Paradoxical shortening of sympathetic skin response latency at distal recording sites

ObjectiveThe purpose of this study was to investigate and to discuss the neurophysiological mechanism of paradoxical shortening of the sympathetic skin response (SSR) latency at distal recording sites.MethodsThe latency and peak-to-peak amplitude of SSRs evoked by magnetic stimuli were analyzed. Eight active electrodes were placed on the palmar (anterior) and dorsal (posterior) sides of the hand (forearm) proximal to the distal arrangement.ResultsSSRs from two palm sites had significantly shorter latencies and larger amplitudes than the SSRs at the other six sites, including the proximal sites of the forearm.ConclusionsThis finding indicated that the SSR latency at different sites was not linearly prolonged as the distance of the recording sites from the proximal to distal areas increased. The paradoxical shortening of the latency and the large amplitude of the SSR from the palm can be explained by a recent model of the equivalent current dipole caused by the Na+ concentration gradient. The high density of sweat glands in the palm possibly produced the present findings.SignificanceWe should carefully interpret the sudomotor conduction velocity derived from latency difference between two sites, especially for thermal and emotional sweating.     

Influence of stimulus intensity on waveform of sympathetic skin response evoked by magnetic stimulation.

OBJECTIVE: The aim of this study was to investigate the influence of stimulus intensity on the waveform of sympathetic skin response (SSR). The origin of the SSR waveform was discussed. METHODS: A total of 12 SSRs from palm skin were analyzed in 40 normal subjects. SSR was evoked by magnetic stimulation to the neck at 3 different intensities (10, 35, and 70% of the maximum output). The 3 stimuli were repeatedly applied in 4 separate sets. Waveforms were classified as either the P type, in which the positive component was larger than the negative one, or the N type, in which the negative component was larger than the positive one. Amplitude values of peak-to-peak, the first negative (N1), and subsequent positive (P1) components were compared among the 12 responses. RESULTS: When the stimulation was increased, the SSR size became larger. The P type SSR was most frequently found in the maximum stimulation. Strong stimulation generally produced a large P1. Only the N type SSR exhibited a large N1 response to the maximum stimulation. There was a significant, negative correlation between N1 peak duration (difference between the SSR onset and N1 peak latencies) and P1 amplitude. CONCLUSIONS: These results suggested that strong responses probably produced a P type SSR with a large P1 component. In this condition, a rapid change of potential from negative to positive prevented any correlation between N1 amplitude and the magnitude of the response. In the N type SSR, however, a large N1 was associated with a strong response. These findings can be explained by a newly presented theory on the neurophysiological origin of the negative and positive components, based on a model of equivalent current dipole dependent on the Na+ concentration gradient. SIGNIFICANCE: The present study provided some suggestions on the neurophysiological mechanism of SSR waveform.     

Cutaneous silent period in hand muscle is evoked by laser stimulation of the palm, but not the hand dorsum

Painful electrical stimulation of the fingers evokes an inhibitory response in hand muscles (cutaneous silent period, CSP). The aim of this study was to determine whether purely nociceptive thermal stimuli applied to the hand evoke a CSP. High-intensity laser pulses (205 +/- 44 mJ) were delivered to the dorsum and palm of the hand in five volunteers. Electromyographic signals were recorded from the ipsilateral first dorsal interosseous muscle. We then compared the laser-evoked CSP with the CSP induced by electrical stimulation. A clear laser CSP (latency 90 +/- 7 ms) was evoked in all subjects when laser pulses were applied to the palm of the hand, whereas no response was recorded after stimulation of the dorsum. Electrical stimulation of both the dorsum and the palm evoked a CSP (latency 65 +/- 5 ms), although the reflex threshold was significantly lower after stimulation of the palm. This study confirms that the CSP is a nociceptive response specific to limbs that grasp. In humans, palm nociceptors are probably more functionally effective than dorsal nociceptors in inducing the hand-muscle inhibition that interrupts hand prehension (so that a potentially noxious source is dropped) before proximal muscles withdraw the limb.     

