Large Fiber Function Research Articles

Are there two types of diabetic foot ulcers?

Neurological function was determined in diabetic patients with peripheral vascular disease and foot ulcers ( n = 13). This was compared to that of diabetic patients without foot ulcers with ( n = 23) and without ( n = 13) symptoms of neuropathy. Diabetic patients with typical neuropathic ulcers ( n = 13) and age-matched healthy controls ( n = 20) were also studied. The beat-to-beat variation with deep breathing was 6.1 ± 1.0 beats/min in those with peripheral vascular disease and foot ulcers, less than 50% of that of diabetic patients without foot ulcers ( p < 0.01) or normal controls ( p < 0.005). Autonomic surface potentials in the soles were greatly diminished or absent in nearly all the patients with peripheral vascular disease and ulcers. Quantitative sensory testing revealed profound abnormalities in small fiber (heat and cold sensation) and large fiber (vibration sensation) function in diabetic patients with peripheral vascular disease and foot ulcers. Our results document the presence of advanced autonomic and somatosensory neuropathy in nearly all diabetic patients with peripheral vascular disease and foot ulcers.

Use and misuse of conventional electrodiagnosis, quantitative sensory testing, thermography, and nerve blocks in the evaluation of painful neuropathic syndromes.

A number of laboratory tests are critically important in the quest to diagnose presence or absence of organic neuropathic dysfunction and to establish the relevance of such to the subjective pain complaints. However, none of these tests has absolute diagnostic value and their results must be interpreted in the light of the clinical picture. Conventional electrophysiology evaluates function of large caliber afferent and motor fibers leaving the function of small caliber afferent fibers unexplored, and cannot explore the basis for positive sensory phenomena. The quantitative somatosensory thermotest is the best test available to explore function of small caliber afferents. It allows documentation of positive sensory phenomena in the form of thermal hyperalgesia. Because it is a psychophysical test, it lacks localizing value. Thermography sensitively detects and precisely delineates areas of cutaneous thermal change of neural origin. Three types of diagnostic neurologic blocks are used in the clinic: compression-ischemia, local anesthetic and sympathetic blocks. Although they may provide important information about the pathophysiology of pain and hyperalgesias, adequate placebo control is of the essence because chronic neuropathic pain patients may express a high incidence of placebo response.

The function of large and small nerve fibers in renal failure

Previous clinical and neurophysiological studies of uremic neuropathy have focused almost exclusively on the function of large sensory and motor axons. The sensations of heat and cold depend on the function of unmyelinated afferents and small myelinated afferents, respectively, and these sensations can be quantified using a standardized psychophysical technique. Thermal thresholds were measured in 20 patients with end-stage renal failure to determine the extent of small afferent fiber involvement and to compare this with the clinical and electrophysiological evidence of large fiber involvement. Whereas abnormalities of standard nerve conduction studies were found in 16 patients, abnormal thermal thresholds were found in only 6 patients. In the nerve conduction studies, the amplitudes of nerve potentials were reduced more than their conduction velocities, consistent with an axonopathy. This study found little evidence of significant dysfunction of small afferent fibers in end-stage renal failure and, when such changes occurred, they did not correlate with the clinical evidence of polyneuropathy. The functional sparing of axons of small diameter is consistent with the relative sparing of these axons in pathological studies.

Somesthetic and Electrophysiologic Effects of Topical 0.025% Capsaicin in Man

As a topical agent, capsaicin reportedly blocks pain without otherwise impairing sensation. Ten subjects underwent blinded, multiple-dose application of topical 0.025% capsaicin or control emollient to skin test sites in order to evaluate capsaicin effectiveness and toxicity. Clinical changes in somesthetic perception of pinprick, heat and cold developed, but neurogenic flare responses were unchanged. Clinical and electrophysiologic measures of large fiber and autonomic function were unaffected by capsaicin. This study indicates that 0.025% capsaicin is a safe topical agent with demonstrable clinical effects on small fiber function but not on large fiber or autonomic function.

Somesthetic and electrophysiologic effects of topical 0.025% capsaicin in man.

As a topical agent, capsaicin reportedly blocks pain without otherwise impairing sensation. Ten subjects underwent blinded, multiple-dose application of topical 0.025% capsaicin or control emollient to skin test sites in order to evaluate capsaicin effectiveness and toxicity. Clinical changes in somesthetic perception of pinprick, heat and cold developed, but neurogenic flare responses were unchanged. Clinical and electrophysiologic measures of large fiber and autonomic function were unaffected by capsaicin. This study indicates that 0.025% capsaicin is a safe topical agent with demonstrable clinical effects on small fiber function but not on large fiber or autonomic function.

