Myopathy

To the Editor:

We report on a physician-patient (C.H.W.) with a diagnosis of undifferentiated autoimmune disease, pandysautonomia, and presumed mitochondrial dysfunction (no muscle biopsy performed). Retired on disability in 1995, she has severe exercise intolerance and was unable to perform instrumental activities of daily living and, at times, even basic activities of daily living, despite having no underlying cardiac or pulmonary disease. Additional symptoms suggestive of mitochondrial myopathy include marked dyspnea and quadriceps pain with mild exercise. This quadriceps pain becomes more severe immediately following long airplane trips, but can be significantly reduced by using oxygen while on the plane (purchased for individual use prior to take-off).

The presumed mitochondrial dysfunction was diagnosed with exercise pulmonary function testing performed on room air and repeated 48 h later on supplemental oxygen (100%). The second exercise test used as the target heart rate the maximal heart rate attained during the testing done on room air. At rest, the baseline pyruvate level was 0.13 mmol/L (normal value, 0.00 to 0.08 mmol/L) and lactate level was 1.6 mmol/L (normal value, 0.5 to 2.2 mmol/L). With exercise, 4.34 min of a modified Bruce protocol to 4.5 metabolic equivalents (METs), the pyruvate level rose to 0.16 mmol/L and lactate level to 10.3 mmol/L. Table 1 displays relevant values for both exercise tests. Urine collected in the 24 h following each exercise test was positive for myoglobin.

As shown in Table 1, the anaerobic threshold and maximal heart rate were similar in both testing conditions. However, the total oxygen uptake (V[O.sub.2]), minute ventilation, and METs were markedly improved with supplemental oxygen. Although lactic acid accumulation still occurred, it was substantially less than in the room air testing.

These data suggested that a trial of therapeutic oxygen might improve daily function. The patient has been using supplemental oxygen for exercise, in the car, while sleeping, and/or "not feeling well" for the past 18 months. She uses variable flow between 2 L/min and 6 L/min with a mask and concentrator device at home, or a demand-delivery system with nasal prongs and portable tanks. Her functional capacity has gradually improved, and her prednisone dose has been substantially decreased for the first time in 8 years. She can now drive around town, walk in a shopping mall, and perform some household chores. In addition, the hair that had previously disappeared from her extremities (thought to be secondary to either the autoimmune syndrome disease or medication side effect) has regrown. Prior to oxygen therapy, her soft tissues in the extremities were painful with a boggy firmness, a fibromyalgia-like finding also thought to be part of the autoimmune syndrome. This symptom has gradually, but significantly, improved through a combination of body work (osteopathy and massage) and oxygen therapy. Prior to receiving supplemental oxygen, the same type of body work had been only minimally effective.

Researchers (1-5) have reported exercise intolerance and pulmonary function in patients with mitochondrial dysfunction. Reports of aerobic training have documented increased oxidative capacity in patients with mitochondrial myopathies. (6-7) One aerobic study (7) suggested that the cellular basis of improved oxygen utilization is related to training-induced mitochondrial proliferation. However, in this same study, genetic analysis indicated a trend toward preferential proliferation of mutant genes relative to wild-type mitochondrial DNA. These investigators raise concerns about the long-term benefits of aerobic conditioning in these patients. (7) Previous reports of aerobic training have not described any trials of therapeutic oxygen for mitochondrial myopathy. This case report suggests that supplemental oxygen can enable patients to perform higher levels of cardiopulmonary work with less lactic acid accumulation than room air alone. The use of supplemental oxygen may not only improve functional capacity and certain physiologic abnormalities but may also minimize the mitochondrial stress, which has been postulated to increase the proportion of mutant mitochondria.

Correspondence to: Carol Hutner Winograd, MD, 746 Esplanada Way, Stanford, CA 94305

REFERENCES

(1) Flaherty KR, Weld J, Weisman IM, et al. Unexplained exertional limitation: characterization of patients with a mitochondrial myopathy. Am J Respir Crit Care Med 2001; 164:425-432

(2) Hooper RG, Thomas AR, Kearl RA. Mithocondrial enzyme deficiency causing exercise limitation in normal-appearing adults. Chest 1995; 107:317-322

(3) Clay AS, Behnia M, Brown KK. Mithochondrial disease: a pulmonary and critical care medicine perspective. Chest 2001, 120:634-648

(4) Andreu AL, Hanna MG, Reichmann H, et al. Exercise intolerance due to mutations in cytochrome b gene of mitochondrial DNA. N Engl J Med 1999; 341:1037-1044

(5) Dandurand RJ, Matthews PM, Arnold DL, et al. Mitochondrial disease: pulmonary function, exercise performance, and blood lactate levels. Chest 1995; 108:182-189

(6) Taivassalo T, De Stefano N, Chen J. Short-term aerobic training response in chronic sympathies. Muscle Nerve 1999; 22:1239-1243

(7) Taivassalo T, Shoubridge EA, Chen J, et al. Aerobic conditioning in patients with mitochondrial sympathies: physiological, biological, and genetic effects. Ann Neurol 2001; 50.133-141

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