Muscle Weakness, Paralysis, and Atrophy after Human Cervical Spinal Cord Injury

Muscle weakness and failure of central motor drive were assessed in triceps brachii muscles of individuals with chronic cervical spinal cord injury (SCI) and able-bodied controls. Electrical stimuli were applied to the radial nerve during rest and during triceps submaximal and maximal voluntary contractions (MVCs). The mean forces and integrated EMGs generated by SCI subjects during MVCs were significantly less than those produced by controls (P < 0.01), with 74 and 71% of muscles generating <10% control force and EMG, respectively. There was an inverse linear relationship between the evoked and voluntary forces (n = 32 muscles of SCI subjects) which, when extrapolated to zero evoked force, also showed significant whole muscle weakness for SCI compared to control subjects (P < 0.01). Severe muscle atrophy was revealed which might reflect disuse and/or muscle denervation subsequent to motoneuron loss. Many triceps muscles of SCI subjects showed no force occlusion (n = 41) or were impossible to stimulate selectively (n = 61). Force was always evoked when the radial nerve was stimulated during MVCs of SCI subjects. The force elicited by single magnetic shocks applied to the motor cortex at Cz′ during voluntary contractions of SCI subjects was also inversely related to the voluntary triceps force exerted (n = 18), but usually no force could be elicited during MVCs. Thus central motor drive was probably maximal to these muscles, and the force evoked during MVCs by below-lesion stimulation must come from activation of paralyzed muscle. SCI subjects also had significantly longer mean central nervous system (CNS) conduction times to triceps (P < 0.01) suggesting that the measured deficits reflect CNS rather than peripheral nervous system factors. Thus, the weak voluntary strength of these partially paralyzed muscles is not due to submaximal excitation of higher CNS centers, but results mainly from reduction of this input to triceps motoneurons.     

Serum brain‐derived neurotrophic factor and interleukin‐6 response to high‐volume mechanically demanding exercise

Introduction: The aim of this study was to follow circulating brain‐derived neurotrophic factor (BDNF) and interleukin‐6 (IL‐6) levels in response to severe muscle‐damaging exercise. Methods: Young healthy men (N = 10) performed a bout of mechanically demanding stretch–shortening cycle exercise consisting of 200 drop jumps. Voluntary and electrically induced knee extension torque, serum BDNF levels, and IL‐6 levels were measured before and for up to 7 days after exercise. Results: Muscle force decreased by up to 40% and did not recover by 24 hours after exercise. Serum BDNF was decreased 1 hour and 24 hours after exercise, whereas IL‐6 increased immediately and 1 hour after but recovered to baseline by 24 hours after exercise. IL‐6 and 100‐Hz stimulation torque were correlated (r = ?0.64, P < 0.05) 24 hours after exercise. Discussion: In response to acute, severe muscle‐damaging exercise, serum BDNF levels decrease, whereas IL‐6 levels increase and are associated with peripheral fatigue. Muscle Nerve 57 : E46–E51, 2018     

The Effect of Fatigue on the Timing of Electrical Stimulation‐Evoked Muscle Contractions in People with Spinal Cord Injury

This study investigated the activation dynamics of electrical stimulation‐evoked muscle contractions performed by individuals with spinal cord injury (SCI). The purpose was to determine whether electrical stimulation (ES) firing patterns during cycling exercise should be altered in response to fatigue‐induced changes in the time taken for force to rise and fall with ES. Seven individuals with SCI performed isometric contractions and pedaled a motorized cycle ergometer with stimulation applied to the quadriceps muscles. Both exercise conditions were performed for five minutes while the patterns of torque production were recorded. ES‐evoked knee extension torque fell by 75% under isometric conditions, and the rate of force rise and decline decreased in proportion to torque (r = 0.91, r = 0.94, respectively). There was no change in the time for torque to rise to 50% of maximum levels. The time for torque to decline did increase slightly, but only during the first minute of exercise. Cycling power output fell approximately 50% during the five minutes of exercise, however, there was no change in the time taken for torque to rise or fall. The magnitude of ES‐evoked muscle torques decline substantially with fatigue, however, the overall pattern of torque production remained relatively unchanged. These results suggest there is no need to alter stimulation firing patterns to accommodate fatigue during ES‐evoked exercise.     

Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome

OBJECTIVES—To examine the proportions of type 1 and type 2 muscle fibres and the degree of muscle fibre atrophy andhypertrophy in patients with chronic fatigue syndrome in relation tolactate responses to exercise, and to determine to what extent anyabnormalities found might be due to inactivity.
METHODS—Quadriceps needle muscle biopsies wereobtained from 105 patients with chronic fatigue syndrome and theproportions of type 1 and 2 fibres and fibre atrophy and hypertrophyfactors were determined from histochemical preparations, using asemiautomated image analysis system. Forty one randomly selectedbiopsies were also examined by electron microscopy. Lactate responsesto exercise were measured in the subanaerobic threshold exercise test (SATET).
RESULTS—Inactivity would be expected to result ina shift to type 2 fibre predominance and fibre atrophy, but type 1 predominance (23%) was more common than type 2 predominance (3%), andfibre atrophy was found in only 10.4% of cases. Patients withincreased lactate responses to exercise did have significantly fewertype 1 muscle fibres (p<0.043 males, p<0.0003 females), but there was no evidence that this group was less active than the patients withnormal lactate responses. No significant ultrastructural abnormalitieswere found.
CONCLUSION—Muscle histometry in patients withchronic fatigue syndrome generally did not show the changes expected asa result of inactivity. However, patients with abnormal lactateresponses to exercise had a significantly lower proportion ofmitochondria rich type 1 muscle fibres.

     

Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome

Patients with the chronic fatigue syndrome (CFS) complain consistently of delay in recovery of peripheral muscle function after exercise. The purpose of this study was to try to confirm this observation. A fatiguing exercise test was carried out on the quadriceps muscle group of ten patients and ten control subjects. The test consisted of 18 maximum voluntary contractions (MVCs) with a 50% duty cycle (10 s contraction, 10 s rest), and the force generated by each contraction was recorded using a KinCom dynamometer. This was followed by a recovery phase lasting 200 min in which quadriceps strength was evaluated at increasing intervals, and a follow-up session at 24 h post-exercise involving three 10 s MVCs. Throughout the exercise period, the MVCs obtained from the control group were significantly higher than those of the patient group (P = 0.006), but both groups showed a parallel decline in force over the 18 contractions, in keeping with a similar endurance capacity. Recovery was prolonged in the patient group, however, with a significant difference compared to initial MVCs being evident during the recovery phase after exercise (P = 0.001) and also at 24 h (P < 0.001). In contrast, the control group achieved MVCs which were not significantly different from initial values during the recovery phase, and maintained these at 24 h. These findings support the clinical complaint of delayed recovery after exercise in patients with CFS.     

The effects of strength,aerobic, and concurrent exercise on skeletal muscle damage in rats

Introduction: In this study we examined oxidative stress and skeletal muscle damage resulting from acute strength, aerobic, or concurrent exercise in rats. Methods: The animals were divided into control (C), strength (SE), aerobic (AE), and combined (CE) exercise groups. They were euthanized at 3 different time‐points (6, 24, and 48 h) after acute exercise. Results: SE exercise rats had increased dichlorofluorescein oxidation at 6 h post‐exercise and decreased superoxide dismutase activity at all time‐points. Glutathione peroxidase activity and sulfhydryl levels were increased in the AE group at 48 h post‐exercise. Serum lactate dehydrogenase activity was increased in the SE and CE groups at 24 h and in the AE group at 48 h. Echo intensity was elevated at 24 h for all groups. Conclusions: Forty‐eight hours was sufficient for complete recovery from oxidative stress and muscle damage in the SE and CE groups, but not in the AE group. Muscle Nerve 50 : 79–86, 2014     

Association of muscle strength and electrophysiological measures of reinnervation in diabetic neuropathy

Motor function was assessed in 34 non-insulin-dependent and 19 insulin-dependent diabetic patients with macroelectromyography and isokinetic dynamometry. Fiber density (FD) and the amplitude of the macro motor unit potential (macro MUP) of the anterior tibial and lateral vastus muscles were obtained and maximal isokinetic strength of the ankle and knee extensors were determined. All patients underwent standardized clinical examination including a neurological disability score (NDS), quantitative sensory examination, and conventional motor nerve conduction studies. The amplitude of the macro MUP and FD of the anterior tibial muscle were increased in neuropathic patients without weakness (P < 0.05) and further increased in neuropathic patients with weakness (P < 0.05). The NDS was related to the FD and the amplitude of the macro MUP for the anterior tibial and lateral vastus muscle [r = 0.55–0.75 (P < 0.005)]. Muscle strength of ankle and knee extensors correlated with the FD [r = −0.69 (P < 0.0001) and r = −0.58 (P < 0.001), respectively] and with the amplitude of the macro MUP of the two muscles [r = −0.63 (P < 0.0001) and r = −0.37 (P < 0.05), respectively]. Our findings support the hypothesis that loss of muscle strength in diabetic patients is due to incomplete reinnervation following axonal loss. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1647–1654, 1998     

