Long-term variability and reproducibility of resting human muscle nerve sympathetic activity at rest,as reassessed after a decade

Human muscle nerve sympathetic activity measured by microneurography during supine rest is known to vary considerably between healthy subjects, whereas in a given individual the level of muscle nerve sympathetic activity is stable over weeks and months. To further characterize long-term variability or reproducibility microneurographic recordings of muscle nerve sympathetic activity were performed in 15 healthy, normotensive subjects (mean age 51 years) who had undergone the same procedure between 10 and 14 years earlier (mean 12 years). The range of muscle nerve sympathetic activity was 9–59 in the first and 13–61 bursts/min in the second recording. Subjects maintained the level of muscle nerve sympathetic activity displayed previously, although with a slight but significant tendency to a higher outflow with increasing age.It is concluded that muscle nerve sympathetic activity is characterized by large inter-individual differences and strong intra-individual reproducibility over many years, with a tendency to increase with age. The age relationship is only in a minor part responsible for the variability, the cause of which remains unexplained. Because of the marked difference between individuals, strict normality criteria are difficult to define when comparing groups of subjects. There remains the risk of either obtaining spurious differences or obscuring a true abnormality. This is unlikely to apply when results in individual subjects are compared.     

High frequency discharges in sensory nerves following ischemia

The effects of ischemia and recovery from ischemia on afferent discharges recorded from dorsal root filaments were assessed in anesthesized cats. During ischemia produced by cross-clamping the lumbar aorta, some of the hindlimb afferents originating in muscle spindles exhibited a sustained high frequency discharge of 120--160 Hz, the so-called "explosion." During recovery from ischemia, nerve discharges appeared in previously inactive dorsal root afferent nerve fibers not of muscle spindle origin. The post-ischemic high frequency discharges appeared in bursts of action potentials at frequencies of 200--500 per second, with 6--32 spikes per burst; the bursts recurred at intervals of 120--600 msec. The nerve fibers exhibiting post-ischemic bursts could not be activated by muscle stretch, muscle tension, palpation, or tactile skin stimulation prior to or during the ischemia. No post-ischemic burst discharges could be detected in analogous experiments with the sural nerve. Intermediate size fibers from normal cutaneous and muscle mechanoreceptors were eliminated as possible origins of the post-ischemia activity. Possible sources include dorsal root ganglion cells or fibers whose sensory endings lie in deep structures such as the walls of the larger blood vessels.     

Segmental distribution of muscle weakness in SMA III: implications for deterioration in muscle strength with time

We examined 26 spinal muscular atrophy type III (SMA III) patients with SMNt deletions, searching for possible segmental distribution of muscle weakness. In those with disease duration of ≤11 years, the weakest muscles were upper lumbar innervated ones in the lower extremities. In the upper extremities, early involvement of triceps muscle suggested the possibility of lower cervical (C7) onset. Electrophysiologically, weaker muscles had a more severe reduction in the recruitment pattern, particularly in the lower extremities. However, severe reduction in recruitment was sometimes also observed in clinically strong muscles. In patients with disease duration of ≥16 years and regardless of disease duration, in those with disease onset at ≤3 years of age, weakness and severe electrophysiological changes were more widespread. These findings may suggest a progression in muscle weakness with time. When compared to 12 patients with Becker muscular dystrophy (BMD), early stage SMA III with weak iliopsoas-strong gluteus maximus stood in contrast to BMD with weak gluteus maximus-strong iliopsoas.     

Microneurographic analysis of muscle sympathetic nerve activity in amyotrophic lateral sclerosis

Muscle sympathetic nerve activity by (microneurograph) blood pressure and heart rate has been studied in patients with amyotrophic lateral sclerosis and in age-matched normal subjects (controls) at rest and during head-up tilt. Muscle sympathetic nerve activity in amyotrophic lateral sclerosis patients was significantly increased at rest unlike controls. There was no correlation between muscle sympathetic nerve activity and age in the patients with amyotrophic lateral sclerosis. Elevated muscle sympathetic nerve activity was present mainly in younger patients. There were no differences between blood pressure or heart rate in either group at rest or during head-up tilt in amyotrophic lateral sclerosis. The increase in muscle sympathetic nerve activity following tilt in the amyotrophic lateral sclerosis patients was less than in the controls, but they had no postural hypotension. The possible reasons for this observation of increased muscle sympathetic nerve activity at rest in amyotrophic lateral sclerosis are discussed.Corresponding Author     

The validity and reproducibility of the skin vasomotor test—studies in normal subjects,after spinal anaesthesia,and in diabetes mellitus

Skin sympathetic vasomotor control can be examined in the extremities by the skin vasomotor test. In this test the change in skin blood flow and skin temperature in the hand and foot in response to a cold stimulus is utilized as an index of distal sympathetic nerve fibre integrity. This is of importance in conditions such as diabetes mellitus as peripheral autonomic neuropathy is associated with orthostatic hypotension and diabetic foot complications. The validity and reproducibility of the test as a marker of distal sympathetic nerve function has been studied. The test was performed in nine healthy control subjects and in nine subjects (undergoing minor surgery) after a sympathetic nerve conduction block (L2–L3) was achieved in the lower extremities by spinal analgesia. Changes in skin temperature (p < 0.001) and skin blood flow (p < 0.005) in responses to cooling were significantly larger in the control group than in the group with spinal analgesia. Repeated skin temperature measurements on 42 occasions (test—retest period of 4 weeks) in eight healthy and 34 diabetic subjects indicated a reliability coefficient of 80%. We conclude, therefore, that the skin vasomotor test provides a valid and reproducible quantitative assessment of skin sympathetic nerve function in upper and lower extremities.     

