Autonomic dysfunction in non-diabetic terminal uraemia

R-R variations in the ECG were studied as a sign of autonomic dysfunction in 44 non-diabetic patients with terminal uraemia treated with intermittent haemodialysis. A severe impairment of this parasympathetic vagal reflex was found though there were only mild signs of diffuse polyneuropathy. No acute effect was associated with haemodialysis. There was no correlation between either the R-R variations and the polyneuropathy-index or the total dialysis time. Patients with chronic glomerulonephritis, pyelonephritis and polycystic kidney disease were equally affected.     

Central conduction and autonomic nervous function in HMSN I.

CNS conduction and autonomic nervous function were investigated in 15 patients with HMSN I. Central motor conduction time (CMCT) was estimated with magnetic brain stimulation and electrical nerve root stimulation. Somatosensory evoked potential (SEP) and visual evoked potential (VEP) were used for assessment of central sensory and visual conduction. Autonomic effector organ functions were assessed with the R-R variation test for parasympathetic function, and the sympathetic skin response test (SSR) for skin sympathetic sudomotor activity. Five of the patients had prolonged CMCT. Central sensory conduction was normal in 3, and slightly prolonged in 1 of the patients, but could not be estimated in 11 due to lack of response from the cervical recording. VEP was abnormal in 2 patients. R-R variations during normal breathing were low in 8 of 15 patients, and low also during deep breathing in 1 of 15. The SSR test was pathological in 5 of 15 patients. Thus, impaired central conduction and/or autonomic dysfunction was not an uncommon finding in patients with HMSN I.     

R-R variations, a test of autonomic dysfunction

ABSTRACT- Beat-to-beat variation of the heart rate was studied as a test of autonomic function. Recordings were made during quiet breathing, deep breathing and tilting from supine to upright position. The heart rate variations were expressed as a % of mean R-R interval. In order to establish normal criteria, the influence of age, wakefulness and intra-individual variations was studied in healthy volunteers. A negative correlation with age was found for all measured parameters. Patients with diabetic polyneuropathy differed from age-matched controls. Patients with symptoms of autonomic failure showed smaller variations than those without such symptoms.     

Ultrasonography of the peripheral nervous system in the early stage of Guillain‐Barré syndrome

Ultrasonography can be used to visualize peripheral nerve abnormalities in immune‐mediated neuropathies. The objective of this study was to prove the role of ultrasonography (US) in acute phase of Guillain‐Barré syndrome (GBS). Systematic ultrasonic measurements of several peripheral nerves including the vagal nerve as well as the sixth cervical nerve root were performed in 18 patients with GBS at days 1–3 after symptom onset and compared to 21 healthy controls. Nerve conduction studies (NCS) of corresponding nerves were undertaken. Consequently, significant differences between the groups were found in compound muscle action potential amplitudes, F‐wave latency, and persistency. Ultrasonic cross‐sectional areas (CSAs) showed significant enlargement in all nerves except of the ulnar nerve (upper arm) and the sural nerve compared to healthy controls, most prominent in proximal and middle median nerve (p < 0.01). The vagal nerve also showed enlargement compared to controls (p < 0.05), which was most pronounced in patients with autonomic dysfunction compared to patients without (p < 0.05). C6 root diameter showed a significant correlation to the amount of cerebrospinal fluid (CSF)‐protein (Pearson correlation, p < 0.05). US shows nerve enlargement in several peripheral nerves including vagal nerve and C6 root in acute phase of GBS and could be an additional diagnostic tool for example, in GBS of atypical onset and autonomic dysfunction.     

Experimental studies of the effects of extrinsic factors on conduction in normal and demyelinated nerve. 1. Temperature.

Previous studies in experimentally demyelinated mammalian nerves have demonstrated that a reversible conduction block occurs with small increases of temperature within the animal's normal body temperature range. This phenomenon is believed to be the mechanism for clinical temperature effects in multiple sclerosis. This study examines some quantitative thermal relationships in demyelinated nerves of guinea pigs with experimental allergic neuritis. The observed results in normal and experimental animals are in good agreement with previous theoretical calculations based on the effects of temperature on the voltage and time-dependent behavior of the ionic permeabilities of the nodes of Ranvier. Guinea pigs with increasing motor dysfunction generally exhibited corresponding increases in the overall latency of the conducted action potential, as well as decreases in amplitude. In addition, the lower the initial velocity increment per degree of temperature elevation, the lower was the temperature at which conduction block began to occur. Except for a few cases in which the recorded action potential was bimodal, with response at both normal and prolonged latency, the results tended to indicate a remarkedly uniform involvement of the sciatic nerve within the region of temperature control.     