Sympathetic skin response in myelopathies

Autonomic dysfunctions cause significant morbidity and mortality among patients with spinal cord disorders. Sympathetic skin response (SSR), a simple, noninvasive electrophysiological technique, may be useful for assessing sympathetic functions in patients with myelopathies. Our aim was to study SSR in patients with myelopathy and correlate it with clinical features, severity of the impairment, somatosensory evoked potentials. and outcome. Thirty patients (15 men, 15 women) 12 to 60 years old with myelopathies of different etiology were studied. Subjects with clinical, electrophysiologic, or radiologic evidence of lesions outside the spinal cord were excluded. Somatosensory evoked potentials (SSEP) were recorded from scalp with median nerve stimulation at the wrist and posterior tibial nerve below the medial malleolus. The SSR was recorded from palm and sole after stimulating the supraorbital nerve at forehead, median nerve at wrist, and posterior tibial nerve below medial malleolus. The SSR was considered abnormal when absent. The sites of the lesions in these patients were cervical (13), thoracic (16), and lumbar (1). The lesion was clinically complete in six patients. Good motor recovery was noted in 16 subjects. SSR was absent from sole in 25 and palm in 10 patients from all three sites of stimulation. In addition, three patients also had absent SSR from palm on posterior tibial nerve (PTN) stimulation. SSEP was absent from median (N₁₉) in three and posterior tibial (N₃₉) in 20 patients. Among 10 patients with absent SSR from palm, only three had a good outcome. Presence of SSR from palm to PTN stimulation correlated with sparing of bladder sensations and good outcome. However, absent SSR from sole did not correlate with clinical features, bladder dysfunction, or outcome.Sympathetic skin response is frequently abnormal in patients with myelopathies. Spinal afferent and efferent tracts for SSR are different and may be affected individually. The afferent pathways are closely related to tracts conveying bladder sensation. Preserved palmar SSR on PTN stimulation may suggest good motor outcome. SSR may be a valuable adjunct in evaluating patients with myelopathies.     

Characteristics of habituation of the sympathetic skin response to repeated electrical stimuli in man.

OBJECTIVES: To study the effect of repeating electrical peripheral nerve stimulation on latency, duration and amplitude of the sympathetic skin response (SSR). METHODS: SSRs were elicited in all limbs by median and peroneal nerves stimuli. In 10 subjects, 20 stimuli were applied at random time intervals (15-20 s). Another test was performed in 7 subjects using the same protocol, but switching the stimulation site every 5 or 10 stimuli without warning. RESULTS: The mean amplitude of right palmar response to right peroneal nerve stimulation decreased from 5.05+/-0.76 (SEM) mV at the first stimulus to 1.23+/-0.42 mV at the 20th stimulus (P<0.001). The latency did not change significantly (1473+/-82 to 1550+/-90 ms, P>0.1), while the duration increased (1872+/-356 to 3170+/-681 ms, P<0.001). Stimulation and recording at other sites showed similar trends. Changing the stimulation site failed to alter the adaptation process in terms of amplitude, latency or duration. CONCLUSIONS: Changes in amplitude and duration of the SSRs to repeated electrical stimuli can occur in presence of constant latency and appear to be independent of the source of sensory input. Peripheral sweat gland mechanisms may be involved in the loss of amplitude and increase in duration of the SSR during habituation.     

Excitability recovery curve of the sympathetic skin response in healthy volunteers and patients with palmar hyperhidrosis.