Skeletal muscle pathology of mannosidosis in two siblings with spastic paraplegia

Summary Deficiency of -d-mannosidase was found in two siblings with muscle weakness and spastic paraplegia. A biopsy of the vastus lateralis muscle was studied by light and electron microscopy. Cryostat sections showed mild fiber size variation but no necrosis. Semithin Epon sections revealed many vacuoles in the muscle cells and fibroblasts. Electron microscopy showed that the vacuoles, presumably lysosomal, had a single limiting membrane and contained finely granular or granulo-reticular material, membranous structures, and electron-dense ovoids. The vacuoles were identical with those in lymphocytes and other cells of patients with mannosidosis. Disorganization of sarcomere alignment and widening of intermyofibrillar spaces were also observed. Deficiency of -d-mannosidase is considered to cause slowly progressing degeneration of muscle fibers.     

Muscle chemoreflexes and exercise in humans

This review focuses on the role afferent nerves from the contracting muscles play in linking muscle metabolism to the cardiovascular adjustments during exercise by means of a muscle chemoreflex. In the 1930s Alam and Smirk provided the first clear evidence that human (and animal) skeletal muscles are innervated by chemosensitive afferents that can evoke increases in arterial blood pressure. They proposed that the purpose of the increase in pressure was to improve blood flow to the active muscles. Subsequent studies have identified the slowly conducting group IV afferents as the major class of fibres participating in the sensory arm of this reflex. Most of these fibres travel via the dorsal roots to the ipsilateral spinal cord where they synapse in the substantia gelatinosa and release substance P or other peptide transmitters. The second order (or higher) neurons cross to the contralateral side of the spinal cord and travel rostrally to stimulate brainstem cardiovascular centres and increase arterial pressure. Current evidence favours the concept that substances associated with muscle acidosis provide the stimulus to the afferents. In humans, chemosensitive afferent activation causes a marked increase in vasoconstrictor efferent muscle sympathetic nerve activity. It is unclear if the muscle chemoreflex improves blood flow to underperfused active muscles by augmenting arterial pressure, or if the increase in sympathetic outflow restrains metabolic vasodilatation to regulate arterial blood pressure during activities like running or cycling.     

Intermittent stimulation of fusimotor fibres during slow stretch of muscle spindles in the cat

Responses of muscle spindles of the peroneus tertius muscle of the cat were recorded during intermittent fusimotor stimulation, applied during slow stretch, after muscle conditioning by stimulation of the nerve at the test length or at a length 2.5 mm longer. Some static and all dynamic axons evoked afferent bursts whose amplitude was relatively independent of the level of stretch response. Other static axons produced bursts that grew in size with the stretch.     

Recessive carnitine palmityl transferase deficiency: biochemical studies in tissue cultures and platelets

Summary In a new case of carnitine palmityl transferase (CPT) deficiency the defect was documented in muscle and muscle cultures with an isotope exchange reaction, using different concentrations of palmityl-dl-carnitine and a forward reaction with and without albumin. The defect was expressed in cultured skin fibroblasts only by the reverse and hydroxamate reactions. The parents and the patient's daughter had intermediate levels of the enzyme in platelets and fibroblasts, supporting the concept that CPT deficiency has an autosomal recessive pattern of inheritance. The growth pattern and development of muscle cultures in this CPT-deficient patient indicate that CPT activity may be sufficient to allow normal muscle differentiation in culture without lipid storage.     

Myoadenylate deaminase deficiency with progressive muscle weakness and atrophy caused by new missense mutations in AMPD1 gene: case report in a Japanese patient

A 46-year-old woman with exertional myalgia developed slowly progressive weakness in her lower extremities. She had slight muscle weakness in her facial and upper extremities, and severe muscle weakness and atrophy in lower extremities more marked in the proximal portions. Serum creatine kinase was slightly elevated. After ischemic forearm exercise test, blood ammonia had no elevation although lactate level increased normally. The computed tomography revealed that a characteristic distribution of skeletal muscle involvement with proximal and flexor muscles more severely affected than distal and extensor in the lower extremities. In addition, the left sternocleidomastoid muscle showed marked atrophy with an asymptomatic weakness of over 20 years duration suggesting abnormal development. Needle EMG examination showed a large number of easily recruited, short-duration, low-amplitude motor unit potentials in all extremities. Muscle biopsy showed absence of adenosine monophosphate deaminase activity with normal cytochrome c oxidase and phosphorylase activity. With the muscle enzyme activity assay, adenosine monophosphate deaminase activity was found to be lower than 0.2% of the controls. The DNA analysis revealed that she was compound heterozygote involving two missense mutations (R388W and R425H) in exon 9 and exon 10 of AMPD1 gene. This is the first report of primary myoadenylate deaminase deficiency with progressive weakness and atrophy caused by novel compound heterozygous mutations of AMPD1 gene, and suggests that adenosine monophosphate deaminase is closely related not only to energy metabolism but also to the development of skeletal muscle.