T-lymphocyte subsets, functional deficits, and morphology in sciatic nerves during experimental allergic neuritis

Conduction velocities, demyelination, "macrophage/dendritic" cells, different sets of T-lymphocytes, and immunoglobulins were estimated in sciatic nerves during various phases of experimental allergic neuritis in Lewis rats. Demyelination was minimal day 15 postimmunization (p.i.) when conduction velocity already was reduced, somewhat more pronounced day 17 p.i. when nerve conduction was blocked, and most pronounced day 23 p.i. when nerve conduction partially had recovered. This suggests a dissociation between the degree of demyelination and the functional deficits. Decrease of sciatic nerve conduction velocities coincided with endoneurial appearance of T-lymphocytes and "macrophage/dendritic" cells, as well as endoneurial immunoglobulins, day 15 p.i. Later partial functional recovery occurred in parallel with the disappearance of T-cells. The degree of functional deficits thus correlated with the number of endoneurial T-lymphocytes. T-cells may, directly or indirectly, initiate several of the disease components in experimental allergic neuritis, including the nerve conduction deficit.     

Conduction failure and nerve conduction slowing in experimental allergic neuritis induced by P2-specific T-cell lines

P2-specific T cells (LiP2/A) mediate experimental allergic neuritis (EAN) in the Lewis rat after adoptive transfer to naive recipients. After a latent period of 4 days, injection of 2 X 10(6) line cells induced fulminant paraplegia and complete conduction failure in the peripheral nerves and roots, resembling acute axonal breakdown. Injection with 10(6) cells caused milder clinical signs, nerve conduction failure, and conduction slowing. Clinical and electrophysiological recovery from adoptively transferred EAN was nearly complete and its time course was inversely correlated to the initial severity of EAN. These findings suggest that EAN induced by the P2-specific T-cell line can lead to a profound and rapidly evolving nerve dysfunction in a dose-dependent fashion.     

Electrocardiographic changes during postnatal development in conscious swine with cardiac autonomic imbalance

Using a conscious swine model, we studied the effects of different patterns of cardiac autonomic denervation on alterations of R-R and Q T intervals for 8 postnatal weeks. Newborn pigs were assigned randomly to four different groups: sham-operated controls (C), stellate ganglion ablation (SGX), either left (LSGX) or right (RSGX), and the right cardiac vagus nerve (RCVX) transection. The ECGs were recorded by telemetry while animals rested quietly or were judged behaviorally to be asleep. Analyses of the ECG included measurements of R-R and Q-T intervals, as well as corrected Q-T intervals (QTc). Poincaré plots were used to display age-related differences in R-R and Q-T intervals. For stellectomized animals, significantly prolonged R-R intervals were first observed at post-surgical week 3 in the RSGX group and at week 5 in the LSGX group. Significantly prolonged QTc was found only in the RSGX group. In the RCVX group, shortened QTc and R-R intervals were noted at 6 and 7 weeks after denervation. Furthermore, three of six RSGX animals (50%) and one of four RCVX animals (25%) exhibited marked pauses in sinus rhythm that were unrelated to changes in heart rate or to sinus arrhythmia. These results in conscious animals support our hypothesis that abnormal autonomic innervation of the heart during maturation, e.g., withdrawal of vagal cardiac modulation or asymmetry of sympathetic innervation, impairs cardiac electrical stability.     