OBJECTIVES: Patients with primary palmar hyperhidrosis (PPH) might exhibit hyperexcitability of the reflex circuits involved in sweating. We hypothesized that this hyperexcitability could become evident in the study of the excitability recovery curve of the sympathetic sudomotor skin response (SSR). METHODS: In 10 patients with PPH and 10 healthy volunteers used as control subjects, we recorded the SSR in the palm of the right hand to pairs of median nerve electrical shocks separated by inter-stimuli intervals (ISIs) ranging from 0.5 to 3.5 s. The amplitude of the SSR generated by the second stimulus (SSR2) was expressed as a percentage of that generated by the first (SSR1), and compared between control subjects and patients for each ISI. RESULTS: None of the control subjects showed a recovery of the SSR for ISIs of 1.5 s or less. On the contrary, patients showed a statistically significant enhancement of the SSR excitability recovery curve, with onset of recovery at 1.5 s in 5 patients. Two patients showed a double peak response to single electrical stimulation and were not considered in the calculation of the SSR recovery curve. Mean excitability recovery percentages were larger in patients than in control subjects at ISIs of 2, 2.5 and 3 s. CONCLUSIONS: The enhancement of the SSR recovery curve in patients with PPH suggests hyperexcitability of the somatosympathetic polisynaptic pathway involved in sweating. This could partly underlie the pathophysiology of PPH.     

Comparison of sympathetic sudomotor and skin responses in alcoholic neuropathy

We evaluated sympathetic sudomotor and parasympathetic vagal function in 30 chronic alcoholic patients and 28 control subjects by means of silicone imprints, sympathetic skin responses (SSR), and cardiorespiratory reflex tests. Mean values from alcoholic patients were significantly lower than those from control subjects for all tests. The number of secreting sweat glands (SGN) was below normal in the foot of 18 patients, and in the hand of 7 patients; 16 patients had absent SSR on the sole, and 4 on the palm. Only two patients had both test results abnormal on the hand and 10 on the foot. The SGN did not correlate with the amplitude of the SSR in the subjects studied. There was no clear correlation of abnormalities found in cardiorespiratory tests and sympathetic tests. Abnormalities in sensory nerve conduction were associated with absent SSR, but not with decreased SGN. The silicone mold technique is a more specific test to detect abnormalities in sympathetic efferent fibers, as SSR may be influenced by sensory afferent fiber involvement. © 1993 John Wiley & Sons, Inc.     

Waveform variation and size of sympathetic skin response: regional difference between the sole and palm recordings.

OBJECTIVE: The aim of this study was to investigate the regional difference in sympathetic skin response (SSR). The influence of SSR waveform from sole skin (S-SSR) on latency, amplitude, and habituation was also studied. METHODS: Twenty SSRs were analyzed in 41 normal subjects. Waveforms were classified as either the P type, in which the positive component was larger than the negative one, or the N type, in which the negative component was larger the positive one. The occurrence patterns of these two waveform types were classified into three kinds, i.e. P, N, and M patterns. In the P or N pattern all the SSRs were of the P or N type. The M pattern had both P and N types during consecutive recordings. RESULTS: In the S-SSR, the P pattern had a higher amplitude and shorter latency than the N pattern, and habituation was most pronounced in the M pattern. These were compatible with previously reported findings in SSR from palm (P-SSR). The waveform patterns were not always consistent between P- and S-SSRs. The maximum S-SSR and P-SSR were not simultaneously obtained in nearly half of the subjects. CONCLUSIONS: The size and waveforms of SSR were modified not only by the condition of the central component, but also the peripheral component of the reflex and the sweat gland.     

POSSIBLE USE OF SYMPATHETIC SKIN RESPONSE AND THERMOGRAPHY IN ASSESSING THE EFFECTS OF SYMPATHECTOMY: A CASE REPORT

The objective assessment of sympathectomy is clinically difficult. Its success is usually judged in terms of patient's improvement.
Aim: This study tested the hypothesis of possible use of Thermography and Sympathetic Skin Response (SSR) in assessing the effects of sympathectomy.
Case history: A man suffering from chronic, disabling palmar hyperhidrosis underwent a bilateral, localised, endoscopic resection of the thoracic sympathetic chain, immediately below the second thoracic ganglion. After the operation he had a significant reduction of palmar hyperhidrosis, but he did not feel satisfied with the operation due to distal paresthesias associated with thermal allodynia in the upper limbs and excessive, troublesome compensatory sweating of the trunk and lower limbs. We evaluated him fifteen months after the operation and symptoms were still present. Standard neurological examination was normal apart from a mild heat hyperesthesia in the distal portions of upper limbs.
Methods: SSR was evoked by auditory, alerting stimuli and recorded simultaneously from palm and sole bilaterally. We preferred to use auditory stimulation because of the low variability of SSR waveform usually obtained with this method. The amplitude of SSR in the palm and sole were measured and a palm/sole ratio was calculated. Total body thermography was also performed.
Results: A clear reduction in SSR palm/sole ratio was observed. Thermography showed a thoracic thermal level with the upper part of the body being warmer than the lower.
Conclusion: Judging from the results obtained in this single case, both SSR and Thermography appear to be objective, simple, noninvasive tools for assessment of thoracic simpathectomy effectiveness. Studies on a large population of patients are needed.     

