Myophosphorylase deficiency impairs muscle oxidative metabolism

We studied oxidative metabolism during bicycle exercise in 4 patients with myophosphorylase deficiency. Maximal oxygen uptake (VO2max) was low (14.0 +/- 1.4 ml X kg-1 X min-1, mean +/- SE) compared with that in normal subjects (37.7 +/- 1.9; n = 12) and patients with myalgia (24.9 +/- 1.8; n = 10). Carbohydrate oxidation, as estimated by the respiratory exchange ratio (R), was low relative to workload (max R, mean +/- SE: McArdle's disease, 0.96 +/- 0.02; normal subjects, 1.13 +/- 0.02; myalgia, 1.09 +/- 0.02). Intravenous glucose administration increased maximal oxygen uptake about 20% in those with McArdle's disease, but both VO2max and R remained lower than in control subjects. These findings suggest that the capacity for dynamic exercise in McArdle's disease is limited by the availability of oxidative substrate, and indicate that blood glucose is unable to substitute fully for muscle glycogen as an oxidative fuel. We also found that exercise cardiac output (Q) was excessive relative to oxygen uptake in affected patients (delta Q/delta VO2, mean +/- SE: McArdle's disease, 11.6 +/- 1.7; normal subjects, 4.8 +/- 0.2; myalgia, 5.6 +/- 0.2). This hyperkinetic circulation in exercise may serve to increase the delivery of blood-borne oxidative substrate to working muscle.     

Venous oxygen levels during aerobic forearm exercise: An index of impaired oxidative metabolism in mitochondrial myopathy.

A cardinal feature of impaired skeletal muscle oxidative metabolism in mitochondrial myopathies is a limited ability to increase the extraction of O(2) from blood relative to the increase in O(2) delivery by the circulation during exercise. We investigated whether aerobic forearm exercise would result in an abnormal increase in venous effluent O(2) in patients with impaired skeletal muscle oxidative phosphorylation attributable to mitochondrial disease. We monitored the partial pressure of O(2) (PO(2)) in cubital venous blood at rest, during handgrip exercise, and during recovery in 13 patients with mitochondrial myopathy and exercise intolerance and in 13 healthy control and 11 patient control subjects. Resting and recovery venous effluent PO(2) were similar in all subjects, but during exercise venous PO(2) paradoxically rose in mitochondrial myopathy patients from 27.2 +/- 4.0mmHg to 38.2 +/- 13.3mmHg, whereas PO(2) fell from 27.2 +/- 4.2mmHg to 24.2 +/- 2.7mmHg in healthy subjects and from 27.4 +/- 9.5mmHg to 22.2 +/- 5.2mmHg in patient controls. The range of elevated venous PO(2) during forearm exercise in mitochondrial myopathy patients (32 to 82mmHg) correlated closely with the severity of oxidative impairment as assessed during cycle exercise. We conclude that measurement of venous PO(2) during aerobic forearm exercise provides an easily performed screening test that sensitively detects impaired O(2) use and accurately assesses the severity of oxidative impairment in patients with mitochondrial myopathy and exercise intolerance.     

<Superscript>31</Superscript>P-MRS of skeletal muscle is not a sensitive diagnostic test for mitochondrial myopathy

Clinical phenotypes of persons with mitochondrial DNA (mtDNA) mutations vary considerably. Therefore, diagnosing mitochondrial myopathy (MM) patients can be challenging and warrants diagnostic guidelines. (31)phosphorous magnetic resonance spectroscopy ((31)P-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) (31)P-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 (VO(2max)), 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 VO(2max), 10/16 had elevated resting plasma lactate, and 10/11 that were investigated had impaired citrate synthase-corrected complex I activity. Resting PCr/P(i) ratio and leg P(i) 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 (31)P-MRS variables was as high as 100%, the sensitivity was low (0-63%) and the diagnostic strength of (31)P-MRS was inferior to the other diagnostic tests for MM. Thus, (31)P-MRS should not be a routine test for MM, but may be an important research tool.     

