Sympathetic skin response (SSR) is abnormal in multiple sclerosis

As the function of the autonomic nervous system is often compromised in multiple sclerosis (MS), different standardized tests are used to detect disseminated abnormalities in cardiovascular autonomic functions. Sympathetic skin response (SSR), a slow wave generated in deep layers of the skin, is induced by reflex activation of sudomotor sympathetic efferent fibers. SSR was studied in 70 patients classified into different categories according to the diagnostic criteria for MS. We also obtained pattern reversal visually evoked potentials and brainstem auditory evoked potentials as well as somatosensory evoked potentials (by median and posterior tibial nerve stimulation). SSR was abnormal in 66 patients (94.2%), including abnormal foot latency with normal hand latency in 30 (42.8%), delayed foot and hand latencies in 30 (42.8%), and no response in 6 (8.6%). The percentages of SSR abnormalities were similar in the different patient categories. Pathological SSR were more common than abnormal evoked potentials in suspected and probable MS. SSR appears to be a simple and effective means of assessing sympathetic sudomotor outflow disturbances in MS, providing a valuable addition to current electrophysiological procedures for the detection of MS lesions.© 1995 John Wiley &Sons, Inc.     

Sympathetic skin response in hemispheric lesions.

We recorded the sympathetic skin response (SSR) from electrical nerve stimulation in 16 patients with cerebrovascular accident (CVA). Location and nature of the lesion were documented by computerized tomography (CT). Median (pre-rolandic and parietal) somatosensory evoked potentials (SEP) were also recorded. SSR was absent bilaterally in eight hemiplegics after stimulation of the plegic side and present bilaterally after stimulation of the normal side in the first weeks after CVA. Parietal and pre-rolandic SEPs were absent in the affected hemispheres. SSR was present bilaterally after stimulation of each side in the remaining CVA cases with reduced amplitude SEPs. Absence of the electrically evoked SSR in hemispheric lesions may be due to involvement of central afferent pathways or temporary suppression of suprasegmental excitatory influences.     

Sympathetic skin response in psoriasis and vitiligo.

The sympathetic skin response (SSR) which is considered to be one of the indexes of peripheral autonomic nerve function, especially evaluates sudomotor function of unmyelinated sympathetic fibers. This noninvasive technique has been studied in various neurological disorders particularly in peripheral neuropathies and also in some dermatological disorders associated with nervous system involvement. However, literature lacks sufficient data regarding SSR in immunologically mediated skin disorders. We enrolled patients with vitiligo and psoriasis to determine the possible effects of these disorders on SSR. Examination of SSR was performed in 30 patients with psoriasis and 15 patients with vitiligo as well as in 23 healthy volunteers as controls. Right and left median nerves were stimulated successively and responses were recorded from the palms simultaneously. SSR could be obtained from every subject. The groups were not statistically different for the values of the latency, the amplitude, and the area under the negative component of SSR. Our results indicated that vitiligo and psoriasis did not have any significant effects on SSR.     

Sympathetic skin response in carpal tunnel syndrome.

OBJECTIVES: Sudomotor efferent nerve fiber function was studied in carpal tunnel syndrome (CTS). METHODS: Bilateral median and ulnar sympathetic skin response (SSR) were recorded by sternal stimulation in 22 bilateral and 9 unilateral patients and compared with 21 healthy volunteers. RESULTS: There was no significant difference between median and ulnar nerve SSR latency, amplitude or area. The median nerve SSR was not different from that of the controls. The median-to-ulnar ratios of SSR parameters were not different in patients and controls. However, the median-to-ulnar ratios of SSR amplitude and area were lower than normal in 3 out of 7 patients with normal nerve conduction whereas this abnormality was found in only 4 out of 46 patients with abnormal nerve conduction. CONCLUSIONS: Normal SSR results, even in patients with complaints related to sudomotor sympathetic dysfunction, indicate that the SSR does not seem to be a sensitive diagnostic method in CTS.     