Sudomotor function in autonomic failure

We measured sweat production to direct gland stimulation with intradermal methacholine in patients with autonomic failure and in normal subjects. The sympathetic skin response (SSR) to electrical stimulation was assessed in some of the same subjects. Patients with pure autonomic failure (PAF) and multiple system atrophy (MSA) produced significantly less sweat than controls. None of the patients manifested greater than normal sweat production. Impaired sweat gland function does not differentiate MSA and PAF. The SSR did not correlate with sweat response to methacholine. An SSR can occur in the absence of normal sweat gland function. The diminished production of sweat in response to intradermal methacholine in PAF suggests that human sweat glands do not develop chronic denervation supersensitivity. Intradermal methacholine is a simple method to assess sweat gland function.     

The effects of transcranial direct current stimulation on conscious perception of sensory inputs from hand palm and dorsum

Conscious perception of sensory signals depends in part on stimulus salience, relevance and topography. Letting aside differences at skin receptor level and afferent fibres, it is the CNS that makes a contextual selection of relevant sensory inputs. We hypothesized that subjective awareness (AW) of the time at which a sensory stimulus is perceived, a cortical function, may be differently modified by cortical stimulation, according to site and type of the stimulus. In 24 healthy volunteers, we examined the effects of transcranial direct current stimulation (tDCS) on the assessment of AW to heat pain or weak electrical stimuli applied to either the hand palm or dorsum. We also recorded the vertex‐evoked potentials to the same stimuli. The assessment was done before, during and after cathodal or anodal tDCS over the parietal cortex contralateral to the hand receiving the stimuli. At baseline, AW to thermal stimuli was significantly longer for palm than for dorsum (P < 0.01), while no differences between stimulation sites were observed for the electrical stimuli. Both cathodal and anodal tDCS caused a significant shortening of AW to thermal stimuli in the palm but not in the dorsum, and no effects on AW to electrical stimuli. Longer AW in the palm than in the dorsum may be attributable to differences in skin thickness. However, the selectivity of the effects of tDCS on AW to thermal stimulation of the glabrous skin reflects the specificity of CNS processing for site and type of sensory inputs.     

A study of pain threshold in diabetics with neuropathic foot lesions.

Pain thresholds to a pinch stimulus were measured at eight sites on the dorsum of both feet from 17 diabetic patients. Sixteen feet had neuropathic ulcers and seven had Charcot arthropathy. Vibration perception thresholds, radial nerve action potentials, muscle action potentials of flexor digitorum brevis, autonomic cardiovascular reflexes and reflex sweat output were also measured. Pinch pain threshold was abnormal in 15 diabetic feet, 11 having one or more insensitive sites. There was a greater variability in threshold between sites tested in diabetic than control subjects.     

Primary somatosensory cortex is actively involved in pain processing in human

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.     

Afferent pathways of sympathetic skin response in spinal cord: a clinical and electrophysiological study.

