Comparison of Hoffmann reflex with quantitative assessment of cutaneous sensation in diabetic neuropathy

Neurophysiological studies of diabetic patients may show abnormalities even when clinical examination has revealed no sign of neuropathy. Quantitation of sensory function provides additional information when examining a patient with neuropathy. The value of the Hoffmann (H) reflex was investigated in diabetics who had undergone this examination. H-M intervals of the H-reflex, vibration perception thresholds (VPT's) and thermal discrimination thresholds (TDT's) were determined in 34 diabetics with clinical evidence of neuropathy and 16 diabetics without symptoms or signs of neuropathy. Normal values for VPT and TDT were obtained from the examination of 40 healthy subjects. The values of the H-M interval were significantly correlated with VPT's and not with TDT's. Three patients with clinical evidence of neuropathy and abnormal VPT's and TDT's had normal H-M intervals. For research purposes it is recommended that H-reflex studies are combined with the determination of sensory thresholds, but from a practical point of view determination of the H-M interval proved to be an effective tool for the investigation of neuropathy in diabetic patients.     

HIV neuropathy: an in vivo confocal microscopic study

Several approaches exist for quantitative assessment of human immunodeficiency virus (HIV)-associated distal sensory polyneuropathy (DSP). While useful, each has some limitations. This study evaluated non-invasive, in vivo reflectance confocal microscopy (RCM) of Meissner corpuscles (MCs) as a measure of HIV-DSP. Forty-eight adults (29 HIV-infected, 19 controls) underwent RCM of MC density (MCs/mm²) at the arch, fingertip, and thenar eminence (TE); ankle skin biopsy to measure epidermal nerve fiber density (ENFD); electrophysiologic studies; and tactile, vibration, and thermal threshold testing. HIV+ subjects were clinically categorized as having DSP signs or no signs. MC densities were lower in HIV+ subjects with DSP signs than in controls (arch, p?=?0.0003; fingertip, p?<?0.0001; TE, p?=?0.0002). Tactile thresholds in the TE and foot were worse in HIV-DSP than in controls, but in this mild DSP cohort, sural amplitudes, ENFD, and vibration and thermal thresholds did not differ significantly from controls. Fingertip MC densities and tactile thresholds at the foot were also lower in HIV+ subjects without DSP signs than in controls. Other sensory measures were not significantly different in HIV+ subjects without DSP signs than in controls. MC density correlated inversely with tactile thresholds at each imaging location. The results suggest that RCM of MC density complements existing sensory DSP measures and discriminates mild HIV-DSP from controls at a stage when sural amplitudes do not. Further studies are required to determine whether RCM of MC density can establish quantitative changes in DSP, in response to treatment or disease progression.     

Correlation and cluster analysis of sensory, pain, and reflex thresholds to various stimulus modalities in symptom-free subjects.

OBJECTIVE: In order to evaluate the possible relation between the psychophysical response and a motor reflex, sensory and pain thresholds to various stimuli were analyzed in combination with the occurrence threshold of the late masseteric exteroceptive suppression (ES2) period. METHODS: Twenty men and 20 women participated. The tactile detection threshold and the filament-prick pain detection threshold were measured on the cheek skin overlying the left masseter muscles. The pressure pain threshold and pressure pain tolerance threshold were measured at the left masseter muscle. The surface EMG was recorded from the left masseter muscle, while electrical stimuli with 13 fixed intensities were applied to the skin above the left mental nerve. The stimulation intensity at which the ES2 appeared for the first time and the lowest stimulus intensity at which the subjects reported to be painful were defined as the ES2 and pain threshold, respectively. RESULTS: There were significant positive correlations between the tactile detection threshold and the pain thresholds determined using the different stimulus modalities, and the ES2 threshold was also significantly correlated with the pain thresholds (P<0.05). Cluster analysis could significantly discriminate two distinct groups with high versus low tactile, pain and ES2 thresholds (P<0.05). CONCLUSIONS: The present findings suggested that the ES2 reflex response has a relation with the individual sensory and pain sensitivity in symptom-free subjects. SIGNIFICANCE: Combined examination of sensory, pain, and ES2 thresholds might provide complementary information on the pathophysiology underlying orofacial pain.     

