Quantitative Sudomotor Axon Reflex Test Research Articles

Autonomic dysfunction is frequent and disabling in non-paraneoplastic sensory neuronopathies

IntroductionSensory neuronopathies (SN) are characterized by asymmetric non-length dependent sensory deficits and sensory ataxia. Autonomic dysfunction in SN was not yet evaluated regarding its frequency, characteristics and relationship to sensory deficits. To address these issues, we performed a comprehensive clinical and neurophysiological evaluation of a large cohort of patients with non-paraneoplastic SN (np-SN). MethodsWe enrolled 50 consecutive patients with npSN and 32 age/sex-matched healthy controls. They were clinically evaluated (SCOPA-Aut scale) and underwent neurophysiological autonomic assessment (quantitative sudomotor axon reflex test, heart rate variability and sympathetic skin response). ResultsMean age of patients was 50.9 ± 10.3 years and there were 18 men. npSN patients had higher SCOPA-Aut scores than controls (26.63 ± 12.72 vs. 12.66 ± 9.11, p < .001). QSART was abnormal in 92% of the patients - sweat volumes in all examined sites were smaller among patients (p < .001). Cardiovascular autonomic neuropathy was more frequent in these patients as well (p < .001). ConclusionAltogether our results suggest that autonomic dysfunction in distinct domains is frequent in npSN patients. These findings suggest that the clinical picture of npSN is related to a double neuronopathy: sensory and autonomic.

Autonomic dysfunction in hereditary spastic paraplegia type 4.

SPAST mutations are the most common cause of hereditary spastic paraplegia (SPG4-HSP), which is characterized by progressive lower limb weakness, spasticity and hyperreflexia. There are few studies about non-motor manifestations in this disease and none about autonomic involvement. Therefore, the aim was todetermine the frequency and pattern of autonomic complaints in patients with SPG4-HSP, as well as to determine the clinical relevance and the possible factors associated with these manifestations. Thirty-four molecularly confirmed SPG4 patients were recruited in a multicenter cross-sectional study, of whom 26 underwent detailed neurophysiological testing (heart rate variability, sympathetic skin response and the Quantitative Sudomotor Axonal Reflex Test). The Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire (SCOPA-AUT) was applied to quantify the severity of autonomic symptoms. Results were compared with 44 age- and gender-matched healthy controls using non-parametric tests. P values <0.05 were considered significant. In the SPG4-HSP group, there were 18 men with a mean age of 47.7±12.6years. SCOPA-AUT scores were similar between patients and controls (P=0.238). Only the urinary domain subscore was significantly higher amongst patients (4 vs. 2.5, P=0.05).Absent sympathetic skin response in the hands and feet was more frequent amongst patients (20% vs. 0%, P<0.001, and 64% vs. 0%, P=0.006, respectively). Quantitative Sudomotor Axonal Reflex Test responses were also smaller throughout all recording regions in the SPG4-HSP group. Our results indicate that SPG4-HSP patients have sudomotor dysfunction caused by damaged small post-ganglionic cholinergic fibers. Damage in SPG4-HSP extends to the peripheral nervous system.

'Sirim' (Cold) Pain as a Common Symptom in Korean Patients with Clinically Suspected Small-Fiber Neuropathy.

Background and PurposeDiagnosing small-fiber neuropathy (SFN) is challenging because there is no gold-standard test and few diagnostic tests. This study investigated the clinical symptom profile and its associations with the results of quantitative sensory testing (QST) and the quantitative sudomotor axon reflex test (QSART) as well as the quality of life (QOL) in patients with clinically suspected SFN.MethodsThis study involved 63 patients with clinically suspected length-dependent SFN. Assessments were performed using QST, QSART, SFN Symptoms Inventory Questionnaire, Neuropathic Pain Symptom Inventory, ‘Sirim’ frequency and ‘Sirim’ (cold) pain severity, and 36-item Short-Form Health Survey. Multiple logistic and linear regression analyses were performed to predict risk factors for QST or QSART abnormalities and QOL, respectively.Results‘Sirim’ and ‘Sirim’ pain was the most-common (84%) and the most-severe complaint (mean score of 6.3 on a numerical rating scale ranging from 0 to 10) in patients with clinically suspected SFN. The findings of QST [cold detection threshold (CDT)] and QSART were abnormal in 71% (n=45/57) and 62% (n=39/56) of the patients, respectively. An abnormal CDT was correlated with more-severe stabbing pain (odds ratio=2.23, 95% CI=1.02–4.87, p=0.045). Restless-leg symptoms (β=−7.077) and pressure-evoked pain (β=−5.034) were independent predictors of the physical aspects of QOL.Conclusions‘Sirim’ pain, similar to cold pain, should be considered a major neuropathic pain in SFN. Among pain characteristics, stabbing pain of a spontaneous paroxysmal nature may be more pronounced in the setting of dysfunctional Aδ fibers with functional autonomic C fibers.