BACKGROUND: Sympathetic skin response (SSR) recording is an established test of sudomotor autonomic functions. However, knowledge of its pathways in spinal cord is putative. OBJECTIVE: This study involved subjects with isolated spinal cord lesions to evaluate the afferent pathways of SSR. METHODS: Clinical examination was done according to standard neurological classification of spinal cord injury. Electrophysiological evaluation included: (1) conventional nerve conduction studies to exclude peripheral nerve lesions, (2) scalp somato-sensory-evoked potentials (SEP) with posterior tibial nerve (PTN) stimulation and (3) SSR recording from palm by stimulating supra orbital nerve (SON) at forehead, and PTN at ankle. Subjects with absent SSR in palm to SON stimulation were excluded. In such patients, the afferent tracts were considered abnormal when SSR was absent in palm on stimulation of PTN. RESULTS: Among 37 subjects (age-28.1+/-12.8 years), the afferent tracts of SSR were affected in 13. Sparing of afferent SSR tracts correlated with preservation of bladder sensations (P<0.01). There was no correlation between SSR and SEP. CONCLUSIONS: Spinal cord lesions frequently involve afferent tracts of SSR. Spinal afferents of SSR are closely related with tracts of bladder sensations and are different from pathways for SEP.     

Sympathetic skin response evoked by respiratory stimulation as a measure of sympathetic function.

OBJECTIVES: To compare respiratory and electrical methods of evoking a sympathetic skin response (SSR). METHODS: SSRs evoked by both electrical and respiratory stimulation were recorded from the palms of 47 healthy volunteers. Expiration and inspiration were used as separate stimuli. The correlation coefficients between the amplitude and latency of the SSR from the palm electrodes and the various components of heart rate variability were calculated. RESULTS: Waveform patterns of the SSRs obtained from electrical stimulation showed varied responses to and habituation to this type of stimulation. On the other hand, no subjects showed a phase change in SSR waveform patterns between the first and last expiratory stimuli. The potentials recorded after expiratory stimulation had significantly greater amplitudes than those recorded after electrical stimuli. The low frequency component of heart rate variability induced by expiratory stimulation was significantly greater than that induced by electrical stimulation. The SSR may also correlate strongly with the change of respiratory rate since a more rapid pressure change occurs during expiratory movement than during inspiratory movements. CONCLUSIONS: The SSR evoked by expiratory stimulation is more reliable than either electrical stimulation or inspiratory stimulation for determining sympathetic function.     

QUANTITATIVE SENSORY TESTING AND SWEAT FUNCTION IN FRIEDREICH''S ATAXIA. CORRELATION WITH CUTANEOUS INNERVATION

To evaluate small fiber function in Friedreich's Ataxia (FA), we performed in 7 patients pin-prick, thermal thresholds, and sweat test. All tests were performed in four different sites: hand dorsum, anterior thigh, lateral distal leg, and foot dorsum. The same subjects underwent 3 mm punch skin biopsy from fingertip, anterior thigh, and lateral distal leg. We used a thin needle mounted on a calibrated nylon wire for the pin-prick test, and a Medoc 2001 TSA system for thermal threshold assessment. Sweat test was performed using a silicon mold after stimulation with pilocarpine by iontophoresis.
Skin specimens, cut into 100-μm-thick sections, were double-stained using primary antibodies specific for collagen and nervous fibers and secondary antibodies labeled with Cy3 and Cy5 fluorophores. Tridimensional digitized images were obtained from z-series of 2-μm-thick optical sections acquired with a confocal microscope.
We found in all patients in the more distal sites definite signs of functional impairment of the small fibers. These data correlated with the skin innervation morphological findings that showed, in the same sites, a sensible loss of small fibers regarding both the epidermal free endings and the subepidermal neural plexus. Less severe morphological abnormalities were found in the proximal sites.
The large fiber neuropathy in FA is well documented. Our data show a length-dependent involvement of small fibers in the pathological process.     

Enhanced magnetic auditory steady-state response in early Alzheimer's disease.

