Tom Brismar

Subclinical nerve dysfunction in children and adolescents with IDDM

SummaryThe purpose of this study was to investigate whether young insulin-dependent diabetic patients still develop peripheral nerve dysfunction when using modern multiple insulin injection therapy and to elucidate if this correlated with various disease parameters. Seventy-five patients, 7 to 20 years old with a duration of diabetes of more than 3 years, and 128 age-matched healthy control subjects underwent bilateral studies of median, peroneal, and sural nerves. Presence of diabetes lowered motor conduction velocity (p<0.0001), sensory conduction velocity (p<0.0001) and sensory nerve action potential (p<0.05) in all examined nerves. The mean change in conduction velocity induced by diabetes was −4.8 m/s in the peroneal nerve, −3.3 m/s in the median motor nerve, −2.6 m/s in the sural nerve and −2.4 m/s in the median sensory nerve. Fifty-seven percent of the patients had abnormal conduction (values outside 95% predictive interval) which was seen most often in the motor nerves, especially in the peroneal nerve (41%) followed by the median nerve (24%). In multiple regression analysis, long-term poor metabolic control and increased body length correlated with nerve dysfunction identified in most examined parameters. Three patients had signs or symptoms suggestive of neuropathy. It is concluded that despite modern multiple insulin injection therapy, with reasonably good metabolic control, nerve dysfunction is still common in children and adolescents with insulin-dependent diabetes mellitus. Risk factors are increased height and long-term poor metabolic control.

EEG abnormalities with and without relation to severe hypoglycaemia in adolescents with type 1 diabetes

Aims/hypothesisThe aim of the present study was to identify whether adolescents with type 1 diabetes receiving modern multiple insulin injection therapy (MIT) have abnormal EEGs, and to elucidate possible correlations with a history of severe hypoglycaemia, poor metabolic control and nerve conduction defects.MethodsWe investigated 35 patients (age 14–19 years) with disease duration 7.6±4.6 years, and 45 healthy control subjects. EEG spectral components were obtained from 15-min recordings in resting, awake subjects. Nerve conduction was measured bilaterally in motor and sensory fibres in the median, peroneal and sural nerves.ResultsThe EEGs of patients showed an increase in slow activity (delta and theta) and a reduction in alpha peak frequency, both of which were most pronounced in the frontal regions (p<0.001). They also showed a decrease in fast activity, which was most pronounced bilaterally in the posterior temporal regions (alpha p<0.001, beta p<0.01, gamma p<0.001). A history of severe hypoglycaemia was correlated with a global increase in theta activity (p<0.01–0.05). Poor metabolic control, measured as acute and long-term HbA1c levels, was correlated with an increase in delta activity and a decrease in alpha peak frequency. The decrease in fast activity in the temporal regions was a separate type of abnormality because it had a different distribution, and was not correlated with the increase in delta/theta power, poor metabolic control or with hypoglycaemia.Conclusions/interpretationRecurrent severe hypoglycaemia and poor metabolic control are risk factors for EEG abnormalities in adolescents with type 1 diabetes receiving MIT treatment. In addition, we found pronounced abnormalities in the temporal regions that were not related to these risk factors.

Normal values of nerve conduction in children and adolescents

Healthy children and adolescents (n = 128) ranging in age from 6 to 20 years and in height from 114 to 193 cm underwent studies of median, peroneal and sural nerves bilaterally, including nerve conduction velocity, amplitude and motor distal latencies. Arms and legs were heated in all subjects to obtain skin temperatures around 34 degrees C. Both motor and sensory nerve conduction velocities were found to correlate more with height than with age. There was a strong negative correlation between height and peroneal conduction velocity (r = -0.40, P < 0.0001). On the contrary, a positive correlation was found between height and both median sensory (r = 0.30, P < 0.0001) and motor (r = 0.22, P < 0.001) conduction velocities. Skin temperature, even near 34 degrees C, had a strong effect on conduction velocity and motor distal latencies. It is concluded that consideration of height and temperature will improve the diagnostic safety of nerve conduction measurements in children and young adults.

The human EEG--physiological and clinical studies.

The present review summarizes the research in EEG performed by our group during the last 5 years. Our studies have been focussed on two areas: studies of variability and correlations in the oscillations during resting conditions of normal subjects, and the abnormalities related to type 1 diabetes. Recordings in normal subjects showed that also under standardized conditions with regular cycles of closed and open eyes, there is a temporal variability of the spectral components in EEG that necessitates samples>124 s in order to achieve estimates of alpha power with a coefficient of variation<0.1 in all recording channels (brain regions). The temporal variability in alpha and beta power demonstrates long-range temporal correlations, i.e., periods of large power (alpha or beta) are more likely to be followed by large power, and vice versa. The long-range temporal correlations were reproducible, especially during the closed-eyes condition, stronger in males than females, and not age dependent. In patients with type 1 diabetes, the alpha and beta power components were both decreased with similar nadirs in the posterior temporal regions, and the slow spectral components were increased in the frontal regions. The cognitive function was presently not studied but in a group of adolescents with diabetes we found a correlation between the presence of slow activity and the number of hypoglycaemic episodes. The loss of alpha and beta power was highly correlated which initiated a study of the normal alpha-beta correlation. A significant 1:2 phase synchronization was present between alpha and beta oscillations with a phase lag of about pi/2 in all electrode derivations. The strong frequency relationship between the resting beta and alpha oscillations suggested that they are generated by a common mechanism.