Muscle activation varies with contraction mode in human spinal cord injury

Introduction: To better understand volitional force generation after chronic incomplete spinal cord injury (SCI), we examined muscle activation during single and repeated isometric, concentric, and eccentric knee extensor (KE) maximal voluntary contractions (MVCs). Methods: Torque and electromyographic (EMG) activity were recorded during single and repeated isometric and dynamic KE MVCs in 11 SCI subjects. Central activation ratios (CARs) were calculated for all contraction modes in SCI subjects and 11 healthy controls. Results: SCI subjects generated greater torque, KE EMG, and CARs during single eccentric vs. isometric and concentric MVCs (all P < 0.05). Torque and EMG remained similar during repeated eccentric MVCs; however, both increased during repeated isometric (>25%) and concentric (>30%) MVCs. Conclusions: SCI subjects demonstrated greater muscle activation during eccentric MVCs vs. isometric and concentric MVCs. This pattern of activation contrasts with the decreased eccentric activation demonstrated by healthy controls. Such information may aid development of novel rehabilitation interventions. Muscle Nerve 51 : 235–245, 2015     

Altered corticospinal transmission to the hand after maximum voluntary efforts

Introduction: After maximal voluntary contractions (MVCs), responses to corticospinal tract stimulation change differently in arm and leg muscles. This study we examined responses in the first dorsal interosseous muscle (FDI). Methods: Stimulation of the corticospinal tract at the cervicomedullary motor evoked potentials in FDI. Stimuli were delivered before and after 10‐s and 1‐min MVCs. The reproducibility of changes in the cervicomedullary motor evoked potentials (CMEPs) was investigated. F‐waves tested motoneuron excitability. Results: After the MVCs, the CMEP area was initially variable. By ∽1 min after 10‐s and 1‐min MVCs, CMEPs in relaxed muscle decreased to 63 ± 15% and 52 ± 32%, respectively, of control and remained depressed for ∽10 min. Responses evoked 2 days apart varied between subjects but not between days. After 10‐s MVCs, F‐waves were reduced at rest. During weak contraction, CMEPs but not F‐waves were depressed. Conclusions: Our results suggest that contraction produces changes at the corticomotoneuronal synapses to FDI. In addition, motoneuron excitability is reduced. Muscle Nerve, 2011     

Cerebral Glutamine Concentration and Lactate–Pyruvate Ratio in Patients with Acute Liver Failure

Aim  Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate–pyruvate ratio is associated with a rise in the glutamine concentration and ICP. Patients and Methods  In 13 patients with ALF (8F/5M; median age 46 (range 18–66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion pressure (CPP). Results  The cerebral glutamine concentration was 4,396 (1,011–9,712) μM, lactate 2.15 (1.1–4.45) mM, and pyruvate 101 (43–255) μM. The lactate–pyruvate ratio was 21 (16–40), ICP 20 (2–28) mmHg, and CPP 72 (56–115) mmHg. Cerebral glutamine concentration correlated with the lactate–pyruvate ratio (r = 0.89, P < 0.05). Also the ICP, but not CPP, correlated to the lactate–pyruvate ratio (r = 0.64, P < 0.05). Conclusion  ICP and the cerebral glutamine concentration in patients with ALF correlate to the lactate–pyruvate ratio. Since CPP was sufficient in all patients the rise in lactate–pyruvate ratio indicates that accumulation of glutamine compromises mitochondrial function and causes intracranial hypertension.     

Lipid peroxides production after strenuous exercise and in relation to muscle morphology and capillarization

The antioxidative capacity of slow twitch muscle fibers has been reported to be higher than that of fast twitch ones. The purpose of this study was to relate the production of lipid peroxides during exercise to the morphology and capillarization of human muscles. Twenty-seven healthy volunteers performed a strenuous 90-min exercise. The content of malonyldialdehyde (MDA) in the middle portion of vastus lateralis muscle was found positively correlated with percentage and the relative cross-sectional area of the type I of muscle fibers (r = 0.46, P < 0.05, r = 0.43, P < 0.05, respectively) but negatively with type II muscle fibers (r = -0.46, P < 0.05, r = -0.43, P < 0.05, respectively), especially type IIB. The content of MDA in the vastus lateralis muscle correlated positively with the number of capillaries around type II muscle fibers (r = 0.71, P < 0.001). It is suggested that the production of lipid peroxides parallels the exercise-induced increase of oxygen uptake in the muscle, being highest in more oxidative and better perfused, oxygen-consuming muscle fibers. © 1996 John Wiley & Sons, Inc.     