Chapter 27 - Pure autonomic failure

In this chapter, we describe the history, presentation, diagnosis and treatment of pure autonomic failure (PAF). The pathology underlying this condition is thought to involve the deposition of alpha synuclein in the autonomic ganglia leading to diminished norepinephrine release and progressive autonomic dysfunction. We focus on various neurophysiological tests that may be used to evaluate the function of the peripheral autonomic nervous system including quantitative sudomotor axon reflex testing, thermoregulatory sweat testing, and others. These may help evaluate and diagnose various disorders of autonomic failure and neurogenic orthostatic hypotension including multiple system atrophy and Parkinson's disease dysautonomia. Management of PAF, including the therapeutic role of recent advances in pharmacologic treatment, is discussed.

An updated normative data set from the autonomic reflex screen representative of Southwestern Ontario.

In evaluating autonomic dysfunction, the autonomic reflex screen (ARS) is an established set of standardized tests to evaluate the presence and severity of autonomic dysfunction. Our laboratory previously reported normative data on 121 healthy individuals; however, the sample size in older individuals was reduced compared with other age groups. Therefore, the objective of the current study was to provide updated normative values representative of young, middle-aged, and older individuals from Southwestern Ontario. Two hundred and fifty-two healthy individuals completed quantitative sudomotor axon reflex testing, heart rate responses to deep breathing (HRDB), and Valsalva maneuver using standard protocols of the ARS. All 4 sweat sites demonstrated a significant effect of sex (p < 0.001). In addition, the proximal leg, distal leg, and foot were all significantly affected by age (p < 0.001). Cardiovagal parameters, measured via HRDB and Valsalva ratio revealed a significant regression with age (p < 0.001). These results show similar trends with previously reported normative data sets. All normative data as a function of age and sex, where appropriate, are expressed as percentiles (2.5th, 5th, 95th, 97.5th). The current study provides updated normative data describing autonomic functioning in healthy individuals obtained from the sudomotor and cardiovagal components of the ARS.

Sudomotor Testing of Diabetes Polyneuropathy

Objective: The performance of the Sudoscan technology for diagnosing diabetic polyneuropathy (DPN) was evaluated against the quantitative sudomotor axon reflex test (QSART). Furthermore, the association of Sudoscan with two clinical neuropathy scoring systems was evaluated.Methods: Forty-seven patients with type 2 diabetes (20 without DPN, 27 with DPN) and 16 matched controls were examined for neuropathic symptoms and for the extent of sensory deficits. Sweat latency and volume by QSART and the skin electrochemical conductance (ESC) by Sudoscan were measured.Results: The feet and hand ESC was significantly lower in patients with DPN as compared to controls. Patients with DPN had also lower hand ESC than patients without DPN. Sensitivity and specificity of feet and hand ESC for detecting DPN were 70/85% and 53/50% respectively. QSART could not differentiate between the three groups. ESC was inversely related to neuropathic symptoms and sensory impairment. ESC was significantly correlated with sensory impairment and pain.Conclusions: Sudoscan shows a good performance in detecting subjects with DPN and it correlates well with clinical signs and symptoms of neuropathy.Significance: This study provides evidence that Sudoscan has high potential to be used as screening tool for DPN and possibly also for small fiber neuropathy in diabetic patients.HIGHLIGHTS - The sudomotor function test Sudoscan shows a good performance to detect diabetes peripheral neuropathy.- Sudoscan measures significantly correlate with clinical signs and symptoms of neuropathy.- The Sudoscan technology may help to secure clinical diagnosis of small fiber neuropathy.