Autonomic dysfunction in Machado-Joseph disease

OBJECTIVE: Machado-Joseph disease is an autosomal dominant spinocerebellar ataxia with expanded trinucleotide repeats. Although autonomic nervous system degeneration was documented in postmortem reports, the autonomic dysfunction in patients with Machado-Joseph disease, either in clinical analysis or electrophysiological investigations, has not yet been studied in detail. METHODS: Fifteen patients with genetically confirmed Machado-Joseph disease and 34 healthy subjects were studied. The study design included a detailed questionnaire, R-R interval variation on deep breathing or Valsalva maneuver, and sympathetic skin response evoked by electrical stimulation of the median nerve or magnetic stimulation of the neck. RESULTS: Sixty-seven percent of patients had at least 3 symptoms involving different aspects of autonomic functions. Voiding problems and thermoregulatory disturbance were the most common symptoms. Ten (71%) of 14 patients had abnormal R-R interval variation with a significant reduction of the mean ratio. Prolonged latency or absence of sympathetic skin response to electrical stimulation was identified in 73% of patients and to magnetic stimulation, in 53%. R-R interval variation and sympathetic skin response showed good correlation with the functional stage. Electrical stimulation revealed the highest sensitivity, specificity, and positive predictive value compared with other tests. CONCLUSION: The present investigation documents that autonomic dysfunction is not uncommon in patients with Machado-Joseph disease and might be related to the clinical progression.     

R-R variations in Guillain-Barré syndrome: a test of autonomic dysfunction

ABSTRACT- As we have earlier shown, variations in the R-R interval of the ECG can be used as a measure of autonomic function. This test was applied to 6 patients with Guillain-Barré syndrome at different times during the course of the disease. Severe but temporary impairment of autonomic function was found, which was maximal at 2–6 weeks after the onset of clinical symptoms and gradually improved to normal levels over a period of 3–18 months. This paralleled clinical recovery. The results suggest that this test of R-R variations is a reliable method for establishing and following an autonomic dysfunction in patients with Guillain-Barré syndrome.     

Comparative analysis of autonomic and somatic dysfunction in chronic uraemia

The relationship between autonomic dysfunction and peripheral somatic neuropathy was investigated in uraemics. The battery of autonomic tests included R-R interval variation test, deep breathing, Valsalva manoeuvre, heart rate and blood pressure responses to standing, and sustained handgrip. Maximum conduction velocity along sensory and motor fibres of the posterior tibial nerve was measured. An impairment of parasympathetic reflexes was more frequent than a sympathetic damage, but with no relationship to the degree of electrophysiological disturbances. Cardiovascular autonomic dysfunction and somatic neuropathy in uraemia result to be two different entities in incidence and perhaps in pathogenesis.     

Impairment of repetitive impulse conduction in experimentally demyelinated and pressure-injured nerves

Repetitive impulse conduction was studied in segmentally demyelinated peripheral nerves in guinea-pigs with experimental allergic neuritis (EAN) and in pressure-injured frog sciatic nerves. Normal guinea-pig sciatic-peroneal nerves maintained at 37°C conducted compound action potentials with only minor amplitude decreases at stimulus frequencies up to 200/sec. In contrast, nerves in EAN guinea-pigs maintained at 37°C demonstrated a rapidly progressive decrease in action potential amplitude when stimulated as slowly as 10-25/sec. The decrease is greater the higher the frequency of stimulation. At 100 stimuli/sec all EAN preparations showed more than a 50% reduction in action potential amplitude. These effects are reversible. In pressure-injured frog sciatic nerves similar effects occurred at stimulus frequencies as low as 50/sec. Normal frog nerves conducted up to 200 impulses/sec with little amplitude decrease. The probable mechanism and clinical significance of these results are discussed.     

Autonomic nerves in experimental allergic neuritis in the rat

Summary After experimental allergic neuritis (EAN) was induced in 16 male Lewis rats with bovine peripheral myelin and adjuvants, peripheral nerves were examined morphologically at intervals of 12–21 days post inoculation (dpi). Signs of motor involvement were present in ten rats and were first elicited 12 dpi. They ranged from tail droop to complete lower limb paralysis. Autonomic nervous system (ANS) involvement was studied by contrasting morphological findings in the cervical sympathetic nerves (CSN), which are poorly myelinated and vagal nerves (VN) which contain numerous myelinated fibers in the endoneurium. Edema, perivenular infiltrates, and demyelination appeared in the VN of seven of nine neurologically affected rats, while the CSN showed edema and infiltrates in only one rat. ELISA assays were negative for anti-galactocerebroside antibody, and electron microscopy failed to show abnormalities of Schwann cells.Supported by NS-14162 from the NINCDS, from the Kroc Foundation, by the Medical Research Council UK, and by the Veterans Administration Research ServicePresented in part at the 60th Annual Meeting of the American Association of Neuropathologists in San Diego, California, June 15, 1984     

