Comparison of vibration perception thresholds obtained with the Neurothesiometer and the CASE IV and relationship to nerve conduction studies.

AIMS: Vibration perception thresholds (VPTs) are used frequently to assess somatosensory pathways in clinical trials. Different equipment, testing paradigms, and stimulation sites produce varying results which make comparisons between trials and patient populations challenging. Information comparing the VPT obtained with the Neurothesiometer with that with the Vibratron is available, but not for a similar comparison with the CASE IV (computer-assisted sensory examination device). METHODS: Subjects (n = 478) including reference, non-neuropathic subjects with diabetes mellitus (DM), and diabetic patients with mild, moderate and severe diabetic sensorimotor polyneuropathy (DSP) had VPTs measured with the CASE IV and Neurothesiometer, as well as standard sural nerve conduction studies (NCS), all performed during the same half-day. The dorsum of the foot was used as the site of stimulation for the CASE IV VPT determination and the distal phalanx of the first toe for the Neurothesiometer. RESULTS: VPTs by the CASE IV and the Neurothesiometer compared moderately by linear regression analyses (R2 = 0.547, P < 0.0001), and by 95% confidence intervals. Sensitivity for the diagnosis of mild DSP was 70% with the Neurothesiometer and 49% with the CASE IV. VPTs determined by either the Neurothesiometer or the CASE IV correlated with similar agreement to the sural nerve action potential amplitude as determined by nerve conduction studies (NCS) (R2 = 0.456 and 0.461, respectively, P < 0.0001). CONCLUSIONS: The results demonstrated a significant correlation of VPT values in different stages of DSP obtained by the two methods. The Neurothesiometer was more sensitive for the diagnosis of DSP, particularly in those with mild neuropathy. Similar correlations between VPTs and electrophysiological parameters were observed, indicating that both methods are valid, and thus the Neurothesiometer may be preferable due to the ease and rapidity of testing by this method.     

The Value of the Neurometer in Assessing Diabetic Neuropathy by Measurement of the Current Perception Threshold

The Neurometer is a relatively new device for assessing neuropathy by measuring current perception threshold (CPT). The study aim was to assess the ability of the Neurometer to distinguish between different types of nerve fibre damage by using different frequencies (2000 Hz, 250 Hz, and 5 Hz) of electric stimulus (high frequencies for large fibres and low frequencies for small fibres) and comparing the results with standard sensory tests of vibration perception threshold (VPT) and thermal perception threshold (TPT). CPT was determined on index finger and great toe of 51 patients with diabetic neuropathy and 28 non-diabetic control subjects, age and sex matched. CPT in neuropathic patients could be distinguished from controls at all three frequencies in both feet and hands (p < 0.05). The best correlation was found between CPT at 2000 Hz and VPT (r = 0.48, p < 0.001) in the feet suggesting a degree of neuroselectivity. Internal correlations between CPT at the three frequencies showed the weakest correlation between CPT at 2000 Hz and 5 Hz (r = 0.27, p < 0.005), suggesting also that possibly different types of fibres were examined. CPT reproducibility was better in control (CV = 6.4–27.7%), than in neuropathic subjects (CV = 28.4–52.3%), although the coefficient of variation was comparable to that of standard tests of sensory function, VPT and TPT. The Neurometer is a simple instrument to use in clinical practice. It has a degree of neuroselectivity but like all subjective sensory tests has a large variability.     

Maintenance of gaseous homeostasis in chronic coronary insufficiency

Mechanical resistance of erythrocytes was studied in patients with chronic coronary insufficiency and normal subjects using an original method (the blood sample was subjected to vibration effects after which the percentage of destroyed cells was determined). Erythrocyte resistance was assessed at 40 dB vibration and the frequencies of 125, 250 and 500 Hz. A vibration of 40 dB at 250 Hz destroyed 33.0 +/- 0.9% of erythrocytes in normal subjects, and 17.0 +/- 1.2% in the patients (p less than 0.001), an evidence of considerable rejuvenation of the erythrocyte population that helps to maintain normal myocardial oxygen consumption even in conditions of a 12% reduction of coronary flow owing to a smaller shunted oxygen inflow.     