A forearm exercise screening test for mitochondrial myopathy

BACKGROUND: The authors hypothesized that impaired oxygen extraction in mitochondrial myopathy (MM) results in a high oxygen saturation in venous effluent blood from working muscle and that this phenomenon can be used as a diagnostic tool for MM. METHODS: Twelve patients with MM, 10 patients with muscular dystrophy, and 12 healthy subjects were studied. All subjects performed intermittent static handgrip exercise (1/2 Hz) at 40% of maximal voluntary contraction (MVC) for 3 minutes. Cubital venous oxygen saturation and brachial artery flow were measured in the exercised arm. RESULTS: Exercise-induced venous oxygen desaturation was smaller in patients with MM (Delta - 7 +/- 5%) than in subjects with muscular dystrophy (Delta - 38 +/- 2%; p = 0.00001) and healthy subjects (Delta - 43 +/- 2%; p = 0.0000002). MVC and exercise blood flow were similar in patients with MM (18 +/- 3 kg; 436 +/- 65 mL/min) and patients with muscular dystrophy (15 +/- 3 kg; 460 +/- 85 mL/min), but were higher in healthy subjects (32 +/- 4 kg; 630 +/- 58 mL/min; p < 0.03). In seven patients with MM and seven patients with McArdle disease, studied with a slightly different protocol, exercise-induced oxygen desaturation was also impaired in MM (Delta - +/- 5%) compared with McArdle disease (Delta - 26 +/- 3%; p = 0.007). CONCLUSION: Oxygen desaturation in venous blood from exercising muscle is markedly lower in patients with mitochondrial myopathy than in subjects with other muscle diseases and healthy subjects, suggesting that a forearm exercise test can be a diagnostic screening tool for mitochondrial myopathy.     

Lipofuscin accumulation in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease

Exercise-induced oxidative stress has been reported in patients with chronic obstructive pulmonary disease (COPD) and may play a role in muscle fatigue. It is speculated that oxidative stress during exercise originates from the contracting muscles but this has not been documented. The accumulation of lipofuscin, a marker of cellular oxidative damage, was evaluated in the vastus lateralis muscle in 17 patients with COPD and 10 healthy subjects of similar age. Each subject performed a stepwise exercise test up to maximal capacity during which oxygen uptake (VO(2)) was measured. Resting and peak exercise blood gases were also obtained. Two indices of lipofuscin accumulation were used: lipofuscin inclusions/fiber ratio (LI/F) and lipofuscin inclusions/fiber cross-sectional area ratio (LI/CSA). These ratios were also determined for each specific fiber-type. LI/F (P < 0.01) and LI/CSA (P < 0.01) were greater in COPD compared to healthy subjects. LI/F and LI/CSA for all fiber types were also greater in COPD (P < 0.001). In both groups, LI/F (P < 0.001) and LI/CSA (P < 0.01) were higher in type I than in type II fibers. LI/F and LI/CSA did not correlate significantly with resting PaO(2) and SaO(2), peak VO(2), and DeltaPaO(2) and DeltaSaO(2) during exercise (P > 0.05). Increased lipofuscin accumulation, a marker of oxidative damage, was found in the vastus lateralis muscle in patients with COPD compared to healthy subjects. Oxidative damage of muscle tissue may thus be involved in skeletal muscle dysfunction and wasting in COPD.     

Die Spiroergometrie in der Diagnostik mitochondrialer Erkrankungen

Cardiopulmonary exercise testing (CPX) is a non-invasive method of recording quantitative data from gas exchange and ventilation for the evaluation of oxidative metabolism at rest and during exercise. Determination of oxygen uptake (VO2) and carbon dioxide output (VCO2) describes the activity of anaerobic vs aerobic metabolism. An incremental exercise test measuring gas exchange, ventilation and lactate release was performed in healthy volunteers and in patients suffering from mitochondrial disorders. At rest as well as during exercise patients with mitochondrial disorders differ from healthy subjects with regard to gas exchange and ventilation parameters. During exercise, the decreased oxygen utilization of skeletal muscle and early activation of anaerobic metabolism in these patients are mirrored by a reduced anaerobic threshold, reduced maximal oxygen uptake and reduced oxygen pulse. Our study shows that CPX is a sensitive and practical clinical screening method of investigating mitochondrial disorders.     

Brain and skeletal muscle bioenergetic failure in familial hypobetalipoproteinaemia.