In vivo treatment of rats with monoclonal antibodies against gamma interferon: effects on experimental allergic neuritis

To elucidate the role of gamma interferon in experimental allergic neuritis (EAN) a mouse monoclonal antibody (DB-1) directed against rat gamma interferon was used to treat rats during different phases of the development of experimental allergic neuritis (EAN). The effects of this treatment were followed by clinical evaluation, and in some instances by immunohistochemical analysis of lymphoid organs and affected nerves for presence of MHC class II antigens and various T cell subsets. DB-1 treatment given after onset of clinical symptoms (Day 15 after immuniozation with myelin) shortened disease duration, compared with non-treated EAN controls. Affected nerves of DB-1 treated animals showed reduced expression of MHC class II antigens and lower numbers of T lymphocytes within the affected nerves. In contrast, when DB-1 treatment was given on the day of immunization (Day 0), the disease duration increased, and when given before onset of the disease (Day 9) the clinical course was not significantly affected. The results support an important role for gamma interferon in the pathogenesis of EAN.     

Neuropathy in tetanus

Thirty-four cases of severe tetanus were studied. On clinical examination weakness and sensory loss compatible with peripheral neuropathy was found in 27. The pattern was usually asymmetrical, the commonest nerves affected being ulnar, median and lateral popliteal, although occasionally circumflex, musculocutaneous, femoral and facial nerves were also involved. Electrophysiological studies showed spontaneous activity resembling denervation potentials, diphasic and positive sharp waves. In some muscles there was also activity resembling spontaneous firing of motor units. Motor and sensory conduction velocities in the affected nerves were moderately reduced and the amplitude of sensory potentials was also reduced. No conduction was found in 11 nerves in 8 patients on initial studies, but 4 out of 7 nerves that could be studied showed rapid recovery. Although most of the nerves in the rest of the patients showed clinical recovery, conduction velocities showed improvement most often when examined about 10 weeks after the onset of trismus. The clinical and electrophysiological evidence suggests the involvement of peripheral nerves in severe tetanus. Serum neuritis, hypersensitivity reaction to tetanus toxoid or drug-induced neuropathy have been ruled out.     

Peripheral nervous system demyelination from systemic transfer of experimental allergic neuritis serum

The ability of systemically transferred experimental allergic neuritis (EAN) serum to produce EAN lesions in recipient animals was studied. Seventeen Lewis rats received five daily 1-ml intraperitoneal (i.p.) injections of sera from rabbits with EAN induced with bovine myelin/complete Freund's adjuvant (CFA). Another 17 rats received similar injections of sera from rabbits inoculated with CFA alone. On day 0 (the first day of i.p. injections), all rats were injected in the proximal tibial branch of the right sciatic nerve with a single 10-microliters injection of 0.03 M 5-hydroxytryptamine (5-HT) in sterile 0.15 M saline. Proximal tibial branches of left sciatic nerves received similar single injections of saline alone. Animals were then studied using electrophysiological and histological techniques. In all animals, intraneural saline injection had no significant effect upon nerve conduction. In the presence of circulating CFA serum, 5-HT injection caused a mild gradual decrease in amplitude ratio becoming maximal by day 17 (P < 0.005) and partially resolving by day 28. In contrast, in the presence of circulating EAN serum, 5-HT injection caused a more rapid and severe decrease in amplitude ratio becoming maximal by days 6-10 (P < 0.001 day 6; P < 0.0001 day 10) and completely resolving by day 28. Histological analysis of nerves injected with 5-HT in CFA serum-treated animals showed areas of mild demyelination, axonal degeneration and some fibre loss consistent with needle trauma. In contrast, 5-HT-injected nerves in animals administered EAN serum showed areas of marked cellular infiltration and severe demyelination in association with numerous debris-filled infiltrating cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patterns of conduction impairment in experimental allergic neuritis. An electrophysiological and histological study.

