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Background: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods: Attainment of 'minimal symptom expression' was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. 'Minimal symptom expression' was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results: At REGAIN week 26, more eculizumab-treated patients achieved 'minimal symptom expression' versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved 'minimal symptom expression' increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved 'minimal symptom expression' (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions: Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained 'minimal symptom expression' based on patient-reported outcomes. 'Minimal symptom expression' may be a useful tool in measuring therapy effectiveness in gMG. Trial registration: ClinicalTrials.gov NCT01997229, NCT02301624. [ABSTRACT FROM AUTHOR]

Clinical phenotypes of persons with mitochondrial DNA (mtDNA) mutations vary considerably. Therefore, diagnosing mitochondrial myopathy (MM) patients can be challenging and warrants diagnostic guidelines. 31phosphorous magnetic resonance spectroscopy (31P-MRS) have been included as a minor diagnostic criterion for MM but the diagnostic strength of this test has not been compared with that of other commonly used diagnostic procedures for MM. To investigate this, we studied seven patients with single, large-scale deletions-, nine with point mutations of mtDNA and 14 healthy subjects, who were investigated for the following: 1) 31P-MRS of lower arm and leg muscles before and after exercise, 2) resting and peak-exercise induced increases of plasma lactate, 3) muscle morphology and -mitochondrial enzyme activity, 4) maximal oxygen uptake (VO2max), 5) venous oxygen desaturation during handgrip exercise and 6) a neurological examination. All MM patients had clinical symptoms of MM, > 2% ragged red fibers in muscle, and impaired oxygen desaturation during handgrip. Fourteen of 16 patients had impaired VO2max, 10/16 had elevated resting plasma lactate, and 10/11 that were investigated had impaired citrate synthase-corrected complex I activity. Resting PCr/Pi ratio and leg Pi recovery were lower in MM patients vs. healthy subjects. PCr and ATP production after exercise were similar in patients and healthy subjects. Although the specificity for MM of some 31P-MRS variables was as high as 100%, the sensitivity was low (0–63%) and the diagnostic strength of 31P-MRS was inferior to the other diagnostic tests for MM. Thus, 31P-MRS should not be a routine test for MM, but may be an important research tool. [ABSTRACT FROM AUTHOR]

Cycle exercise has repeatedly been used to diagnose patients suspected of having mitochondrial myopathy (MM), in whom exercise intolerance and lactic acidosis are common. No standardized test, however, has been established. We evaluated the diagnostic value of incremental and constant workload (20 min at 65 % VO(2max)) cycle tests for the diagnosis of MM. Plasma lactate and oxidative capacity (VO(2) and workload) were measured in 15 well-characterized MM patients during cycling. Findings were compared with those in 10 myotonic dystrophy patients and 18 sedentary, healthy subjects. All MM patients had ragged red or COX-negative fibers on muscle biopsy. VO(2max) and maximal workload were lower in MM than in control groups (P < 0.02). Resting plasma lactate was higher in MM than in control groups (P < 0.005; sensitivity = 93 %; specificity = 85 %), while exercise-induced increases in plasma lactate were only higher during the constant workload protocol in MM patients vs. control groups (P < 0.05; sensitivity = 27 %; specificity = 86 %). The findings indicate that the diagnostic value of a constant workload protocol is superior to an incremental cycle test, but that the test is less sensitive for MM than simple testing of resting lactate and muscle morphology. Cycle testing of MM patients remains an important research tool, but should not be a standard diagnostic procedure for MM.