Subcortical somatosensory evoked potentials in patients with hepatic encephalopathy caused by severe acute hepatitis

We studied the median nerve stimulated somatosensory evoked potentials (SEP) of 23 patients with hepatic encephalopathy (HE) resulting from severe acute hepatitis and 22 healthy volunteers. Ten patients who improved and survived more than 60 days were classified as Group 1 and the remaining 13 patients who died shortly after the SEP studies were classified as Group 2. The mean N9-N13 interpeak latencies (IPL) were not different among control and two patient groups. The mean N13-N20 IPL of Group 2 was significantly prolonged when compared with normal controls (P < 0.001) and Group 1 (P < 0.001). Five of the six patients with abnormal N13-N20 IPL died of hepatic failure within 24 h after SEP testing. The occurrence of abnormal subcortical conduction together with cortical dysfunction suggested that brain damage in terminal hepatic encephalopathy was diffuse. The presentation of abnormal prolongation of N13–N20 IPL of SEP during the course of severe acute hepatitis indicated a poor prognosis. Peripheral somatosensory conduction is unaffected even in terminal HE.     

Somatosensory evoked potentials in hepatic encephalopathy

Median nerve somatosensory evoked potentials were recorded from 33 patients with various degrees of hepatic failure and from 10 age-matched controls. Within 20 ms poststimulation, one negative peak (N13) could be recorded from the middle of the back of the patient's neck at the C2 vertebral level. Within 150 ms, three negative and three positive peaks, sequentially designated as N1, P1, N2, P2, N3, and P3, could be recorded from the scalp over the contralateral sensory cortex. There was a progressive prolongation of peaks and interpeak latencies correlating with the severity of hepatic encephalopathy. In 10 patients with hepatic failure but no clinical evidence of hepatic encephalopathy, latencies of peak N3 and P3 were delayed and N1-N3 interpeak latencies were prolonged. Thirteen patients with grade 1 or 2 hepatic encephalopathy showed further delayed latencies of peaks P2, N3, and P3, further prolonged N1-N3, N1-P2 interpeak latencies, and distortion of waveforms. Peaks N2, P2, N3, and P3 were further delayed, and even disappeared in 10 patients with grade 3 or 4 hepatic encephalopathy. However, central conduction time (N13-N1 interpeak latency) was not prolonged in all stages of hepatic failure. In addition, serial somatosensory evoked potential studies correlated well with the clinical course. The present data suggest that somatosensory evoked potential recording is a reliable objective method in the early assessment and monitoring of hepatic encephalopathy.     

Changes in central and peripheral nervous system function during hypoglycemia in man: an electro-physiological quantification.

We measured somatosensory evoked potentials (SEP) in normal subjects during acute (group A) and moderately prolonged (group B) hypoglycemia. We considered the following parameters: peripheral conduction velocity (wrist-Erb CV), conduction time (CT) between brachial plexus and the cervical cord (Erb-N13) and central CT from the cervical cord/lower brainstem lemniscal pathway to the cortex (N13-N20). In group A, the electrophysiological parameters did not change significantly throughout the study. In group B, mean N13-N20 CT increased from a basal values of 5.82 +/- 0.11 to 6.22 +/- 0.11 msec at 105 min (p less than 0.02) and 6.33 +/- 0.11 msec at 120 min (p less than 0.05). This study indicates that neither acute nor moderately prolonged hypoglycemia influence the peripheral nerve function in normal subjects and provides evidence that hypoglycemia as low as 2.4 mmol/L, lasting more than 60 min, can significantly increase the conduction time of central somatosensory pathways.     

EMG and evoked potentials in adrenomyeloneuropathy

In a 31 year old patient with adrenocortical gland insufficiency and minor clinical signs of involvement of peripheral and central nervous system an adrenoleucodystrophy was diagnosed, based upon the characteristic elevation of hexacosanoic acid in plasma. The motor and sensory nerve conduction velocities in upper and lower extremities were markedly reduced; in accordance, the somatosensory evoked potentials showed distinct reduction in the peripheral part. In contrast, the interpeak latencies N 20 - NSEP 3 (median nerve) and N 22 - P 40 (tibial nerve) were in the upper normal range, so that a damage of the central sensory system could not be evaluated. The visual and brainstem acoustic evoked potentials were a little prolonged. The problems in differential diagnosis of this form of adrenoleucodystrophy, which especially involves the peripheral nervous system, are discussed.     