OBJECTIVE: Previous studies have reported abnormalities in both spontaneous and evoked electromagnetic brain activity in Alzheimer's disease (AD). We studied the auditory steady-state response (SSR) which represents the net effect of entrained background activity and superimposed cortical evoked responses, in AD patients and healthy controls. METHODS: Whole-head magnetoencephalography (MEG) was used to measure SSR to monaural 40-Hz stimulation in AD patients and age-matched controls. Equivalent current dipoles (ECD) of the SSR were modeled in each hemisphere, and source amplitudes were compared between the two groups using time-varying ECD models. RESULTS: Our results indicate that the SSR is significantly increased in AD patients with mild to moderate cognitive deterioration in comparison with healthy elderly subjects. CONCLUSIONS: Goal-directed functioning requires optimization of inhibitory and excitatory inputs in the cortex, allowing the adaptation of responsiveness to repetitive stimulation with low relevance. The present results suggest that this balance is impaired in AD, manifesting itself in decreased inhibition in cortical auditory processing and impaired adaptation of the stimulus-locked activity, probably due to abnormalities in cholinergic modulation. SIGNIFICANCE: MEG appears to be a sensitive tool to detect abnormalities of auditory processing already in early stages of AD.     

Sympathetic skin response. Glabella stimulation may be more useful than peripheral nerve stimulation in clinical practice

The aim is to verify whether glabella electrical stimulation evokes sympathetic skin responses (SSR) without inter-side differences in latency and area of the responses and is more useful in mononeuropathies than peripheral nerve stimulation. SSRs were recorded in 25 healthy subjects from right palm, third (M3SSR) and fifth fingers and contralateral third finger. The inter-side differences of grand mean area and mean of largest area of M3SSR were significant only by ulnar nerve and not by glabella stimulation. Therefore glabella stimulation may be used in mononeuropathies comparing SSR area recorded from affected side with respect to contralateral healthy side.     

Sympathetic skin response in incomplete spinal cord injury with urinary incontinence

Objectives:

Sympathetic skin response (SSR) is a test for evaluation of the sympathetic sweat gland pathways, and it has been used to study the central sympathetic pathways in spinal cord injury (SCI). This study aimed to assess the autonomic pathways according to normal or abnormal SSR in urinary incontinence patients due to incomplete spinal cord injury.

Materials and Methods:

Suprapubic, palmar, and plantar SSR to the peripheral nerve electrical stimulation were recorded in 16 urinary incontinence patients with incomplete spinal cord injury at various neurological levels and in 30 healthy control subjects.

Results:

All the recordings of SSR from the incomplete SCI patients with urinary incontinence as compared with their counterparts in the control group showed significantly reduced amplitudes with more prominent reduction in the suprapubic area recording site (P value < 0.0004). SSR with significantly prolonged latencies were recorded from palm and plantar areas in response to suprapubic area and tibial N stimuli, respectively (P value < 0.02). In this study, a significantly higher stimulus intensity (P value < 0.01) was needed to elicit SSR in the cases compared with the control group.

Conclusion:

This study showed abnormal SSR in urinary incontinence patients due to incomplete SCI. In addition, for the first time we have described recording of abnormal SSR from the suprapubic area as another way to show bladder sympathetic system involvement.     

Unmasking of an early laser evoked potential by a point localization task.

OBJECTIVES: The investigation of the CO(2) laser evoked potential (LEP) modifications following a point localization task. METHODS: LEPs were recorded from 10 healthy subjects in two different conditions. (1) Task condition: laser stimuli were shifted among 3 different locations on the right hand dorsum, and the subjects were asked to identify the stimulated area. The mean error rate in point localization was 4.5%. (2) Non-task condition: laser pulses were delivered on the first intermetacarpal space, and the subject was asked to count the number of stimuli. The mean error rate in counting was 5.8%. RESULTS: In the task condition, the temporal traces contralateral to the stimulation showed an early positive component (eP, mean peak latency 83 ms) preceding the N1 negativity (mean peak latency 144 ms). At the eP peak latency, topographic maps showed a positivity highly focused on the contralateral temporal region. In the non-task recordings no reliable response was identifiable before the N1 potential. CONCLUSIONS: While no LEP component earlier than the middle-latency N1 potential can be recorded in the non-task condition, a positive response (eP) preceding the N1 component is identifiable in the contralateral temporal region during the spatial localization of painful stimuli. The eP scalp distribution is compatible with its origin from a radial source in the second somatosensory (or insular) area, thus suggesting that the opercular cortex is involved not only in the middle-latency (N1 potential), but also in early pain processing.