Electrophysiological and histological studies of peripheral nerve were performed in 24 Lewis rats with experimental allergic neuritis (EAN) in which disease had been induced by a single myelin and adjuvant inoculation in one footpad. Demyelination was demonstrated in transverse nerve sections from ventral roots, proximal sciatic nerves and also in distal plantar nerves. Histological and electrophysiological assessments showed that injected limbs were more affected than uninjected limbs. Neurophysiological studies demonstrated two distinct patterns of conduction failure based upon proximal/distal compound muscle action potential (CMAP) amplitude ratios in both uninjected and injected limbs. Slightly more than half of all nerve trunks showed a mildly reduced distal CMAP amplitude irrespective of stimulus origin. The rest displayed a more severe reduction of distal amplitude that was length-dependent, becoming smaller with proximal stimulation. Histological lesions in plantar nerves were often more severe than those in proximal sciatic nerves or ventral roots. Axonal degeneration was an uncommon finding. This study has demonstrated patterns of peripheral nerve conduction impairment similar to those reported in patients with inflammatory demyelinating neuropathy. Moreover, it has shown that a low distal CMAP amplitude may result from demyelination of distal motor nerve segments and not necessarily from axonal degeneration.     

QTc interval, and autonomic and somatic nerve function in diabetic neuropathy

QTc intervals were measured using an electrocardiogram and other autonomic function tests, in 66 neuropathy patients with non-insulin-dependent diabetes mellitus (59.0±12.5 years; mean ± SD). The change in R-R interval did not influence the QTc interval, as calculated by the equation: QTc =QT+(1000-R-R)/7 (ms), compared with the conventional Bazett's equation which appeared to overcompensate in the case of a small R-R interval. The QTc interval in the diabetic patients was significantly longer than that in age-matched controls. The QTc interval showed an inverse correlation with the coefficient of variation of the R-R interval and skin blood flow at rest. However, no correlation was found between QTc interval and blood pressure change, change in heart rate on standing, or results of the sympathetic skin response. The QTc interval did not correlate significantly with motor or sensory nerve conduction parameters. We conclude that the QTc interval can be a simple and useful autonomic indicator for diabetic neuropathy relatively independent of other abnormalities of autonomic and somatic nervous system function. Clin Auton Res 8:139–143     

Autonomic dysfunction in vasculitic neuropathy--special reference to sudomotor function

We examined autonomic functions in 14 patients with peripheral neuropathy caused by necrotizing vasculitis. These patients consisted of three allergic granulomatous angitis (Churg-Strauss syndrome, AGA), two systemic lupus erythematosus (SLE), two progressive systemic sclerosis (PSS), one mixed connective tissue disease (MCTD), one polyarteritis nodosa (PN) and five nonsystemic vasculitis. All of them were proven to have a vasculitis by sural nerve, muscle or skin biopsy. Sixteen age- and sex-matched healthy volunteers were also examined. Local sweating induced by intradermal injection of pilocarpine and nicotine (a concentration of 10(-4) g/dl, 0.1 ml) was measured with ventilated capsular method on the forearm and lower lateral leg at 23 degrees C of room temperature and 40% of relative humidity. Other autonomic functions including skin temperature at rest and after cold loading (15 degrees C, 6 minutes), variation in the R-R interval of heart beat (CV%), orthostatic hypotension and bladder dysfunction were also monitored. A decrease in sweat rate and recovery rate of skin temperature after cold-loading was seen more frequently in patients with necrotizing vasculitis than normal volunteers. Abnormality in the local sweat response against nicotine and pilocarpine was more frequently present in the involved area of somato-sensory and motor nerves as compared with those in the non-involved area. An occurrence of decrease in recovery rate of skin temperature after cold-loading also well correlated to the region of somato-sensory- and motor involvement. So far other autonomic dysfunction, only one patient had orthostatic hypotension, impotence and bladder dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation in patients with progressive spinal muscular atrophy

To elucidate autonomic function in spinal muscular atrophy, we evaluated finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation in 10 patients with spinal muscular atrophy: 7 of type 1, 2 of type 2, and 1 of type 3. Results of finger cold-induced vasodilatation, sympathetic skin response, and R-R interval variation were compared with those of healthy children. Finger cold-induced vasodilatation was abnormal in 6 of 10 patients with spinal muscular atrophy; it was normal in the healthy children. The mean sympathetic skin response latency and amplitude did not differ significantly from those of the healthy children. Amplitudes of sympathetic skin response to sound stimulation were absent or low in all six patients with spinal muscular atrophy. No significant difference was found in the mean R-R interval variation of patients with spinal muscular atrophy and healthy children. Results show that some patients with spinal muscular atrophy have autonomic dysfunction, especially sympathetic nerve hyperactivity, that resembles dysfunction observed in amyotrophic lateral sclerosis.