OBJECTIVE: To determine whether a multisystemic bioenergetic deficit is an underlying feature of familial hypobetalipoproteinaemia. METHODS: Brain and skeletal muscle bioenergetics were studied by in vivo phosphorus MR spectroscopy (31P-MRS) in two neurologically affected members (mother and son) and in one asymptomatic member (daughter) of a kindred with familial hypobetalipoproteinaemia. Plasma concentrations of vitamin E and coenzyme Q10 (CoQ10) were also assessed. RESULTS: Brain 31P-MRS disclosed in all patients a reduced phosphocreatine (PCr) concentration whereas the calculated ADP concentration was increased. Brain phosphorylation potential was reduced in the members by about 40%. Skeletal muscle was studied at rest in the three members and during aerobic exercise and recovery in the son and daughter. Only the mother showed an impaired mitochondrial function at rest. Both son and daughter showed an increased end exercise ADP concentration whereas the rates of postexercise recovery of PCr and ADP were slow in the daughter. The rate of inorganic phosphate recovery was reduced in both cases. Plasma concentration of vitamin E and CoQ10 was below the normal range in all members. CONCLUSIONS: Structural changes in mitochondrial membranes and deficit of vitamin E together with reduced availability of CoQ10 can be responsible for the multisystemic bioenergetic deficit. Present findings suggest that CoQ10 supplementation may be important in familial hypobetalipoproteinaemia.     

The effects of arm cranking exercise and training on platelet aggregation in male spinal cord individuals

Platelet aggregation at rest and in responses to exercise and training were compared between spinal cord injured (SCI) individuals (N=5) and able-bodied subjects (N=7). All participants performed arm cranking exercise at 60-65% VO(2peak) for 30 min. Venous blood samples were obtained before and after sub-maximal exercise and measured for platelet aggregation using ADP and collagen. To assess the effects of arm cranking training, platelet aggregation was re-measured in all subjects at rest and in response to the sub-maximal arm cranking exercise after 12 weeks of individually supervised training programme. Before training, the resting mean values of platelet aggregation induced by ADP and collagen were not different (P>0.05) between SCI and able-bodied. However the SCI individuals, but not the able-bodied subjects, exhibited a significantly (P<0.05) higher maximal platelet aggregation induced by ADP and collagen following sub-maximal arm cranking exercise. Although VO(2peak) after training was significantly increased (P<0.05) in both groups, the resting mean values of platelet aggregation induced with ADP and collagen were not significantly different (P>0.05) from those observed before training and were not different (P>0.05) between SCI and able-bodied. Post-training, the SCI individuals, but not able-bodied individuals, exhibited a significant decrease (P<0.05) in platelet aggregation following sub-maximal arm cranking exercise and this occurred with both ADP and collagen. These results suggest that SCI individuals, but not normal subjects increase their platelet aggregation following sub-maximal arm cranking exercise. Furthermore, arm cranking training in SCI individuals, appears to diminish the percentage of platelet aggregation ex vivo.     

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 (VO(2max)), workload (W(max)), 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%). VO(2max) and W(max) 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.     

Cycle ergometry is not a sensitive diagnostic test for mitochondrial myopathy

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.     

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 VO(2max). 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.     

Fuel utilization in patients with very long-chain acyl-coa dehydrogenase deficiency

Fuel utilization in two adult patients with the myopathic form of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and five healthy subjects was investigated with stable isotopes during exercise at 50% of VO2max. The findings indicate that residual VLCAD activity in the patients is sufficient to maintain normal oxidation of fat at rest, but that fat oxidation rate cannot increase above basal levels during exercise. This can cause an energy deficit and intramuscular accumulation of fat intermediates that may induce the exercise-induced symptoms.     

Postcontraction depression of reciprocal inhibition in human forearm muscles

We tested whether a preceding muscle contraction changes reciprocal inhibition (RI) between forearm antagonists. RI was studied in 14 healthy subjects by assessing changes in the H reflex (evoked by median-nerve stimulation) in forearm flexor muscles after conditioning radial-nerve stimulation at 0- and 20-ms intervals. The maximum sizes of the M wave (M(max)) and H reflex (H(max)) were also measured. After a long-lasting maximum voluntary handgrip contraction (mean +/- SEM: 3.9 +/- 0.6 min) of ipsilateral forearm muscles, M(max) and H(max) were unchanged but RI was diminished. After contraction of the contralateral homologous muscles and after contraction elicited by ipsilateral muscle stimulation, RI remained unchanged. These results show that a preceding maximum voluntary contraction (lasting 30 s or more) reduces the activity of the spinal inhibitory interneurons mediating RI. This finding may imply the need to reinterpret results from RI studies in normal subjects and in patients with movement disorders.     