Diabetic neuropathy as a heterogeneous syndrome: multivariate analysis of clinical and neurological findings

We quantitatively assessed peripheral and autonomic nerve function in diabetic patients and compared them with various parameters of their diabetic status. Motor and sensory nerve conduction velocity (MCV, SCV), vibratory perception threshold (VPT) and the coefficient of variation of the ECG R-R interval (CV R-R) were measured in 85 diabetic patients aged 20-59 years. These values were compared with those of age-matched healthy subjects. Moreover, in 53 patients, MCV, SCV, VPT and CV R-R were investigated by multivariate analysis in relation to clinical parameters. In diabetics, MCV, SCV and CV R-R were significantly lower and VPT was higher than in age-matched healthy controls. The prevalence of impaired values in diabetics was 70% for VPT in the toe, 60% for SCV, and 55% for MCV, CV R-R and VPT in the finger. Impairments of MCV, SCV, CV R-R and VPT were closely correlated with diabetic retinopathy, proteinuria and duration of disease. Categorical regression analysis (multivariate analysis) revealed that the impairment of conduction velocity was closely related to diabetic retinopathy and to hypo- or areflexia, that the impairment of the vibratory perception threshold was related to ischemic changes in ECG and to hypo- or areflexia, and that the reduction of CV R-R was related to orthostatic hypotension and to proteinuria. These findings suggest that diabetic neuropathy progresses in parallel with other complications, and that it is a heterogeneous syndrome rather than a single entity.     

Central nervous system involvement in elderly patients with non-insulin-dependent diabetes mellitus

Summary We examined cognitive functions and central conduction velocities in 20 patients, over 63-year old, with NIDDM compared with 20 normal, age-matched controls. Mean conduction velocity of median nerve, was significantly lower in diabetics than in controls, but absolute values were within normal range. Neurological examination showed clinical signs of lower limbs neuroperipheral involvement. Only one cognitive subtest performance was abnormal whereas there was no impairment in central conduction velocities. In our study population, although median nerve conduction velocity values may introduce a bias of low peripheral neuropathy incidence, there was no evidence of a massive or progressive specific central nervous system involvement caused by NIDDM.     

Does instantaneous blood glucose affect vibration perception threshold measurement using biothesiometer?

Diabetic neuropathy is a common and troublesome complication of diabetes mellitus. Vibration sensation is a measure of large fiber nerve conduction, which is very commonly affected in diabetes. The present study addresses the question of whether vibration perception threshold (VPT) measurement using a biothesiometer is reproducible under different levels of blood glucose at different hours of the day. Seventy-five diabetic patients, 31 insulin-dependent diabetes mellitus and 44 non-insulin-dependent diabetes mellitus, with mean age 50.33+/-14.22 years (21-70 years) and diabetes duration of 14.3+/-10.6 years (1-60 years) were included in the study. Forty-one patients were male and 34 were female. In conclusion, VPT was found to be reproducible under different blood glucose levels at different hours of the day, which is affected only by the height of the patient.     

Regional variation and changes with ageing in vibrotactile sensitivity in the human footsole

Recently there has been indirect evidence suggesting that age-related elevation in footsole vibration detection may be associated with balance and gait dysfunction. As a first step in investigating this dysfunction, the current study determined by how much plantar vibration sensation decreases as a function of age, and if change is dependent on frequency and location of vibration application. Vibration thresholds were assessed at 4 frequencies (25-400 Hz), at 55 locations, and in young and older participants. Results showed there were 3 regions of sensitivity on the footsole: the ball/medial arch, the lateral border of the foot and heel, and the toes. Thresholds for fast-adapting type I receptor (FAI)-mediated frequencies were age invariant; however, thresholds for fast-adapting type II receptor (FAII)-mediated frequencies increased with age. These changes may be one of many factors contributing to age-related changes in gait.     

Effect of body size, arm length, sex and temperature on somatosensory evoked potential latency

Beside the technical factors different biological factors contribute to the variability of the somatosensoric evoked potentials. In 30 volunteers the dependence of the latency of the spinal components N9, N13 (recorded at C7), of the cortical component N20 and of the interpeak interval N13-N20 from the body size and length of the arm was investigated. A significant dependence at the 1% level (p less than 0.001) was found for the latencies of N9, N13 and N20, whereas the interpeak interval N13-N20 was significant at the 5% level (p less than 0.05). Similarly in 20 further volunteers a significant dependence of the components N1, P1, N2, P2 and N3 from the body size at the 1% (p less than 0.001) after distal stimulation of the tibial nerve was observed. Using a covariance analysis it could be shown, that even after a body size correction, in females shorter latencies occur than in males. Furtheron we studied the effect of the temperature on the SSEP-latencies, by heating the upper and lower extremity stepwise from 31 degrees C to 37 degrees C using an infrared (DISA-Regler-System) lamp. As no significant dependence could be observed, we believe that the effect of temperature on latencies is so small, that in usual conditions no correction is needed. On the contrary a correction with body size or arm length is necessary, to avoid wrong positive or negative results.     

Reliability of late positive component activity (P3) in healthy elderly adults.