Autonomic symptom burden is an independent contributor to multiple sclerosis related fatigue.

To investigate a possible association between autonomic dysfunction and fatigue in people with multiple sclerosis. In 70 people with multiple sclerosis early in the disease course (51 females, mean age 33.8±9.1), quantitative sudomotor axon reflex tests, cardiovascular reflex tests (heart rate and blood pressure responses to the Valsalva maneuver and heart rate response to deep breathing), and the tilt table test were performed. Participants completed the Composite Autonomic Symptom Score 31, the Modified Fatigue Impact Scale, and the Epworth Sleepiness Scale, as well as the Beck Depression Inventory. Cutoff scores of ≥ 38 or ≥ 45 on the Modified Fatigue Impact Scale were used to stratify patients into a fatigued subgroup (N = 17 or N = 9, respectively). We found clear associations between fatigue and scores in subjective tests of the autonomic nervous system: fatigued patients scored significantly worse on Composite Autonomic Symptom Score 31, and there was a strong correlation between the Modified Fatigue Impact Scale and the Composite Autonomic Symptom Score 31 (rs = 0.607, p < 0.001). On the other hand, we found only modest associations between fatigue and scores in objective tests of the autonomic nervous system: there was a clear trend for lower sweating outputs at all measured sites, which reached statistical significance for the distal leg and foot. We found weak correlations between the Modified Fatigue Impact Scale and the Valsalva ratio (rs = - 0.306, p = 0.011), as well as between the Modified Fatigue Impact Scale and quantitative sudomotor axon reflex tests of the forearm, proximal, and distal lower leg (rs = - 0.379, p = 0.003; rs = - 0.356, p = 0.005; and rs = - 0.345, p = 0.006, respectively). A multiple regression model showed that the Composite Autonomic Symptom Score 31, Beck Depression Inventory, and Epworth Sleepiness Scale were independent predictors of fatigue (p = 0.005, p = 0.019, and p = 0.010, respectively). These results suggest that-even early in the course of the disease-people with multiple sclerosis suffer from objective and subjective impairments of the autonomic nervous system. The results also point to an association between autonomic nervous system impairment and multiple sclerosis related fatigue.

How to explore automic dysfunction on clinical practice?

Objectives Various validated clinical scales and questionnaires are available and many neurophysiological and functional tests have been developed to evaluate dysautonomia. This work aims to review the neurophysiological tools that can be used to characterize distal autonomic dysfunction, particularly in the context of peripheral neuropathies. Methods Neurophysiological tests exploring autonomic vasomotor and sudomotor function have been reviewed. The accuracy of each technique for the diagnosis of small-fiber autonomic neuropathy has been assessed. Results Sudomotor innervation can be investigated by many tests including sympathetic skin reflex recording (SSR), quantitative sudomotor axon reflex testing (QSART), electrochemical skin conductance measurement (ESC) by Sudoscan®, and the Neuropad® colorimetric test. Both the Neuropad® test and ESC measurement by Sudoscan®, provide early markers of neuropathy in context of familial amyloid polyneuropathy as well as in diabetic polyneuropathy. The Neuropad® test could be used as a screening tool, requiring confirmation by ESC measurement by Sudoscan®, which is more convenient for follow-up assessment. Unlike the SSR, QSART is also a sensitive test for detecting sudomotor dysfunction. However, its test-retest reliability is really moderate. For vasomotor aspects, investigation includes the stimulated skin wrinkling (SSW) test, laser Doppler flowmetry (LDF) and laser Doppler imaging (LDI-flare). The SSW test appears valuable when applied to the fingers, but not to the toes. The LDF and LDI-flare tests were found to be sensitive in various clinical contexts (e.g., Parkinson's disease, diabetes, and HIV infection), but they lack standardization and have poor test-retest reliability, especially LDF. Conclusion Sudomotor tests and notably ESC measurement by Sudoscan® appear to be relevant to assess distal autonomic dysfunction in the context of peripheral neuropathy, while the reliability of vasomotor tests should still be improved. Finally, various autonomic tests that are not performed at limb extremities can also be very informative and sensitive in this clinical context, such as heart rate variability measurement at deep breathing.

