For patients in Norway with LGG, treatment at a center that favored early surgical resection was associated with better overall survival than treatment at a center that favored biopsy and watchful waiting. This survival benefit remained after adjusting for validated prognostic factors.

Normal means and ranges for the density of epidermal nerve fibers in a reference population have been established. The density of epidermal nerve fibers decreases with age and is lower in men compared with women. Intraobserver and interobserver analysis proves the reliability of the method.

Mitochondrial dysfunction reduces aerobic energy production and results in symptoms from various tissues, depending on metabolic demands. Mitochondrial adenosine triphosphate (ATP) is essential for sperm motility. Sperm motility was investigated in a patient with a mitochondrial disease caused by reduced activity of the mitochondrial enzyme complexes I and IV, and in two control subjects. Spermatozoa were cultured in media containing various energy substrates. Motility was judged by light microscopy, and ultrastructure by transmission electron microscopy. In the patient with mitochondrial disease, 12% of the spermatozoa were motile in the medium containing only glucose. There was a three-fold increase in motile spermatozoa when pyruvate and succinate were present together with glucose. In contrast, the spermatozoa of both control subjects had best motility in the presence of substrates for complex I, and no further increase was observed when succinate was added. Glucose and pyruvate enter the respiratory chain at complex I, and succinate at complex II. Electron microscopy of spermatozoa from the patient with mitochondrial disease revealed mitochondria with increased matrix, thickening of membranes, parallelization of cristae and lipid inclusions, which are characteristic findings in mitochondrial disorders. Abnormal mitochondria were also found in a spermatid, suggesting that the ultrastructural changes of mitochondria are primary rather than secondary to degeneration of the spermatozoa. The results indicate that mitochondrial dysfunction causes reduced sperm motility in some men.

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To obtain normative muscle morphology data on a healthy population recruited from a population survey, we examined vastus lateralis biopsies from 58 men and 33 women, aged 26-67 years. Biopsies were measured with automated, computer-aided techniques. Data were analyzed according to gender and age, and the influence of blood pressure, body mass index (BMI), and smoking habits was also examined. Men had larger muscle fibers (fiber area approximately 5400 microm(2)) than women ( approximately 4000 microm(2), P = 0.003). No gender differences were seen in fiber composition, fiber roundness, percentage of connective tissue, or capillary density. Blood pressure did not influence fiber size or composition, but was correlated with fiber roundness in men. BMI was associated with fiber area in men, but not in women. Variations in age, smoking habits, and physical activity did not influence muscle morphology data substantially. Thus, in a normal population, men have larger muscle fibers than women, but similar fiber composition. Variation in gender, BMI, blood pressure, and physical activity may influence morphological features to a minor degree.

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are a common cause of inherited neuromuscular disorders and have been associated with a wide clinical spectrum, ranging from various congenital myopathies to the malignant hyperthermia susceptibility (MHS) trait without any associated weakness. RYR1-related myopathies are usually of early-childhood onset. Here we present 11 patients from 8 families with a late-onset axial myopathy associated with RYR1 variants. Patients presented between the third and seventh decade of life to neuromuscular centres in Norway, the Netherlands and the United Kingdom with predominant axial muscle involvement, comprising variable degrees of lumbar hyperlordosis, scapular winging and/or camptocormia. Marked myalgia was commonly associated. Serum creatine kinase levels were normal or moderately elevated. Muscle imaging showed consistent involvement of the lower paravertebral muscles and the posterior thigh. Muscle biopsy findings were often discrete, featuring variability in fibre size, increased internal nuclei and unevenness of oxidative enzyme staining, but only rarely overt cores. RYR1 sequencing revealed heterozygous missense variants, either previously associated with the MHS trait or localizing to known MHS mutational hotspots. These findings indicate that MHS-related RYR1 mutations may present later in life with prominent axial weakness but not always typical histopathological features. We propose a combined effect of RyR1 dysfunction, aging and particular vulnerability of axial muscle groups as a possible pathogenic mechanism. RYR1 is a candidate for cases with "idiopathic" camptocormia or bent spine syndrome (BSS).

Small diameter nerve fibre (SDNF) neuropathy is an axonal sensory neuropathy affecting unmyelinated (C) and thin myelinated (A-delta) fibres. We have evaluated 75 patients with symptoms and signs suggesting SDNF dysfunction with or without symptoms and signs of co-existing large diameter nerve fibre involvement. The patients were examined clinically and underwent skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS). The purpose of this study was to compare the relationship between the different methods and in particular measurements of thermal thresholds and intraepidermal nerve fibre (IENF) density in the same site of the distal leg. The main subdivision of the patient material was made according to the overall NCS pattern. Patients with normal NCS (38) had 6.4 +/- 3.8 and patients with abnormal NCS (37) had 4.4 +/- 3.4 IENF per mm (P = 0.02). Limen (difference between warm and cold perception thresholds) was significantly higher (more abnormal) in those with abnormal than in those with normal NCS (22.1 +/- 9.1 vs. 13.4 +/- 5.6, P < 0.0001). Cold perception threshold was more abnormal (P < 0.0001) than warm perception threshold (P = 0.002). Correlation between IENF and QST was statistically significant only when NCS was abnormal, and thus dependent of a more severe neuropathic process in SDNFs.