Auditory oddball paradigms (20% targets) were used to elicit components of the event-related brain potential in healthy, late middle-aged and elderly adults (N = 32) in two separate sessions approximately 4.5 months apart. Within each session data were acquired under two conditions: (a) 250 Hz standard, 500 Hz target; and, (b) 1000 Hz standard, 2000 Hz target. Measures of P3 latency and amplitude showed moderate to high reliability (.55 to .89) over the 4.5-month interval under both stimulus conditions using data acquired from the midline frontal (Fz), central (Cz), and parietal (Pz) sites. In the second session, latencies were prolonged in the 500 Hz target tone condition, and amplitudes tended to be reduced in the 2000 Hz target tone condition. These results suggest that P3 measures in studies of older adults are reliable over time, and the findings are discussed in conjunction with prior P3 reliability studies of younger adults.     

The repeat reliability of somatosensory evoked potentials

The test-immediate-retest reliability of latency and amplitude values of cervical and cortical somatosensory evoked potentials (SEP) to median nerve stimulation was assessed in 86 normal subjects aged 15 to 71 years. In addition to the stability of data between repeat trials within one test session the standard errors of measurement and the interpretable differences for SEP measures were calculated according to measurement theory. The study revealed retest correlations rtt greater than 0.80 for all latency measures of the cervical and cortical SEPs and all cortical amplitude parameters. The highest stability was found for the latency measures of the cervical components P10, N11, N13, the cortical components P16 and N20 and for the amplitude N20/P25.     

Vibrotactile threshold measurement for detecting peripheral neuropathy: defining variability and a normal range for clinical and research use

Aims/hypothesis We aimed to define normal ranges for vibration sense as measured by vibratory perception thresholds (VPTs) using biothesiometry. Methods We performed biothesiometry in a community-dwelling sample of 901 people aged 55 to 85 years who did not have diabetes. We quantitated the variation between repeat measures using analysis of variance and Bland–Altman plots. We also plotted the age- and sex-specific reference ranges. Results We found small but statistically significant differences between repeat measures using the ascending and descending method of limits. Statistically higher vibration thresholds were noted on the right arm and leg compared with the left. Significantly higher vibration thresholds were also seen in men vs women for both lower limbs. We also defined sex-specific reference intervals (normal ranges) for biothesiometry for older persons and quantitated the increase in vibration threshold with increasing age. Conclusions/interpretation For reliability, it may be sufficient to obtain the average of two ascending measures separated by at least 1 min in just the right hand or right foot, since this is usually the one with the higher threshold. Although identical reference ranges can be used for men and women for the upper limb, there are significant differences in the lower limbs. The major determinant of VPT is age: we have established age-specific norms for VPT testing for adults between 55 and 85 years of age.     

Somatosensory and visual evoked potentials in insulin-dependent diabetics with mild peripheral neuropathy

Using somatosensory and visual evoked potential techniques we have looked for evidence of central neuropathy in a group of insulin-dependent diabetics with mild peripheral neuropathy. The N9, N13, and N20 components of the somatosensory evoked potential were significantly (P less than 0.001) delayed in the diabetic group compared with the control subjects. There was a small but non-significant increase in the interpeak N13-9 and N20-13 latencies in the diabetic group. The visual evoked potential (P100) showed a small but insignificant delay. The delay in cerebral evoked potentials was mostly attributable to peripheral neuropathic damage and no firm evidence was obtained in favour of central diabetic neuropathy.     

Methods for assessing diabetic polyneuropathy: validity and reproducibility of the measurement of sensory symptom severity and nerve function tests

The usefulness of sensory symptoms in the assessment of diabetic polyneuropathy is unclear. In the present study, we studied the hypothesis that pain is associated with small nerve fibre function, and that sensory alteration is associated with large nerve fibre function. In addition, we assessed the reproducibility and the ability to detect changes in clinical status over time of the nerve function tests currently used in clinical trials. Patients (78) with stable diabetic polyneuropathy were examined on three separate occasions with a test-retest interval of 17 and 52 weeks. Small nerve fibre function was measured using temperature discrimination thresholds for warmth (TDTwarmth) and cold (TDTcold). Large nerve fibre function was measured by testing sensory and motor nerve conduction velocities (SNCV and MNCV) and vibration perception thresholds (VPT). Neuropathic pain was only significantly associated with TDTcold, and with the MNCV of the tibial nerve. Sensory alteration was associated with almost all nerve function tests except the SNCV and MNCV of the ulnar nerve. The measurements of symptom severity and the nerve function tests all proved to be sufficiently reproducible. The standardized smallest detectable difference on group level (SDD) of the measurement of sensory alteration and neuropathic pain were almost the same (9% and 12%, respectively). Among the nerve function tests, the SNCV and MNCV had the smallest SDD (3-4%), and were, therefore, potentially the most responsive instruments. The SDD of the TDT was greater than the VPT (9-14% vs 21-28%, respectively). In conclusion, neuropathic pain was not associated with small nerve fibre function, and sensory alteration was associated with both large and small fibre function. In addition, the standardized measurement of symptom severity, the SNCV and MNCV tests, and the VPT test appear to be useful for monitoring the course of polyneuropathy in clinical trials.     

