CONTROL OF BREATHING IN PATIENTS WITH MYASTHENIA-GRAVIS

Control of breathing has seldom been investigated in patients with myasthenia gravis (MG). We evaluated lung volumes and respiratory muscle strength by measuring maximal inspiratory (MIP) and expiratory (MEP) pressures in 12 patients with moderate generalized (IIb) MG before and after an orally administered therapeutic dose (120 mg) of Mestinon(TM), and in 11 age- and sex-matched normal subjects. Breathing pattern, mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (EMGd) and intercostal (EMGint) muscles were evaluated during both room-air breathing and hypercapnic rebreathing. Before Mestinon, patients exhibited a slight decrease in VC, and normal TLC and FEV1/NC ratio. Compared with the normal control group, patients also exhibited respiratory muscle weakness (marked decrease in MIP and MEP; p<0.001 for both), and more rapid and shallower breathing (RSB): lower tidal volume (VT), inspiratory time (TI), expiratory time (TE), and greater respiratory frequency (f); mean inspiratory flow (VT/TI) and P0.1 were slightly supernormal, whereas both EMGd and EMGint were significantly higher in patients. During hypercapnic rebreathing, ventilation (VE) (p<0.01), VT (p<0.001), VT/TI, (p<0.003), P0.1 (p<0.003), and EMGd (p<0.001) response slopes to increasing PCO2 were found to be lower, whereas EMGint response slope was normal. At 60 mm Hg of PCO2 in the two groups the difference in terms of breathing pattern, P0.1, and EMGd were similar to that observed during room-air breathing. After Mestinon, VC (p<0.005), MIP (p<0.02), and MEP (p<0.01) significantly increased, whereas spontaneous breathing remained unchanged. Conversely, VE, VT, VT/TI, P0.1, and EMGd, but not EMGint, did significantly Increase during rebreathing (p<0.05 to p<0.003), whereas TI remained unchanged. Changes in muscle strength with Mestinon did not significantly relate to changes in either VE or VT during hypercapnia. We conclude that in spontaneously breathing patients with grade lib MG, inspiratory drive is modulated into a tachypneic pattern of respiration and a smaller VT. A disorder in neuromuscular transmission is probably the reason for the apparent decrease in EMGd and ventilatory output during chemically loaded breathing. In the latter condition Mestinon appears to normalize the drive to breathe, leaving the switching inspiratory mechanism substantially unmodified. Respiratory drive is not likely to be reduced at this stage of the disease.