Muscle fatigue during intermittent exercise in individuals with mental retardation

This study examined fatigue profile during intermittent exercise in 10 men with mild to moderate mental retardation (MR) and 10 men without mental retardation (C). They performed 4 × 30 s maximal knee extensions and flexions with 1-min rest on an isokinetic dynamometer. Peak torque of flexors (PTFL) and extensors (PTEX), total work (TW), and lactate were measured. Fatigue was calculated as the magnitude of decline (%) in PTFL, PTEX, and TW and as rate of decline (linear slope) in TW from 1st to 4th set. MR had lower PTFL, PTEX, TW, and lactate throughout the protocol than C, while pre-motor time was greater in MR vs. C (p < 0.05). MR demonstrated a delayed pattern of reduction in muscular performance. Lower values were observed in MR vs. C in the magnitude of decline for PTEX and TW and the rate of decline for TW. In conclusion, MR exhibit a different fatigue profile during intermittent exercise than C. The lower magnitude and decline rate in neuromuscular performance in MR during intermittent exercise is associated with their lower peak strength, short-term anaerobic capacity, and lactate accumulation. Rehabilitation and sport professionals should consider the differences in fatigue profile when designing intermittent exercise programs for MR.     

Muscle membrane polarisation after provocative tests, and after cooling: the normal CMAP changes to be expected.

OBJECTIVE: To know the range of changes of compound muscle action potentials (CMAPs) in the muscles innervated by the ulnar nerve after diverse provocative tests, 14 healthy patients were studied with the same protocol. METHODS: CMAPs were measured at rest, just after a short exercise test (SET), during short 5 and 10c/s repetitive nerve stimulation (RNS) trains, at approximately 32 and approximately 20 degrees C. RESULTS: At 32 degrees C, the SET induced a significant but transient enlargement of the CMAPs (amplitude increased by 8.3%, duration decreased by 9%) that was only partially reproduced by RNS trains, except for a significant shortening of the CMAPs at 10c/s. At 20 degrees C without exercise, CMAPs increased significantly by approximately 30% in amplitude, duration and area, and after the SET the inverse of what has been seen at 32 degrees C was observed (amplitude decreased by 1.7% and duration increased by 9%). RNS at 20 degrees C produced a marked interpatient heterogeneity except for a significant shortening of the CMAPs at 10c/s. In one pure autonomic failure patient, the infusion of norepinephrine induced potentiation of the responses at rest and a decrease in the expected changes after provocative tests. CONCLUSIONS: CMAP amplitude and duration are significantly modified just after the SET at 32 degrees C, at rest at 20 degrees C and after RNS at 10c/s but not at 5c/s. Although providing indirect evidence, these findings indicate that provocative tests make the muscle membrane hyperexcitable by the way of a direct influence on the electrical events and by an indirect local catecholamine spillover.     

Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle

Corticosteroid myopathy is a major clinical problem in patients undergoing chronic corticosteroid treatment and shows insidious and progressive muscle atrophy in proximal limbs. Although several mechanisms underlying the pathophysiology of muscle injury have been postulated, precise pathogenesis is still not clear. We evaluated the mitochondrial functions in patients receiving corticosteroids compared with those in healthy controls or patients not receiving corticosteroids. The serum levels and total production of lactate were investigated by an aerobic exercise test using a bicycle ergometer. Mitochondrial respiratory activities and oxidative damage in biopsied skeletal muscles were also studied. The results of aerobic exercise tests revealed a significant overproduction of lactate in patients treated with corticosteroids (p < 0.005), which was positively correlated with total corticosteroid doses administered (p < 0.0001). In these patients, mitochondrial enzyme activity in complex I was significantly decreased (p < 0.05) and oxidative damage of biopsied skeletal muscle was remarkable both in mitochondrial and nuclear DNAs (p < 0.001). The results suggest that chronic corticosteroid administration induces mitochondrial dysfunction and oxidative damage in skeletal muscles, which may be the pathogenesis, at least in part, of corticosteroid-induced myopathy. Received: 5 November 2001 Received in revised form: 4 February 2002 Accepted: 7 February 2002     

ATP, phosphocreatine and lactate in exercising muscle in mitochondrial disease and McArdle's disease