The median nerve evoked potential in normal children and youths: normal values]

The derivation of cortical somatosensory evoked potentials permits a good local and functional diagnosis of supratentorial structures and the localisation of damage in this area. The special diagnostical relevance of early cortical somatosensory evoked potentials as a sage, non-invasive examination method in pediatric neurology is given both by these characteristics and by the fact that they cannot, in principle, be influenced by sleep or by drugs affecting the central nervous system. Somatosensory evoked cortical potentials of N. medianus were investigated for 35 children (17 boys, 18 girls) between the ages of 6 and 17, for whom there were no anamnestic or clinical indications of neurological or otological diseases. Investigations demonstrate that the SEPs of the N. medianus from the P15 up to and including the N55, is in every case clearly measurable in children from preschool age up to the end of adolescence. In the evaluation of the cortical SEPs, the P15, N20 and P25 were considered to be the components most stable and those most valuable for clinical practice. These could also be presented with the smallest standard deviations and side differences. The latencies of the P15 and N20 of the N. medianus show significant dependencies on the height of the children. The later potential components, side differences, interpeak intervals and amplitudes show no correlations with height. The SEPs of N. medianus show no dependencies on gender or on physical parameters such as weight or head circumference of the experiments. In summary it can be established that, using the procedure mentioned above, the cortical somatosensory evoked potentials in children can be described well and reproducibly and within practical narrow standard limits.     

Cortical somatosensory processing after botulinum toxin therapy in post-stroke spasticity

In dystonic and spastic movement disorders, abnormalities of motor control and somatosensory processing as well as cortical modulations associated with clinical improvement after botulinum toxin A (BoNT-A) treatment have been reported, but electrophysiological evidence remains controversial. In the present observational study, we aimed to uncover central correlates of post-stroke spasticity (PSS) and BoNT-A-related changes in the sensorimotor cortex by investigating the cortical components of somatosensory evoked potentials (SEPs). Thirty-one chronic stroke patients with PSS of the upper limb were treated with BoNT-A application into the affected muscles and physiotherapy. Clinical and electrophysiological evaluations were performed just before BoNT-A application (W0), then 4 weeks (W4) and 11 weeks (W11) later. PSS was evaluated with the modified Ashworth scale (MAS). Median nerve SEPs were examined in both upper limbs with subsequent statistical analysis of the peak-to-peak amplitudes of precentral P22/N30 and postcentral N20/P23 components. At baseline (W0), postcentral SEPs were significantly lower over the affected cortex. At follow up, cortical SEPs did not show any significant changes attributable to BoNT-A and/or physiotherapy, despite clear clinical improvement. Our results imply that conventional SEPs are of limited value in evaluating cortical changes after BoNT-A treatment and further studies are needed to elucidate its central actions.     

The electroneurophysiological evaluation of Rheumatoid Arthritis patients

In Rheumatoid Arthritis (RA), one clinical hallmark of the vasculitis is the appearance of neurological findings. However, it is often difficult to diagnose these slight or early neuropathies and the study of the peripheral neuromuscular system is often made difficult by symptoms resulting from pain in the joints, and limitations of movement. It is nevertheless often possible, by means of electroneuromyography to show objectively the existence and distribution of even subclinical neuropathies. In order to evaluate the neurophysiological functions of RA patients by means of the peripheral nerve conduction and somatosensory evoked potential studies, 33 RA patients and 20 healthy controls were included in this study. Two (6%) patients were found to have carpal tunnel syndrome, while 6 (18%) patients had mononeuritis multiplex. Delayed N12, N13, N1 and P1 latencies were detected in 6 (18%) of 33 RA patients suggesting central nervous system involvement with intact peripheral nervous system. Our results confirm earlier observations that symptoms of neuropathy are fairly common in cases of RA without there being any clear correlation with any clinical variable. Therefore, the inclusion of an electroneuro-physiologic examination of the RA patients is recommended in routine diagnostic procedure.