Spontaneous pain, pain threshold, and pain tolerance in Parkinson��s disease

The mechanisms underlying pain in Parkinson's disease (PD) are unclear. Although a few studies have reported that PD patients may have low pain threshold and tolerance, none could accurately assess whether there was a correlation between sensory thresholds and demographic/clinical features of PD patients. Thus, tactile threshold, pain threshold, and pain tolerance to electrical stimuli in the hands and feet were assessed in 106 parkinsonian patients (of whom 66 reported chronic pain) and 51 age- and sex-matched healthy subjects. Linear regression models determined relationships between psychophysical parameters and demographic/clinical features. Female gender, severity of disease, medical disease associated with painful symptoms, and dyskinesia were more frequently observed in PD patients experiencing pain, even though dyskinesia did not reach significance. Pain threshold and pain tolerance were significantly lower in PD patients than in control subjects, whereas the tactile threshold yielded comparable values in both groups. Multivariable linear regression analyses yielded significant inverse correlations of pain threshold and pain tolerance with motor symptom severity and Beck depression inventory. Pain threshold and pain tolerance did not differ between PD patients with and without pain. In the former group, there was no relationship between pain threshold and the intensity/type of pain, and number of painful body parts. These findings suggest that pain threshold and pain tolerance tend to decrease as PD progresses, which can predispose to pain development. Female gender, dyskinesia, medical conditions associated with painful symptoms, and postural abnormalities secondary to rigidity/bradikinesia may contribute to the appearance of spontaneous pain in predisposed subjects.     

Normal distributions of thermal and vibration sensory thresholds

The distributions of sensory thresholds were estimated in a healthy population while controlling for potential covariates. Using the method of levels and the two-alternative forced choice, thermal and vibration thresholds respectively were measured in the hand and foot of 148 subjects. Age was uniformly distributed between 20 and 86 years. Independent effects of age, gender, height, and skin temperature were estimated using multiple linear regression. Parametric and nonparametric methods were used to estimate the distributions of interest. Significant age-related increases were observed for all vibration thresholds (P < 0.0001), and for thermal thresholds in the foot (P < 0.0002). Percentiles were estimated for thermal thresholds in the hand and age-adjusted continuous distributions were calculated for all other thresholds. Height was positively associated with vibration thresholds in the foot (P < 0.003), and appropriate corrections were made. Our results provide reference values for thermal and vibration sensory thresholds in a healthy population, allowing for the accurate diagnosis of disordered sensory function. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:367–374, 1998.     

Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease

Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired‐pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1–7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired‐pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment. © 2011 Movement Disorder Society     

Foot sole skin temperature affects plantar foot sensitivity

ObjectiveFactors like age and polyneuropathic diseases are known to influence foot sensitivity and are considered when applying quantitative sensory testing. However, the effects of temperature on foot sensitivity are controversial. Therefore, the aim of this study was to investigate the influence of different foot sole temperature on vibration sensitivity of healthy subjects.MethodsForty healthy subjects (20 male, 20 female) were analyzed. Vibration thresholds were measured at three anatomical locations (Heel, 1st Metatarsal Head and Hallux) of both feet at 200 Hz. Thresholds were measured at initial baseline temperature and after cooling/warming of the foot skin 5–6 °C. Comparisons between baseline and cooled/warmed thresholds as well as between genders were performed.ResultsThere were no significant differences in vibration thresholds when comparing men and women. Thresholds were significantly higher after skin cooling for at all anatomical locations. After skin warming, thresholds were significantly lower at all measured anatomical locations.ConclusionsSmall temperature changes significantly influence vibration sensitivity of healthy subjects and should be controlled during collection of foot sensitivity data.SignificanceThe control of temperature is an important factor to enhance the quality of data acquired with quantitative sensory testing.     

The extent of small fibre sensory neuropathy in diabetics with plantar foot ulceration.

Thresholds for cutaneous warming and cooling stimuli were measured in 20 diabetics with neuropathic foot ulcers. All patients had a profound disturbance of sensory perception in the ulcerated foot with complete loss of perception of warming; thresholds for vibration and cooling were highly abnormal in all but two patients. Measurements of thermal threshold were made on both feet in 10 patients: warming was lost bilaterally in all, and cooling was bilaterally absent in six. There was no clear pattern of sensory loss in those diabetics with unilateral foot ulceration to suggest that sensory impairment was the determining factor for the development of a plantar ulcer. Measurements of thermal thresholds were made at additional sites in 13 patients and although the most marked abnormalities of sensation were always found in the feet, in some severe neuropaths, abnormal thresholds on the hand and even the face were demonstrated. Thresholds for warming were invariably more abnormal than thresholds for cooling. The diabetics with neuropathic ulceration in this study all had severe generalised peripheral nerve disease involving large myelinated as well as both small myelinated and unmyelinated sensory fibres. The quantitative evidence on the distribution of sensory loss for thermal sensations supports the hypothesis that the neuropathic process affecting the small myelinated and unmyelinated fibres is length dependent.     