Sympathetic skin response asymmetry in early stage idiopathic Parkinson's disease.

Simultaneous bilateral plantar sympathetic skin response (SSR) was studied in 25 patients with early stage idiopathic Parkinson's disease (IPD), characterized by monolateral motor involvement (Hoehn and Yahr, stage <2) and without clinical evidence of autonomic dysfunctions. Thirteen (mean age: 68.69 +/- 7.70, range 55-76) had extrapyramidal clinical signs only at the left body side, 12 (mean age 66.60 +/- 7.43, range 51-73) at the right body side. A group of 25 healthy, age-matched, subjects were also evaluated. To evoke the responses, trains of 10 electrical pulses were applied at different intensities and frequencies. Only intensities of stimulation > or = 5 times the sensory electrical threshold always assured bilateral plantar responses in all the examined subjects. Amplitude asymmetry between left and right responses was found only in the IPD patients (P < 0.05). The amplitude reduction corresponded to the motor affected side. No analogue latency variation was observed in any group. Independently from the peripheral or central origins of such phenomena, these findings suggest that simultaneous bilateral SSR amplitude evaluation could be useful, in early IPD patients, to demonstrate and to monitor the sympathetic cholinergic dysfunction, despite the lack of autonomic symptoms.     

Sympathetic skin response: normal results in different experimental conditions.

(1) The sympathetic skin response (SSR) is a slow wave, generated in deep layers of the skin, resulting from reflex activation of the sudomotor sympathetic efferent fibres. The aim of this study was to define experimental conditions, best stimulation and recording procedures, and the criteria for validation of the responses. (2) Thirty normal subjects (aged 25-56) were tested. The stimulation was an electrical pulse train applied to the median nerve at the wrist, a binaural tone burst, or both simultaneously. Records were made with surface electrodes on hand and foot contralateral to the stimulated median nerve. (3) Response shape was most often biphasic in feet, biphasic or triphasic in hands. SSR amplitude was 3.1 +/- 1.8 mV in hands, 1.4 +/- 0.8 mV in feet. Normal mean onset latency was 1.5 +/- 0.08 sec for hand response, 2.05 +/- 0.10 sec for foot response. The mean conduction velocity along peripheral sympathetic nerve fibres was 1.40 +/- 0.14 m/sec in lower limbs. (4) Bimodal stimulation (burst + median) provided responses of larger amplitude. The influence of stimulation intensity was also investigated. A decrease in amplitude and lengthening of latencies were observed after 15-20 min of testing. (5) The criteria for validation of responses are discussed. The importance of central processing time in the response delay is pointed out. In good methodological conditions, SSR would appear to be a simple, effective means of assessing sympathetic sudomotor outflow in central and peripheral nervous system disorders.     

Sympathetic skin response in patients with peripheral arterial occlusive disease.

OBJECTIVE: The current study aimed to assess the viability of sympathetic sudomotor fibers in patients suffering from mild peripheral arterial occlusive disease (PAD). METHODS: Sympathetic skin response (SSR) from the hand (electrical stimulation) and sole (electrical and magnetic stimulation) of 25 patients with PAD (19 males and 6 females with mean age 62.7 +/- 10.2 years) was recorded unilaterally depending on the side of the affected limb (18 right side, 7 left side). Electrophysiological data were also collected and correlated with the SSR results. Twenty-five, age- and gender-matched healthy volunteers served as controls. RESULTS: No evidence of nerve conduction abnormalities was recorded from the group of patients. Intact SSR recordings were obtained from the upper limb of patients. Nine patients (36%) had absent SSR in the lower limb following electrical stimulation, whilst the same 9 patients had absent SSR following magnetic stimulation. Significant differences occurred between groups in the SSR latency scores recorded from the lower limb. Following electrical stimulation the mean SSR latency in patients was significantly prolonged, compared to that of controls (P = 0.000), whilst the same applied following magnetic stimulation (P = 0.000). There was no correlation between SSR abnormalities and nerve conduction measurements. The manifestation of intermittent claudication at a walking distance of 250 m was strongly correlated with absent lower limb SSR (r = 0.71, P = 0.035). CONCLUSIONS: SSR abnormalities appeared to be an early and independent finding of neural impairment in our patients. SIGNIFICANCE: SSR study, performed at an early stage of PAD may prove useful in differentiating PAD-induced neuropathy from other neuropathic processes.     