Experimental uremic neuropathy: Part 2. Sodium permeability decrease and inactivation in potential clamped nerve fibers

Potential recordings and potential clamp of isolated myelinated fibers from the sciatic nerve of acutely uremic rats showed a marked decrease in excitability related to a decrease in the specific Na permeability (P Na) of the nodal membrane. Mean value of the available P Na in the resting node of the uremic rats was 24% of the P Na in a control group. This change explained the decreased nerve conduction velocity in the acutely uremic rat. The Na current reversal potential was decreased in some fibers, reflecting an axoplasmic Na accumulation. The decrease in P Na was to a large extent caused by an increased inactivation, due to a negative shift (about 10 mV) of the steady state inactivation curve along the potential axis. The activation of P Na was similarly shifted (about 10 mV) to a more negative potential region. Such changes may be caused by elevated intracellular [Ca], suggesting a disturbance in Ca metabolism or an intracellular accumulation of cationic metabolites (which possibly have a similar effect) in rats with acute uremia.

Changes in electrical threshold in human peripheral neuropathy

A new method for analysis of excitability changes in human peripheral neuropathy is described. The range of the electrical threshold in a nerve is estimated in relative units from the ratio (S90-S10)/S10, where S10 and S90 are the stimulus voltages for 10% and 90% of maximal compound muscle potential. The ratio is increased if there is a fraction of high threshold fibres in the nerve; it is not affected by extraneural factors (e.g. distance to the nerve). The ratio was 0.16 +/- 0.03 in normals and significantly higher in subjects with chronic renal insufficiency or diabetes mellitus. Some of these had normal nerve conduction velocity. The ratio was markedly increased in the median nerve at the wrist in subjects with the carpal tunnel syndrome, which indicated that there are retrograde changes in the entrapped nerve fibres.

Experimental uremic neuropathy: Part 1. Decreased nerve conduction velocity in rats☆

Acute and chronic renal failure were induced in adult male albino rats by conventional surgical methods. The glomerular filtration rate of rats with chronic uremia was reduced to approximately 15% of normal. Despite this drastic degree of renal failure, the motor nerve conduction velocity (MCV) increased from 47.5 +/- 6.4 m/s, preoperatively, to 55.6 +/- 4.0 m/s after 4 weeks. In rats with acute uremia, MCV decreased from 51.4 +/- 3.0 m/s to 45.2 +/- 2.7 m/s after 48 h. The conduction velocity, measured in vitro of excised sciatic nerves was 55.2 +/- 4.4 m/s in acute uremia and 64.7 +/- 4.7 m/s in a control group. There was no difference in the refractory period between these groups. It is concluded that this decrease in the nerve conduction velocity was not caused by changes in the composition of the extracellular fluid but rather by changes in the nodal membrane function.

Impaired recovery in diabetic rat nerve following anoxic conduction block

It is well documented that diabetic rats and subjects have a paradoxical resistance to ischemic conduction block although the nerves of diabetes are more susceptible to entrapment neuropathies. The aim of the present study was to further analyze the effect of anoxia on the diabetic nerve. Nerve conduction was measured in vitro in desheathed sciatic nerves from spontaneously diabetic rats (BB-Wistar) and age-matched controls. After onset of anoxia the compound action potential (CAP) decreased to 50% in 17 min in diabetic rat nerves and 8 min in normals. Following reoxygenation CAP recovered to 50% in 30 s in normal rat nerves and after 3 min the recovery was 92%. In nerves from diabetic animals 50% recovery took 4 min, but still after 12 min CAP was suppressed to a 60% level of the original. Longer periods of anoxia did not impair the recovery in normal nerve as it did in the diabetic ones. This defective recovery after anoxia in nerves from diabetic animals may be relevant for the understanding of the pathogenesis of entrapment neuropathies in diabetic subjects.

No acute effect of high blood glucose on nerve conduction in adolescents with IDDM

The aim of the present study was to evaluate the acute effect of high blood glucose on the motor and sensory nerve conduction in adolescents with IDDM. Four patients, 15-18 years old, with a history of diabetes from 5 to 9 years underwent repeated studies of the conduction properties in the median, peroneal, and sural nerves within a 10-day period. Capillary blood glucose was drawn immediately before and after each examination. Repeated measurements in each patient revealed only a small variation in the values of ten nerve conduction parameters despite of large differences in the blood glucose level. A multiple regression analysis of the data from all patients in a total of 20 measurements gave P-values between 0.18 and 0.96, i.e. there was no correlation between any of the ten studied conduction parameters and the prevailing blood glucose level. This supports the view that nerve dysfunction is a consequence of long-term poor metabolic control (HbA1c) and not dependent on the acute effect of hyperglycemia in adolescents with IDDM.

Excitability changes reveal decreased sodium permeability in neuropathy

Nerve excitability was tested in isolated sciatic nerves of rats with acute uremia. Larger than normal stimulating pulses were required to elicit a maximal compound potential, whereas the relative refractory period was unaffected. The threshold range, relative to the absolute threshold, was a good measure of the decreased excitability and may be a useful clinical method.