Maximal exercise and muscle energy metabolism after recovery from exercise hyperthermia syndrome.

Muscle energy metabolism was studied in 30 subjects after recovery from exercise hyperthermia syndrome (EHTS subjects) and 15 healthy men with identical physical activities. Blood lactate, free fatty acid (FFA), serum creatine kinase activity (CK), and glycerol and the temperature in the auditory duct (T(c)) and on the thumb pad (T(sk)) were measured at rest and during and after maximal exercise on a cycloergometer. The EHTS subjects had a limitation of physical performance, with lowered values for maximal oxygen uptake (VO(2max), P < 0.0005), maximal workload (P < 0.05), and ventilatory threshold (V(t), P < 0.0005). The discrepancy between high plasma concentrations of FFA and the lack of decrease in respiratory ratio (RR) suggests that, in EHTS subjects, a very active release of FFA was not balanced by a proportional increase in catabolism. The increased skin temperature was smaller in EHTS subjects (P < 0.05 at 180 and 200 W). At the end of exercise, auditory duct temperature increase was higher in EHTS subjects than in control subjects (P < 0.05). This study thus showed an impairment of muscle metabolism and an abnormality of thermoregulatory mechanisms. These results may provide insight into the underlying physiopathological disturbance.     

The effects of partial chronic denervation on forearm metabolism.

Effects of chronic denervation upon in vivo forearm metabolism were studied in six patients and six controls. The diagnosis was amyotrophic lateral sclerosis in four patients, the neuronal form of Charcot-Marie Tooth disease in one patient, and an unclassified chronic disease of the lower motor neurons in one patient. In all cases the forearm muscles showed clinical weakness and electrical evidence of denervation, while muscle biopsy from a proximal muscle of the upper limb showed typical denervation atrophy. At rest there was increased oxygen utilization and lactate output as well as a tendency for increased uptake of glucose and long chain fatty acids from arterial blood per 100 ml of forearm tissue. During exercise the abnormally high lactate output increased further. An increased arterial lactate concentration was present during rest and exercise. Oxidation of fatty acids was not impaired. It is suggested that these abnormalities are consistent with an augmented utilization of blood borne fuels at rest by denervated muscles. A concurrent regional ischemia of muscles during rest and exercise, possibly due to defective autoregulation of skeletal muscle blood flow, may explain the abnormally high lactate generation.     

A nonischemic forearm exercise test for McArdle disease

Ischemic forearm exercise invariably causes muscle cramps and pain in patients with glycolytic defects. We investigated an alternative diagnostic exercise test that may be better tolerated. Nine patients with McArdle disease, one with the partial glycolytic defect phosphoglycerate mutase deficiency, and nine matched, healthy subjects performed the classic ischemic forearm protocol and an identical protocol without ischemia. Blood was sampled in the median cubital vein of the exercised arm. Plasma lactate level increased similarly in healthy subjects during ischemic (Delta5.1 +/- 0.7mmol L(-1)) and non-ischemic (Delta4.4 +/- 0.3) tests and decreased similarly in McArdle patients (Delta-0.10 +/- 0.02 vs Delta-0.40 +/- 0.10mmol L(-1)). Postexercise peak lactate to ammonia ratios clearly separated patients and healthy controls in ischemic (McArdle, 4 +/- 2 [range, 1-12]; partial glycolytic defect phosphoglycerate mutase deficiency, 6; healthy, 33 +/- 4 [range, 17-56]) and non-ischemic (McArdle, 5 +/- 1 [range, 1-10]; partial glycolytic defect phosphoglycerate mutase deficiency, 5; healthy, 42 +/- 3 [range, 35-56]) protocols. Similar differences in lactate to ammonia ratio between patients and healthy subjects were observed in two other work protocols using intermittent handgrip contraction at 50% and static handgrip exercise at 30% of maximal voluntary contraction force. All patients developed pain and cramps during the ischemic test, and four had to abort the test prematurely. No patient experienced cramps in the non-ischemic test, and all completed the test. The findings indicate that the diagnostic ischemic forearm test for glycolytic disorders should be replaced by an aerobic forearm test.     