Sympathetic skin response and axon count in carpal tunnel syndrome.

The aim of this study was to determine the sensitivity of sympathetic skin response (SSR) in evaluating autonomic involvement in carpal tunnel syndrome (CTS) while simultaneously showing the axonal loss by motor unit number estimation (MUNE). Bilateral SSR were recorded by suprasternal stimulus in 50 hands of 31 patients and compared with 50 hands of 25 healthy volunteers. The groups were examined for sympathetic symptoms and sympathetic symptom scores (SSS) were determined. Axon count was performed on the abductor pollicis brevis (APB) muscle by using the MUNE method (with incremental technique) in both groups. There was no SSR difference between groups, although a significant difference was found for SSS. No relationships were found between SSR parameters and SSS or the electrophysiologic stage. MUNE of the APB muscle was significantly lower in CTS group and there was a negative correlation between MUNE and the electrophysiologic stage. The comparison of the MUNE and the amplitude of median compound muscle action potential indicated that MUNE is a highly sensitive method of determining severity in patients with CTS. In evaluating autonomic involvement in CTS, SSR does not seem to be a sensitive method. MUNE is a good indicator of motor reserve and can be helpful when following the treatment and prognosis of CTS in clinical practice.     

Sympathetic skin response differentiates hereditary sensory autonomic neuropathies III and IV.

OBJECTIVE: To evaluate whether sympathetic skin response (SSR) differs in patients with hereditary sensory autonomic neuropathy (HSAN) types III and IV. BACKGROUND: HSAN types III and IV are rare autosomal recessive disorders that cause many similar autonomic, sensory, and motor dysfunctions, but different sweating characteristics. HSAN III patients have preserved and at times, excessive sweating, whereas anhidrosis is characteristic of HSAN IV. SSR reflects the integrity of sympathetic sudomotor fibers and the activation of sweat glands through the change in skin resistance in response to an arousal stimulus. Therefore, SSR is a test method that might facilitate differential diagnosis of HSAN III and IV. METHODS: In 17 HSAN III patients (eight women, nine men; mean age, 20.65+/-5.45 years) and seven HSAN IV patients (five girls, two boys; mean age, 10.0+/-5.45 years) SSR was recorded from the palms and soles after repeated electrical, acoustic, and inspiratory gasp stimulations. In addition, all subjects underwent a neurologic examination; studies of median, peroneal motor, and sural nerve conduction velocities; and determination of vibratory and thermal perception thresholds. RESULTS: Although clinical differences were appreciated between the two types of HSANs, both HSANs had evidence of small-fiber involvement. Both HSANs had abnormal temperature and pain perception. In contrast, SSR was preserved in all HSAN III and absent in all HSAN IV patients. CONCLUSION: SSR provides another parameter to improve differentiation of HSAN III from HSAN IV, and also gives us additional information regarding sympathetic sudomotor fiber function in these developmental diseases.     

Sympathetic skin responses from postauricular region in Meniere's disease.