We studied exercise-induced changes in the adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels in the skeletal muscle of mitochondrial patients and patients with McArdle's disease. Needle muscle biopsy specimens for biochemical measurement were obtained before and immediately after maximal short-term bicycle exercise test from 12 patients suffering from autosomal dominant and recessive forms of progressive external ophthalmoplegia and multiple deletions of mitochondrial DNA (adPEO, arPEO, respectively), five patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3243 A-->G point mutation, and four patients with McArdle's disease. Muscle ATP and PCr levels at rest or after exercise did not differ significantly from those of the controls in any patient group. In patients with mitochondrial disease, muscle lactate tended to be lower at rest and increase more during exercise than in controls, the most remarkable rise being measured in patients with adPEO with generalized muscle symptoms and in patients with MELAS point mutation. In McArdle patients, the muscle lactate level decreased during exercise. No correlation was found between the muscle ATP and PCr levels and the respiratory chain enzyme activity.     

Cerebrospinal fluid lactate and pyruvate concentrations in patients with malignant hypertension

Summary Lactate and pyruvate concentrations and acid-base parameters in cerebrospinal fluid (CSF) and arterial blood were measured in 21 patients with malignant hypertension (MHT), 19 with benign hypertension (BHT) and 21 normotensive subjects (NT). Average values for CSF lactate and lactate/pyruvate (L/P) ratio were significantly higher in MHT (1.90±10mM/1, 19.2±1.0) than in either BHT (1.50±0.05 mM/1, 15.7±0.7) or NT (1.44±0.04 mM/1, 15.7±0.4). There was a linear correlation between CSF lactate and CSF pressure (r=0.565, P<0.01), and the latter was also related to mean arterial pressure exceeding 150 mm Hg (r=0.553, P<0.01). Such increases in the acid metabolites in CSF indicate that brain metabolism becomes anaerobic in MHT, probably due to increased intracranial prssure. Increased cerebrovascular permeability is also discussed as participating in causal mechanisms.

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Zusammenfassung Bei 21 Patienten mit maligner Hypertonie, 19 mit benigner Hypertonie und 21 mit normalem Blutdruck wurden in Blut und Liquor die Lactat- und Pyruvatkonzentrationen sowie die Säure-Basen-Parameter gemessen. Die Werte für das Lactat bzw. für das Lactat-Pyruvat-Verhältnis im Liquor waren bei Patienten mit maligner Hypertonie signifikant höher (1,90±0,10 mM/1, 19,2±1,0) als bei den Patienten mit benigner Hypertonie (1,50±0,05 mM/1, 15,7±0,7) bzw. bei normotensiven Individuen (1,44±0,04 mM/1, 15,7±0,4). Es bestand eine lineare Korrelation zwischen den Lactatwerten und dem Druck im Liquor (r=0,565, P<0,01), wobei dies außerdem korrelierte mit einem mittleren arteriellen Blutdruck von mehr als 150 mm Hg (r=0,553, P<0,01). Diese Zunahme in den Säuremetaboliten im Liquor weist darauf hin, daß der Hirnstoffwechsel bei maligner Hypertonie in eine anaerobe Phase tritt, wahrscheinlich wegen des erhöhten intrakraniellen Druckes. Es wird auch die Möglichkeit einer erhöhten cerebralen Gefäßdurchlässigkeit als mitbeteiligter Mechanismus erwogen.

     

Impaired sympathetic neural recruitment during exercise pressor reflex activation in women with post-traumatic stress disorder

Muscle sympathetic nerve activity (MSNA) increases during isometric exercise via increased firing of low-threshold action potentials (AP), recruitment of larger, higher-threshold APs, and synaptic delay modifications. Recent work found that women with post-traumatic stress disorder (PTSD) demonstrate exaggerated early-onset MSNA responses to exercise; however, it is unclear how PTSD affects AP recruitment patterns during fatiguing exercise. We hypothesized that women with PTSD (n?=?11, 43 [11] [SD] years) would exhibit exaggerated sympathetic neural recruitment compared to women without PTSD (controls; n?=?13, 40 [8] years). MSNA and AP discharge patterns (via microneurography and a continuous wavelet transform) were measured during 1 min of baseline, isometric handgrip exercise (IHG) to fatigue, 2 min of post-exercise circulatory occlusion (PECO), and 3 min of recovery. Women with PTSD were unable to increase AP content per burst compared to controls throughout IHG and PECO (main effect of group: P?=?0.026). Furthermore, relative to controls, women with PTSD recruited fewer AP clusters per burst during the first (controls: ?1.3 [1.2] vs. PTSD: ??0.2 [0.8]; P?=?0.016) and second minute (controls: ?1.2 [1.1] vs. PTSD: ??0.1 [0.8]; P?=?0.022) of PECO, and fewer subpopulations of larger, previously silent axons during the first (controls: ?5 [4] vs. PTSD: ?1 [2]; P?=?0.020) and second minute (controls: ?4 [2] vs. PTSD: ?1 [2]; P?=?0.021) of PECO. Conversely, PTSD did not modify the AP cluster size–latency relationship during baseline, the end of IHG, or PECO (all P?=?0.658–0.745). Collectively, these data indicate that women with PTSD demonstrate inherent impairments in the fundamental neural coding patterns elicited by the sympathetic nervous system during IHG and exercise pressor reflex activation.