Quantitative assessment of cutaneous thermal and vibration sensation and thermal pain detection thresholds in healthy children and adolescents

Quantitative sensory testing (QST) is a noninvasive, computer-assisted method for assessing function in peripheral small and large sensory fibers. In order to use QST for clinical neurological assessment in children, it is necessary: (1) to determine whether children can reliably perform these tests and (2) to characterize normal ranges in healthy children. Values of cold sensation, warm sensation, cold pain, heat pain, and vibration sensation detection thresholds were determined in the hand and foot with the method of limits (MLI) and method of levels (MLE) in 101 healthy children aged 6-17 years using a commercially available device. Both MLI and MLE were well-accepted by children, and there was good reproducibility between two sessions. The MLE takes longer to perform but produces lower thermal detection thresholds than the MLI. In the MLI, vibration and warm sensation showed higher thresholds in the foot than hand, whereas cold pain showed lower thresholds in the foot than hand. Based on these results, QST may be used to document and monitor the clinical course of sensory abnormalities in children with neurological disorders or neuropathic pain.     

Spatial attentional shifts: further evidence for the role of polysensory mechanisms using visual and tactile stimuli

Normal subjects performed simple reaction time responses to lateralized visual target stimuli (Experiment 1) and lateralized tactile target stimuli (Experiment 2). In each experiment, the lateralized targets were preceded at one of four intervals by a visual or tactile cue located on the same (valid cue), or opposite (invalid cue) side, or on both sides (neutral cue). The validity of the visual and tactile cues influenced the speed of response to either target stimulus. These findings, together with those previously reported (Buchtel and Butter, Neuropsychologia 26, 499-509, 1988), are consistent with the view that intra- and inter-modal spatial cueing is effective with modalities that are linked to orienting systems in which movements of the sensory array serve to improve sensory analysis.     

Weighted needle pinprick sensory thresholds: a simple test of sensory function in diabetic peripheral neuropathy.

A simple device is described, consisting of 12 weighted 23 gauge disposable needles (0.2 to 5.2 g), for testing sensation in busy diabetic clinics. The pinprick sensory threshold (PPT) is the lightest weighted needle which consistently elicits a sharp sensation. The subjects were 48 healthy controls (hospital staff), 44 diabetic patients without neuropathic symptoms, and 35 diabetic patients with chronic painful neuropathy. In the controls, the mean PPT from the right hand and foot obtained on two test occasions a week apart did not differ significantly. In diabetic patients without symptomatic neuropathy, the mean PPT in the right hand and right foot were significantly higher than in the controls. The diabetic patients with painful neuropathy had clearly increased mean PPT in the right hand and foot compared with controls. Marstock thermal limen in diabetic patients with painful neuropathy correlated significantly with PPT determinations. PPT and thermal thresholds probably give comparable information on small fibre dysfunction in diabetic patients with symptomatic neuropathy. Compared with thermal threshold determinations however, the weighted needle apparatus is inexpensive, simple, and rapid to use.     