OBJECTIVE: To investigate the sympathetic nervous system activity in Meniere's disease (MD) by recording sympathetic skin responses (SSRs) from the postauricular region (PA). METHODS: Twenty-one patients with definite unilateral MD diagnosis and 12 healthy volunteers were studied by evoking right and left PA-SSRs with electrical stimulation of the left median nerve at the wrist in attack and interval periods of MD. Mean latencies and maximum amplitudes were used in statistical analyses. RESULTS: In unilateral definite MD patients, the mean latencies were longer and the maximum amplitudes were smaller on the involved ear side than those on the normal ear side (p<0.01 for both amplitude and latency) and than those from the controls (p<0.01 and p<0.05). In three patients, there was no detectable PA-SSR on the involved ear side while there were SSRs on the healthy side. In four patients, the responses were absent bilaterally during the attack period. CONCLUSIONS: There is a marked asymmetric sympathetic hypofunction in the area of the PA region of the involved ear in MD patients. SIGNIFICANCE: The PA region is a new site for recording sympathetic skin responses. PA-SSR is a useful tool to investigate sympathetic nervous system function in MD patients.     

Sympathetic skin response and heart rate variability in patients with Huntington disease.

OBJECTIVE: To examine the autonomic nervous system functions in patients with Huntington disease. BACKGROUND: Although patients with Huntington disease frequently experience vegetative symptoms, it is not clear if there is dysfunction of the autonomic nervous system. METHODS: Sympathetic skin response (SSR) latency and amplitude from both palms and soles and R-R (heart rate) interval variation (RRIV) at rest and during the Valsalva maneuver were examined in 22 patients and 21 age-matched controls. Unified Huntington's Disease Rating Scale scores were determined in all the patients. RESULTS: Our data are reported as means +/- SEMs. The SSR latencies in patients (mean palm latency, 1835.8+/-110.7 milliseconds; mean sole latency, 2625.3+/-226.9 milliseconds) were prolonged compared with controls (mean palm latency, 1359.5+/-28 milliseconds [P<.01]); mean sole latency, 2038.1+/-44.9 milliseconds [P<.01]) and amplitudes in patients (mean amplitude, 1063.1+/-237.7 microV) were smaller compared with controls (mean amplitude, 1846.3+/-251.2 microV [P<.05]). The RRIV in patients both at rest (mean RRIV in patients, 3.7%+/-0.4% vs. controls, 9.7%+/-0.6% [P<.01]) and during the Valsalva maneuver (mean RRIV in patients, 6.3%+/-1.6% vs. controls, 14.5%+/-1.2% [P<.01]) was lower compared with controls. Furthermore, the prolonged SSR latencies, smaller amplitudes, and lower RRIV in patients compared with controls closely correlated with the various components of the Unified Huntington's Disease Rating Scale scores (total behavior score and SSR latency, R = 0.6 [P<.01]; total behavior score and SSR amplitude, R = -0.5 [P<.05]; total behavior score and RRIV, R = -0.4 [P<.05]; verbal fluency and SSR latency, R = -0.5 [P<.05]; verbal fluency and SSR amplitude, R = 0.5 [P<.05], verbal fluency and RRIV, R = 0.5 [P<.05]; total functional capacity and SSR latency, R = -0.6 [P<.01]; total functional capacity and SSR amplitude, R = 0.5 [P<.05]). CONCLUSION: These results suggest that there is autonomic nervous system dysfunction in patients with Huntington disease.     

Sympathetic skin responses of the hand in normal subjects: shorter latency at distal phalanx

We studied the conduction of the sympathetic skin response (SSR) in the hands of 35 normal subjects by simultaneous recording at five sites. The mean latency of the SSR in all subjects increased from the wrist (W) to the middle phalanx (M), but the SSR latency at the distal phalanx (D) was shorter than that at the middle phalanx. The mean conduction time and conduction velocity from W to M was 197.5 ms and 0.87 m/s, respectively, and that from W to D was 48.8 ms and 2.34 m/s, respectively. For evaluation of the cause of the shorter latency at D, digital nerve blocking was performed in two subjects. The blocking of the volar digital nerves at the proximal phalanx abolished SSR at M and D. It was postulated that the initiation or conduction of sudomotor nerve impulse to the distal phalanx would be facilitated compared with those to the other proximal sites in the hand. The SSR conduction time between W and M may be a means of detecting alteration of sympathetic sudomotor nerve activity.     