     

The associations of adiposity, physical activity and inflammation with fatigue in older adults

Persistent feelings of fatigue are a widespread complaint reported by older adults, and are associated with detriments in health and quality of life. The aim of this study was to determine the influence of weight status, habitual physical activity and inflammation, after controlling for common psychosocial variables such as depression, on perceptions of fatigue in relatively healthy older adults. Older men and women (N = 182, age = 69.2 ± 6.7 years, 98 men) were assessed for adiposity via dual-energy X-ray absorptiometry, physical activity (PA) using accelerometers, systemic inflammation [serum C-reactive protein (CRP), interleukin-6 (IL-6), sIL-6R and WBC count], fatigue according to the Multidimensional Fatigue Inventory (MFI), sleep using the Pittsburgh Sleep Quality Index (PSQI) and depression via the Geriatric Depression Scale (GDS). Men and women reported similar levels of fatigue in all dimensions (p > 0.05) except women reported higher levels of mental fatigue than men (p = 0.049). With the exception of mental fatigue, adiposity was positively, and physical activity was inversely associated with all other dimension of fatigue (r range = 0.20–0.42, and −0.18 to −0.37, respectively). CRP, IL-6 and WBC were also related to several dimensions of fatigue (r range = 0.15–0.26). Regression analyses revealed that after controlling for other factors, including depression and sleep quality, adiposity independently explained a significant amount of the variance in general and physical fatigue. In addition to depression and sleep quality, adiposity may represent a potential target for reducing fatigue in older adults.     

Response of serum enzymes and other biochemical constituents to strenuous exercise in control subjects and patients with motor neurone disease

Serum enzymes were estimated in 10 patients with motor neurone disease (MND) and in 5 control subjects at rest and after strenuous exercise. Creatine phosphokinase (CPK) levels were abnormally increased at rest in 6 of the MND patients, 1 of whom had the only abnormal increase in resting level of malate dehydrogenase (MDH). MDH and CPK increased, sometimes to abnormal levels, in response to exercise in control subjects. The mean rise in MDH after exercise in the MND patients closely paralleled that of the control group. In spite of higher resting CPK levels in MND patients compared to controls, the percentage increase in CPK activity immediately after exercise in this group was significantly lower than for controls. No significant changes in aspartate aminotransferase (GOT), sodium, total protein or urea were observed in either group before or after exercise, but significant differences were noted in the response patterns of potassium and bicarbonate.We suggest that abnormal resting CPK activities recorded in MND patients are caused by near maximal efflux from actively necrotic muscle cells, and any superimposed rise in CPK levels after exercise may be contributed by enzyme efflux from the remaining normal muscle cell mass.     

A mitochondrial encephalomyopathy with a partial cytochrome c oxidase deficiency of muscle.

A 16 year old girl showed delayed psychomotor development. In infancy, exercise intolerance, cerebellar signs, deteriorated with increasing intercurrent infections, and disturbances of breathing and cardiac rhythm became manifest. From the age of 7 years there was chronic progressive psychomotor deterioration, with hypotonia, a bilateral pyramidal and cerebellar syndrome, and mild epilepsy. CSF pyruvate and lactate levels were elevated, and lactate content was elevated in the urine. There was an abnormally high rise of lactate levels on moderate exercise and an abnormal response to pyruvate loading. Quadriceps muscle biopsies obtained at age 10 and 16 years showed ragged-red fibres, and a decreased cytochrome c oxidase activity and cytochrome aa3 content. Cytochrome c oxidase activity in fibroblasts was normal. Clinical signs and symptoms in association with a disturbance of mitochondrial energy metabolism led us to diagnosis of probable Leigh syndrome.