Quantitative near-infrared spectroscopy discriminates between mitochondrial myopathies and normal muscle.

Five patients with chronic progressive external ophthalmoplegia (CPEO) and 27 healthy controls were examined by near-infrared spectroscopy (NIRS) for the noninvasive and direct quantitative measurement of muscle oxygen consumption and forearm blood flow. NIRS measurements were obtained in rest and during static isometric handgrip exercise at 10% of the maximum voluntary contraction (MVC) force. A significantly decreased oxygen consumption at rest as well as during exercise was found in patients with CPEO. Our results suggest that NIRS is able to discriminate between CPEO patients and healthy controls, which makes NIRS a valuable tool in the diagnostic workup of patients suspected to have a mitochondrial myopathy.     

Exercise intensity: platelet function and platelet-leukocyte conjugate formation in untrained subjects

INTRODUCTION: Strenuous and exhaustive exercise intensifies platelet activity as shown in the literature but effects of moderate exercise are still in discussion. The present study investigated effects of two different standardised exercise intensities controlled by individual anaerobic threshold (IAT) on platelet function and conjugate formation. METHODS: 20 healthy male non-smokers underwent two exercises at 80% (moderate) of IAT which corresponded to about 57% of peak oxygen consumption (peak VO(2)) in our subjects and 100% (strenuous) of IAT, corresponding to about 69% peak VO(2). Blood samples were taken after 30 min rest and immediately after exercise. CD62P expression and differentiated platelet-leukocyte conjugates (CD45, CD14, CD41) as well as microparticles and platelet-platelet aggregates were detected flow cytometrically with and without TRAP-6-stimulation. RESULTS: CD62P expression and the number of aggregates were increased (P< or =0.05) after exercise in the TRAP-stimulation experiment independent of exercise intensity. The number of platelet-granulocyte (rest 5.7+/-1.8 to post 8.1+/-1.7 (80%) vs. 6.2+/-1.9 to 10.3+/-2.0 (100%)), platelet-monocyte (5.3+/-3.6 to 8.5+/-3.7 (80%) vs. 7.4+/-3.5 to 11.7+/-4.8 (100%)), and platelet-lymphocyte conjugates (4.4+/-1.2 to 6.4+/-1.3 (80%) vs. 4.6+/-1.7 to 7.8+/-1.8% positive cells (100%)) were also higher after both exercises but increased significantly weaker (P< or =0.05) after moderate exercise. These results were confirmed by the TRAP-stimulation experiment. CONCLUSION: Although moderate exercise led to an increase in platelet reactivity and platelet-leukocyte conjugate formation the changes in conjugate formation were significantly weaker compared to strenuous exercise. Therefore it is recommended that submaximal endurance performance should be individually developed in order for everyone to be able to carry out normal daily activities and also to exercise well below the IAT.     

Physiologic and metabolic response to progressive and prolonged exercise in amyotrophic lateral sclerosis

Physical work capacity in 35 ALS patients and 6 untrained controls was evaluated during progressive bicycle ergometry. In the ALS patients, maximum oxygen consumption (VO2max) and work capacity (Wmax) drop in relation to the decrease in ALS functional score. However, the oxygen cost (ml O2/kpm) of submaximal exercise was significantly increased. Prolonged submaximal exercise tests in six ALS patients and six matched untrained controls indicated that the exercise-induced increase in plasma free fatty acids, beta-hydroxybutyrate, esterified carnitine, and muscle esterified carnitine was significantly retarded in ALS patients.     

Deficit of brain and skeletal muscle bioenergetics in progressive supranuclear palsy shown in vivo by phosphorus magnetic resonance spectroscopy.

Brain and muscle energy metabolism was assessed in vivo in five patients with progressive supranuclear palsy (PSP) using phosphorous magnetic resonance spectroscopy (31P MRS). 31P MRS disclosed a reduced phosphocreatine (PCr) and an increased calculated free adenosine diphosphate (ADP) in the occipital lobes of all patients. In our patients with PSP, inorganic phosphate (Pi) was significantly increased and Mg2+ was reduced. In the gastrocnemius muscle, Pi at rest was increased in four patients, and the three patients who were able to perform an incremental exercise showed a rate of PCr postexercise recovery slower than control subjects. Our findings show that multisystemic deficit of energy metabolism occurs in PSP and suggest that it may play a role in the pathogenesis of this disorder.