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.     

Sympathetic skin response as an objective tool to estimate stimulus-associated arousal in a human model of hyperalgesia

BackgroundPain is a private experience, whose assessment relies on subjective self-reporting. Inaccurate communication renders pain evaluation unreliable in individuals with alteration of consciousness, lack of verbal interaction, cognitive dysfunction or simple malingering, hence the importance of developing reliable objective assessment tools.ObjectivesSince pain is associated with autonomic arousal, here we used readouts of autonomic activity to assess objectively the arousing effect of somatic stimuli in a human model of hyperalgesia.MethodsWe used topical capsaicin to induce cutaneous hypersensitivity in the right arm of 20 healthy volunteers, and recorded sympathetic skin responses (SSR) and numerical perceptive ratings (NRS) to stimulation of the sensitized region and its homologous contralateral site, using brush (Aβ), pinprick (Aδ) and laser (C-Warmth) stimuli.ResultsBoth subjective ratings and SSRs were significantly enhanced to stimulation of the sensitized region, and their respective ratios of maximal enhancement were positively correlated. At individual level, a significant association was observed between SSR and NRS behavior (χ2(1)= 11.03; p < 0.001), with a positive predictive value of 87% (CI95 [77-97%]) for SSR increase predicting enhancement of subjective reports. A “lie experiment” asking subjects to simulate elevated NRS failed to enhance SSRs. Significant habituation of SSRs appeared when stimuli were repeated at ～15s intervals, hence decreasing their negative predictive value when several consecutive stimuli were averaged (NPV=46%; CI95 [30-62%]).ConclusionThe SSR may represent a rapid and reliable procedure to assess cutaneous hypersensitivity, simple to use in clinical practice and resistant to simulation. Rapid habituation is a drawback that can be countered by using few repetitions and low stimulus rates.     

Central projections from the skin of the hand in squirrel monkeys.

Central termination patterns of afferents from the hands of squirrel monkeys were studied after subdermal injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) or cholera toxin subunit B conjugated to HRP (BHRP). WGA-HRP more effectively labeled axons terminating in the superficial dorsal horn of the spinal cord, while BHRP more effectively labeled axons terminating in the deeper layers. Injections of both tracers, when restricted to parts of glabrous digits, palm, or dorsal hand, revealed somatotopic patterns in the spinal cord and pars rotunda of the cuneate nucleus that were, in some respects, similar and, in other respects, quite different from those previously reported for macaque monkey (Florence et al., J. Comp. Neurol. 286:48-70, '89). As in macaques, injections in digits 1-5 produced a rostrocaudal sequence of foci of terminations in the cervical spinal cord. However, inputs from the palm were located medial to those from the digits, whereas the palm is represented lateral to the digits in macaque monkeys. Since inputs from the palm is also medial in the dorsal horn in cats (Nyberg and Blomqvist, J. Comp. Neurol. 242:28-39, '85), the condition in squirrel monkeys may be similar to the generalized state. In the cuneate nucleus, single injections in the hand produced dense label in the pars rotunda, and sparse label in the rostral and caudal poles. As in macaque monkeys, inputs from specific parts of the hand related to rostrocaudal clusters of cells that are cytochrome oxidase dense. The representation of the digits differed from macaques in that the digits were represented dorsal to the palm, rather that ventral to the palm as in macaques. Again, comparisons with cats suggest that squirrel monkeys have the more generalized pattern. Finally, inputs from the hair, dorsal surfaces of the digits terminated on the same clusters as the inputs from the glabrous, ventral surfaces, apparently overlapping somewhat. The proximity of these terminations from dorsal and ventral surfaces of the digits may be related to observations that cortical representations of the glabrous surfaces of digits become responsive to dorsal surfaces of the same digits when inputs from glabrous skin are chronically deactivated (e.g., Merzenich et al., Neuroscience 3:33-55, '83).