Sensory sensitivity to external stimuli in Tourette syndrome patients

Patients with Tourette Syndrome often state that their sensitivity to sensations is equally or more disruptive than are motor tics. However, their sensory sensitivity is not addressed by standard clinical assessments nor is it a focus of research. This lapse likely results from our limited awareness and understanding of the symptom. In this study (1) we defined the patients' experience of sensitivity to external stimuli in detail, and (2) we tested 2 hypotheses regarding its origin. First, we interviewed in depth and administered a lengthy questionnaire to adult Tourette patients (n = 19) and age‐matched healthy volunteers (n = 19). Eighty percent of patients described heightened sensitivity to external stimuli, with examples among all 5 sensory modalities. Bothersome stimuli were characterized as faint, repetitive or constant, and nonsalient, whereas intense stimuli were well tolerated. We then determined whether the sensitivity could be the result of an increased ability to detect faint stimuli. After measuring the threshold of detection for olfactory and tactile stimuli among the patients and healthy volunteers, we found no significant differences between them for either sensory modality. These results indicate that patients' perceived sensitivity derives from altered central processing rather than enhanced peripheral detection. Last, we assessed one aspect of processing: the perception of intensity. When subjects rated the intensity of near‐threshold tactile and olfactory stimuli, there was a surprising difference: Tourette patients more frequently used the lowest range of the scale than did healthy volunteers. Future research is necessary to define the anatomical and physiological basis of the patients' experience of heightened sensitivity. © 2011 Movement Disorder Society     

Detection threshold for percutaneous electrical stimuli: asymmetry with respect to handedness.

Sensory strength-duration curves were obtained using percutaneous true square-wave pulses ranging from 0.1 to 20.0 ms produced by an isolated constant current stimulator. In 119 healthy volunteers sensory thresholds were measured bilaterally by stimulating the distal phalange of the little finger. In order to examine the relationship of sensory threshold and handedness the latter was assessed by means of the Edinburgh Inventory. An asymmetry of sensory threshold was found for all the subjects and this was more pronounced with shorter stimuli. Of right-handers tested 73.5% had a lower threshold on the left side while 70.8% of left-handers had a lower threshold on the right side. Although threshold asymmetry is associated with handedness this is not necessarily due to cerebral lateralization.     

Vibration disappearance threshold may be raised by measuring it

The influence of duration and intensity of the initial level of vibration on vibration perception threshold was studied in 15 healthy young subjects (aged 27.9 ± 7.6 years) with a Vibrameter (Somedic AB Sweden).

The threshold for increasing vibration corresponded well to the normal values published by the manufacturer. The thresholds for decreasing vibration were measured with three different starting conditions: starting from a low level of vibration, a high level, and from a low level sustained for one minute. Higher intensity and longer duration of the initial vibration raised the disappearance threshold significantly. Vibration disappearance thresholds can be influenced by measuring them. As a result, the investigation of the vibration sense calls for strict control over intensity and duration of the stimuli.     

Sensory temporal thresholds and interhemispheric transfer times in multiple sclerosis: a preliminary study of a new outcome measure

This preliminary study investigated the potential of a cerebral lateralization technique that measures both, temporal judgements to sensory stimuli and interhemispheric transfer time (IHTT), as an outcome measure in multiple sclerosis (MS). Tactile stimulation was delivered to one or both hands by mechanical tactile stimulators. Pairs of light emitting diodes were presented to hemifields for visual stimulation. Response consisted of a binary forced-choice (YES/NO) judgement as to the simultaneity of the onset of pairs of stimuli. Both tactile and visual temporal thresholds were significantly higher in MS patients than controls in every presentation condition. IHTT estimates (threshold differences between unilateral and bilateral presentations) for the tactile and visual tasks were also significantly longer in patients than controls. Age correlated with sensory temporal thresholds for the control group only. These findings suggest that this technique may be a useful outcome measure in MS. We hypothesize that myelin injury slows central conduction therefore impairing the ability to judge the onset of sensory stimuli and increasing IHTTs.     

An improved automated method for the measurement of thermal thresholds. 1. Normal subjects.

Clinical tests of thermal sensation are poorly quantified and not strictly modality specific. Previous automated thermal testing systems have had limited usefulness with high intra-and inter-individual variability. This paper describes an automated thermal system (Glasgow system) which is an extensive modification of previous techniques to answer these criticisms. It comprises a microprocessor-driven Peltier element and utilises the forced choice method of psychophysical analysis to determine the thresholds to thermal stimulation. In a control group of 106 healthy subjects the mean heat threshold for the wrist was found to be 0.23 degree C (SD = 0.06 degree C) and the mean cold threshold 0.15 degree C (SD = 0.05 degree C). Repeated determinations showed a maximum of 5% intra-individual variation in comparison to previously reported values of up to 150%.     

