Impaired oxygen utilization in skeletal muscle of CRPS I patients.

BACKGROUND: The purpose of this study was to evaluate oxygen extraction and utilization in end stage chronic complex regional pain syndrome type I (CRPS I) patients undergoing amputation and to relate these to muscle histology of the amputated limb. MATERIALS AND METHODS: In 25 patients with severe CRPS I requiring amputation of the affected limb venous blood samples and in 11 patients skeletal muscle specimens were analyzed. RESULTS: The mean venous oxygen saturation (S(v)O(2)) value (94.3% ± 4.0%) of the affected limb was significantly higher than S(v)O(2) values found in healthy subjects (77.5% ± 9.8%) pointing to a severely decreased oxygen diffusion or utilization within the affected limb. Histologic analysis showed a significant decrease of type I fibers and a significant increase of type IIB fibers. Ultrastructural investigations of soleus skeletal muscle capillaries revealed thickened endothelial cells and thickened basement membranes. Muscle capillary densities were decreased in comparison with literature data. High venous oxygen saturation levels were partially explained by impaired diffusion of oxygen due to thickened basement membrane and decreased capillary density. CONCLUSION: This study shows that venous oxygen saturation is significantly increased in chronic end stage CRPS I patients corresponding with impaired oxygen diffusion. The abnormal skeletal muscle findings points to severe disuse but only partially explain the impaired diffusion of oxygen; mitochondrial dysfunction seems a likely explanation in addition.

The oxidative response in the chronic constriction injury model of neuropathic pain.

BACKGROUND: In the chronic constriction injury model of rat neuropathic pain, oxidative stress as well as antioxidants superoxide dismutase and reduced glutathione (GSH) are important determinants of neuropathological and behavioral consequences. Studies of the chronic constriction injury model observed (indirect) signs of inflammation. We, therefore, investigated the level of oxidative stress and antioxidant enzymes in skeletal muscle tissue of the rat hind paw and (jugular vein) plasma at d 7 after nerve injury. MATERIALS AND METHODS: The level of reactive oxygen and nitrogen species (RONS) was determined as a measure of oxidative stress. Reduced GSH levels and the ceruloplasmin/transferrin ratio were determined as measures of overall antioxidant activity. RONS and overall antioxidant activity were measured in skeletal muscle tissue of the hind paw and jugular vein plasma. The level of RONS in muscle was determined using spin trapping combined with electron paramagnetic resonance spectroscopy. Using electron paramagnetic resonance spectroscopy, we also determined plasma levels of transferrin and ceruloplasmin. GSH levels were determined using high-performance liquid chromatography. RESULTS: In skeletal muscle tissue, the level of RONS was lower in nerve-injured hind paws than in controls. The plasma level (jugular vein) of RONS did not differ between nerve-injured and control rats. In skeletal muscle tissue, the level of GSH was higher in nerve-injured hind paws than in controls. The ceruloplasmin/transferrin ratio tended to be higher in (jugular vein) plasma of nerve-injured rats as compared to controls. CONCLUSIONS: This study shows that, at d 7 after nerve injury, oxidative stress-induced changes are present also in skeletal muscle tissue of the rat hind paw. Our findings of a decreased level of RONS in combination with an increased level of the antioxidant GSH suggest that an overshoot of antioxidant activity overrules initial oxidative stress.

Early diagnosis of ALS: the search for signs of denervation in clinically normal muscles.

AIM AND METHODS: We prospectively investigated whether early diagnosis of amyotrophic lateral sclerosis (ALS) could be facilitated by demonstrating signs of denervation in a muscle of a clinical and electromyographical unaffected region. Muscle fibre conduction velocity (MFCV) was determined in 18 patients in whom the diagnosis ALS was considered but not established beyond a level of clinically possible ALS according to the revised El Escorial criteria. A muscle biopsy was obtained from the same muscle, to demonstrate neurogenic changes. The study followed the guidelines from the STARD initiative. RESULTS AND CONCLUSION: Results were analysed with respect to the final diagnosis. After a mean follow-up of 16 months, 9 patients developed probable or definite ALS. Sensitivity of abnormal MFCV for developing ALS was 89%. Muscle biopsy confirmed that denervation was the cause of abnormal MFCV. We concluded that MFCV can be used to detect denervation in muscles that show no clinical or electromyographical signs of lower motor neuron disease, and thus may contribute to early diagnosis of probable laboratory-supported ALS.

Novel mutations in three patients with LGMD2C with phenotypic differences.

Limb-girdle muscular dystrophy type 2C is an autosomal-recessive disorder caused by mutations in gamma-sarcoglycan encoding gene. This disease is characterized by childhood onset of progressive muscular dystrophy. Because of the clinical presentation, this disorder may be misdiagnosed as a dystrophinopathy. Two males (Patients A and B) from one Turkish family and one male (Patient C) from a Moroccan family had progressive walking disturbances for several years, exercise intolerance, and leg pains. Clinical examination revealed limb-girdle weakness and calf hypertrophy. Serum creatine kinase levels ranged from 1100 to 19000 U/L. The initial findings and course of the disease were less severe in Patient B compared with his brother (Patient A) at the same age. By means of immunohistochemistry on muscle biopsy all patients manifested reduced expression of alpha-, beta-, gamma-, and delta-sarcoglycans. DNA sequence analysis revealed a homozygous splice site mutation in exon 5 (IVS5+2T>C) in the Turkish family. In the patient from the Moroccan family a homozygous nonsense mutation in exon 2 (93G>A;Trp31X) was present. In conclusion, this report describes the clinical, histologic, and immunohistochemical characteristics of three children with limb-girdle muscular dystrophy type 2C. Two novel mutations in the gamma-sarcoglycan gene were present. We found phenotypic differences in two brothers.

Concomitant dermatomyositis and myasthenia gravis presenting with respiratory insufficiency.

We report a 28-year-old woman with a history of chronic immune-mediated hepatitis, in whom the simultaneous manifestation of dermatomyositis and myasthenia gravis resulted in severe neck extensor weakness and subacute respiratory insufficiency, followed by proximal muscle weakness and external ophthalmoplegia. Radiological signs of a thymoma were absent. The distinguishing clinical, electrophysiological, and biopsy findings are discussed. We suggest that an underlying immunoregulatory disorder was present, explaining the occurrence of three rare immune-mediated diseases in one patient.

Muscle-fiber conduction velocity and electromyography as diagnostic tools in patients with suspected inflammatory myopathy: a prospective study.

Combinations of different techniques can increase the diagnostic yield from neurophysiological examination of muscle. In 25 patients with suspected inflammatory myopathy, we prospectively performed needle electromyography (EMG) and measured muscle-fiber conduction velocity (MFCV) in a single muscle, using a technique with direct muscle-fiber stimulation and recording. Results of MFCV were compared with final diagnosis, EMG, and needle muscle biopsy. Diagnostic accuracy of combined MFCV and EMG studies was 72%, compared to 60% for EMG alone. This improvement was due to a gain in specificity. The MFCV did not prove useful in discriminating inflammatory myopathy from other myopathies. Furthermore, we found a correlation of 92% between variability of MFCV and myopathic changes in muscle biopsy. We conclude that the utility of electrodiagnostic examination can be increased if EMG examination is combined with MFCV studies.