David B. Olsen

Aerobic training improves exercise performance in facioscapulohumeral muscular dystrophy

Exercise programs have been shown to increase strength and endurance in patients with myopathic disorders. The authors investigated the effect of aerobic training in patients with facioscapulohumeral dystrophy (FSHD). Twelve weeks of low-intense aerobic exercise improved maximal oxygen uptake and workload with no signs of muscle damage. The authors conclude that aerobic training is a safe method to increase exercise performance in patients with FSHD.

Aerobic training in patients with myotonic dystrophy type 1

The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing and muscle morphology before and after training. Patients increased their maximal oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter increased significantly, and creatine kinase did not increase with training. The study indicates that aerobic training is safe and can improve fitness effectively in patients with myotonic dystrophy. Ann Neurol 2005;57:754–757

Oxidative capacity correlates with muscle mutation load in mitochondrial myopathy.

The purpose of this study was to investigate the correlation between the level of mutated mitochondrial DNA in muscle and oxidative capacity in 24 patients with mitochondrial myopathy (MM). Maximal oxygen uptake (VO2max), workload (Wmax), and venous plasma lactate levels were measured during an incremental cycle test to exhaustion in 17 patients with point mutations of mtDNA and in seven with single, large‐scale deletions of mtDNA (chronic progressive external ophthalmoplegia [CPEO]). Results were compared with those in 25 healthy matched subjects. The mutation load in MM patients was 67 ± 5% (range, 29 – 99%). VO2max and Wmax correlated with percentage of heteroplasmy (r > 0.82; p < 0.005) and were lower in patients versus healthy subjects (p < 0.000005). Exercise‐induced peak increases in heart rate, ventilation, and resting plasma lactate levels correlated with muscle mutation load (r > 0.71; p < 0.005). Exercise‐induced increases in plasma lactate correlated with muscle mutation load in CPEO patients (r = 0.95; p < 0.005). Impaired oxidative capacity and ragged red muscle fibers were found in CPEO and 3243A→G patients with mutation loads as low as 45 and 57%, respectively. The study indicates that oxidative capacity correlates directly with skeletal muscle mutation load in MM patients, and that the mutation threshold level for impaired oxidative metabolism in MM patients is lower than found in in vitro studies. Ann Neurol 2003

Exercise tolerance in carnitine palmitoyltransferase II deficiency with IV and oral glucose

Background Patients with carnitine palmitoyltransferase II (CPT II) deficiency often experience muscle pain and myoglobinuria during prolonged exercise because of impaired oxidation of long-chain fatty acids. Objective To investigate whether IV or oral glucose can improve exercise tolerance in CPT II deficiency. Methods Five patients with CPT II deficiency and healthy matched volunteers were investigated on a cycle ergometer at a constant workload of 60% of Vo2max. Perceived exertion, heart rate, and venous plasma glucose and insulin levels were monitored. The study was randomized, placebo controlled, single blind, and crossover. Glucose and placebo were administered both orally and IV in patients and IV in healthy subjects. Results In patients with CPT II, exercise duration was prolonged by 28 ± 8% (p = 0.02), and perceived exertion (p = 0.05) and heart rate (p = 0.09) were lowered by glucose infusion. In contrast, IV glucose resulted in higher heart rate during exercise in healthy subjects. Oral glucose and placebo resulted in the same exercise duration, perceived exertion, and heart rate in patients. Plasma glucose and insulin were consistently elevated during exercise by oral and IV glucose vs placebo, but plasma glucose was higher and insulin lower in IV vs oral glucose studies in patients (p = 0.02). Conclusion Exercise tolerance is markedly improved by a glucose infusion in patients with CPT II deficiency, but because of lower glucose availability and higher insulin levels that inhibit muscle glycogenolysis, the patients cannot achieve this effect themselves by oral glucose ingestion.

Cycle ergometry is not a sensitive diagnostic test for mitochondrial myopathy

Abstract. 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 % VO2max) cycle tests for the diagnosis of MM. Plasma lactate and oxidative capacity (VO2 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. VO2max 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.

Muscle structural changes in mitochondrial myopathy relate to genotype

Abstract.It is well known that morphological changes at the cellular level occur in muscle of patients with mitochondrial myopathy (MM), but changes in muscle structure with fat infiltration and gross variation of muscle fiber size with giant fibers, normally encountered in the muscular dystrophies, have typically not been associated with mitochondrial disease. We investigated gross and microscopic muscle morphology in thigh muscles by muscle biopsy and MRI in 16 patients with MM, and compared findings with those obtained in muscular dystrophy patients and healthy subjects. Changes of muscle architecture, similar to those found in the group of muscular dystrophy patients occurred consistently in patients with a high mutation load for single, largescale deletions of mtDNA, but were absent in all patients with the 3243A→G mtDNA point mutation. Dystrophic changes of muscle architecture were also present in one MM patient with a unique, sporadic mutation in the mtDNA tRNAMet gene. These findings provide evidence that morphological changes in muscle of MM patients are common and may resemble those of muscular dystrophies, but that development of dystrophic-like changes in muscle relate to genotype.