Sensory Temporal Thresholds and Interhemispheric Transfer Times in Multiple Sclerosis: A Preliminary Study of a New Outcome Measure

This preliminary study investigated the potential of a cerebral lateralization technique that measures both, temporal judgements to sensory stimuli and interhemispheric transfer time (IHTT), as an outcome measure in multiple sclerosis (MS). Tactile stimulation was delivered to one or both hands by mechanical tactile stimulators. Pairs of light emitting diodes were presented to hemifields for visual stimulation. Response consisted of a binary forced-choice (YES/NO) judgement as to the simultaneity of the onset of pairs of stimuli. Both tactile and visual temporal thresholds were significantly higher in MS patients than controls in every presentation condition. IHTT estimates (threshold differences between unilateral and bilateral presentations) for the tactile and visual tasks were also significantly longer in patients than controls. Age correlated with sensory temporal thresholds for the control group only. These findings suggest that this technique may be a useful outcome measure in MS. We hypothesize that myelin injury slows central conduction therefore impairing the ability to judge the onset of sensory stimuli and increasing IHTTs.     

Large and small fibre type sensory dysfunction in patients with cancer.

Quantitative sensory testing was used to assess the prevalence of sensory dysfunction in patients with cancer, carefully screened for other risk factors for neuropathy. Large fibre type sensory function was evaluated using vibration threshold (VT) determinations while small fibre type sensory function was assessed by thermal threshold (TT) determinations. Mean VT and TT were significantly elevated in the toes but not the fingers of cancer patients. VT elevations in the toes occurred in 31% of cancer patients and in 6% of control subjects. TT elevations in the toes occurred in 43% of cancer patients and 4% of control subjects. Based on these findings it is concluded that large and small fibre type sensory dysfunction is much more common in carefully screened cancer patients than in control subjects. This sensory dysfunction is most likely to represent a neuropathy related directly or indirectly associated with cancer.     

Direct current stimulation over the human sensorimotor cortex modulates the brain's hemodynamic response to tactile stimulation

Tactile stimuli produce afferent signals that activate specific regions of the cerebral cortex. Noninvasive transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. We therefore hypothesised that a single session of tDCS targeting the sensory cortices would alter the cortical response to tactile stimuli. This hypothesis was tested with a block‐design functional magnetic resonance imaging protocol designed to quantify the blood oxygen level‐dependent response to controlled sinusoidal pressure stimulation applied to the right foot sole, as compared with rest, in 16 healthy young adults. Following sham tDCS, right foot sole stimulation was associated with activation bilaterally within the precentral cortex, postcentral cortex, middle and superior frontal gyri, temporal lobe (subgyral) and cingulate gyrus. Activation was also observed in the left insula, middle temporal lobe, superior parietal lobule, supramarginal gyrus and thalamus, as well as the right inferior parietal lobule and claustrum (false discovery rate corrected, P < 0.05). To explore the regional effects of tDCS, brain regions related to somatosensory processing, and cortical areas underneath each tDCS electrode, were chosen as regions of interest. Real tDCS, as compared with sham tDCS, increased the percent signal change associated with foot stimulation relative to rest in the left posterior paracentral lobule. These results indicate that tDCS acutely modulated the cortical responsiveness to controlled foot pressure stimuli in healthy adults. Further study is warranted, in both healthy individuals and patients with sensory impairments, to link tDCS‐induced modulation of the cortical response to tactile stimuli with changes in somatosensory perception.     

Quantitative Sensory Testing in adults with Tourette syndrome

IntroductionAbnormal sensory perceptions, for instance hypersensitivity to certain external stimuli or premonitory urges preceding tics, are core features in Gilles de la Tourette syndrome (GTS). Aberrant awareness of externally applied stimuli in terms of altered sensory perception thresholds might contribute to these sensory phenomena in GTS.MethodsWe used the well-established and standardized “Quantitative Sensory Testing” (QST) battery (German Research Network on Neuropathic Pain) to investigate 13 sensory parameters including thermal, mechanical/tactile and pain thresholds in 14 GTS patients without clinically significant comorbidities and 14 healthy controls matched for age and gender.ResultsThere were no relevant group differences in any of the 13 QST parameters and no specific QST pattern in GTS patients. There was no correlation between QST parameters and “Premonitory Urge for Tics scale” (PUTS) scores.ConclusionOur data show that the perceptual threshold detection of externally applied sensory stimuli is normal in adults with GTS. This indicates that other perceptual mechanisms, such as abnormal central sensorimotor processing and/or aberrant interoceptive awareness might underlie the clinically significant sensory abnormalities in GTS.