupe, ali je najveći broj MuSK MG bolesnika zahtevao produženo lečenje imunosupresivnom terapijom...Objectives: To analyze clinical, electrophysiological, pathogenetic and immunological specificities of the patients with myasthenia gravis associated with anti-muscle specific tyrosine kinaze antibodies (MuSK MG) in relation to the patients with myasthenia gravis associated with anti-nicotinic acetylcholine receptor antibodies (AChR MG). Methods: We analyzed 31 MuSK MG i 28 AChR MG patients, in whom we conducted detailed clinical and electrophysiological examination, proton magnetic resonance spectroscopy (MRS) of the intrinsic tongue muscles, autonomic nervous system testing and HLA (humane leukocyte antigen) typing. Results: Predominant clinical presentation of MuSK MG was oculobulbar and facial weakness, and severe disease forms were present in over 80% of patients. Neostigmine testing was positive in 77% of MuSK MG in relation to the 100% of AChR MG patients, and hypersensitive reaction to acetylcholine esterase inhibitors was registered in 39% of MuSK MG patients and only in 4% of AChR MG patients. Thymus was normal (67%) or atrophic (33%) in patients with MuSK MG, while in patients with AChR MG the most frequent finding was lymphopholiculare hyperplasia (80%). Repetitive nerve stimulation test was rarely positive in MuSK in relation to the AChR MG patients (52%:93%), most frequently in facial and proximal limb muscles. Single fibre electromyography was positive in over 90% of patients from both groups, in MuSK MG patients more often in facial muscles. The presence of myopathy was more frequent in MuSK compared to AChR MG patients. It was registered in the facial muscles in 80%, and in limb muscles in 30% of MuSK MG patients, while it was present in 7% of AChR MG patients in the limb muscles and in 32% of AChR MG patients in the facial muscles. In accordance to this finding, examination of the tongue muscles with MRS showed intramyocellular fatty infiltration in 85% of MuSK and 20% of AChR MG patients. Good disease outcome was observed in the patients from both groups, but the majority of the MuSK MG patients were dependant on prolonged immunosupressive therapy..