Current perception thresholds: a new, quick, and reproducible method for the assessment of peripheral neuropathy in diabetes mellitus

The Neurometer is a variable constant current sine wave stimulator, and has recently been proposed as a simple non-invasive and quantitative measure of peripheral nerve function. The device is portable and battery operated; assessment of upper and lower extremities takes only a few min, in contrast to conventional assessment techniques. In order to assess its potential in the quantification of diabetic neuropathy, detection thresholds for constant current electric sine wave stimulation were measured at three different frequencies in different sites in 31 healthy control subjects and 90 diabetic patients with and without neuropathy. The device provides good discrimination between neuropathic and non-neuropathic groups (p less than 0.001) and is quick and easy to use. Comparisons with results of conventional tests of nerve function show that high frequency detection thresholds correlate best with tests of large fibre function (r = 0.42-0.69, p less than 0.001), and low frequency detection thresholds correlate with tests of small fibre function (r = 0.34-0.46, p less than 0.005). It is concluded that the device may be a simple and comprehensive way of assessing peripheral nerve function.

Evaluation of thermal, pain, and vibration sensation thresholds in newly diagnosed type 1 diabetic patients.

Small and large fibre function was studied in 40 non-ketotic, newly diagnosed Type 1 diabetic patients and 48 age-matched controls, using 12 quantitative tests for assessment of cutaneous sensation. Patients were aged 10-39 years and had been treated with insulin for 4-31 days. Thermal discrimination (foot), warm and cold thermal perception (thenar eminence and foot), and heat and cold pain perception thresholds (thenar eminence) were significantly elevated in the patients as compared with the controls (p less than 0.05 to p less than 0.001). No significant differences in thermal discrimination (thenar), heat and cold pain perception (foot), and metacarpal as well as malleolar vibration perception thresholds were noted between the groups. The rates of abnormalities among the individual tests ranged from 0% to 27.5%, being lowest for vibration perception and highest for thermal perception thresholds after cold stimuli. The results in nine of 12 tests correlated significantly with age, but only two were related to HbA1c. Thus, sensory neural functions transmitted by small fibres, but not those transmitted by large fibres, were impaired in newly diagnosed Type 1 diabetics after the correction of initial ketosis and hyperglycaemia. Cooling perception tests were most sensitive in detecting abnormality. An age-related involvement of different small fibre functions was present in these patients.

Assessment of small and large fiber function in long-term type 1 (insulin-dependent) diabetic patients with and without painful neuropathy

Twelve neural function tests (thermal discrimination thresholds, pain perception thresholds to heat and cold stimuli, vibration perception thresholds, and motor and sensory nerve conduction velocities) were assessed in the lower and upper extremities of 60 long-term type 1 diabetic patients. Thirty patients were asymptomatic (group 1) and 30 patients had painful neuropathy (group 2), predominantly originating in the distal lower limbs (group 2a; n = 20) or in the distal upper limbs (group 2b; n = 10). There were no significant differences between the groups with regard to age, duration of diabetes or glycemic control. Eleven of the 12 functions tested (6 in lower and upper limbs, respectively) were significantly diminished in both groups of diabetics as compared to age-matched control subjects. Group 2a had significant impairment in 5 of 6 parameters of the lower limbs, while in group 2b only 1 of 6 functions of the upper limbs was diminished. In the whole diabetic group, the most frequent abnormality was an elevated threshold for thermal sensation in the foot. Significant correlations between small and large fiber abnormalities were observed predominantly in the foot. Selective affection of small or large fiber functions showed different patterns in the arms and in the legs. In the upper extremities selective impairment in nerve conduction was predominant, while in the lower extremities it was thermal sensation. These findings suggest that both generalized and selective small or large fiber affection may occur in long-term type 1 diabetic patients. Dysfunction of both modalities is more severe in the lower limbs, when painful symptoms have developed in this region.

Small- and large-fiber involvement in early diabetic neuropathy: a study with the medial plantar response and sensory thresholds.

Small- and large-fiber function in diabetic neuropathy was studied in 68 patients (mean age 45.4 +/- 12.9 yr; 27 type I and 41 type II diabetics) with psychophysical tests of vibration and thermal sensation and neurophysiological measurements, including the medial plantar sensory action potential (MPSAP). Thermal sensitivity at the dorsolateral aspect of the foot (Pfizer thermal tester) correlated significantly with vibration thresholds (Somedic vibrameter) at three sites in the foot and two in the hand. Forty patients had normal sensory thresholds, but 18 of these lacked an MPSAP. Smaller groups had a single abnormal sensory threshold: 12 (18%) had an abnormal vibration threshold, and 24 (35%) had abnormal thermal sensitivity; 8 of the former group and 17 of the latter group lacked an MPSAP response. Only 8 (12%) had both abnormal vibration and thermal sensation (6 without an MPSAP). Fifteen of the 17 symptomatic patients had lost the MPSAP, but there was no consistent pattern of sensory loss. In this relatively young group of diabetics, more patients showed absent MPSAP responses than an abnormality in either sensory test on its own. The MPSAP is frequently absent in patients with no abnormalities in psychophysical tests of peripheral large-fiber function (vibration sensation) and small-fiber function (thermal sensitivity).