Correlation between sudomotor dysfunction and functional status in patients with amyotrophic lateral sclerosis

Sudomotor dysfunction is known to be common in patients with amyotrophic lateral sclerosis (ALS). Q-Sweat (Quantitative Sweat Measurement System; WR Medical Electronics Co., Stillwater, Minnesota) is modeled on quantitative sudomotor axon reflex test, which is estimated by the latency to the start of sweat secretion and the amount of sweat. The aim of this study is to find correlation between sudomotor dysfunction and functional status in patients with ALS. Medical records of 17 patients with ALS were reviewed. Functional status of subjects was scored using ALS functional rating scale (ALS-FRS). Volume of sweat at 4 different points of body (i.e. both forearms and thighs) was detected at Q-Sweat. We obtained mean value of volume measured in both upper and lower limbs, respectively, and subtracted the age-adjusted normal lower limit from those values. The difference value was called ‘SCORE’ of upper limbs and lower limbs each. In case that the SCORE measured in a patient was in normal range, it was recorded as 0 point, what means normal response of diaphoresis. Age, gender and duration from onset to the time of the test were not statistically associated with degree of sudomotor dysfunction. Negative linear correlation between ALS-FRS and SCOREs of upper ( r = −0.485, P = 0.049) and lower limbs ( r = −0.509, P = 0.037) were elicited. There was no significant difference between bulbar-dominant and limb-dominant type groups in ‘SCORE’ in both upper and lower limbs. The study showed that the sudomotor dysfunction represented by Q-Sweat is statistically correlated with functional status of patients with ALS. Patients have decreased function of regulating sweat responses as the disease progresses and are susceptible to skin damage or aspiration by saliva. Sudomotor dysfunction can deteriorate functional status of patients and the degree of this issue can be easily quantified by Q-Sweat.

T130. Quantitative sudomotor axon reflex testing in anterior horn cell disorders

Autonomic disturbances in the form of hyperhidrosis, stiffness of fingers and aggravation of motor weakness on exposure to cold(Cold paresis) has been reported in anterior horn cell disorders like early stages of Amyotrophic lateral sclerosis (ALS), Brachial Monomelic Amyotrophy (BMMA) and Distal Bimelic Amyotrophy (DBMA). Quantitative sudomotor axon reflex test (QSART) was done to assess the functional integrity of postganglionic sympathetic sudomotor axons. 25 patients of BMMA, 10 patients with DBMA divided into two groups based on age (Group1: 20–30 years and Group2: 30–40 years) and 10 patients with ALS where recruited for the study and compared with equal cohort of age matched controls. General physical examination and anthropometric measurements were taken before recording. Sudomotor function of the study participants were evaluated by using Q-Sweat device manufactured by WR Medical Electronics. Resting sweat rate was recorded 5 min followed by iontophoretic stimulation. Baseline sweat volume, Total sweat volume and latency time from start of iontophoretic stimulation [acetylcholine-2 mA current strength for 5 min] to sweat response from 4 recording sites were measured. The variances in parameters like age, body weight, both height of both control and disease group were not significantly different and hence comparable. The mean age of BMMA patients: [Group1: 22.8 ± 3.8 and Group2: 33.8 ± 3.2 years] age matched controls - [Group1: 25.4 ± 2.7 and Group2: 35.1 ± 2.8 years]. There was no significant difference in baseline line sweat rate, latency and total sweat volume between controls and patients at four sites viz. Forearm, Proximal leg, Distal leg and Foot in both affected and unaffected limb. There was no significant difference between affected and unaffected limbs in above parameters in patients with BMMA. Similar results were obtained for patients in early stages of ALS (mean age 46.8 ± 3.2 years) and DBMA [Group1: 23.3 ± 4.8 and Group2: 38.0 ± 2.9 years]. Our findings suggests normal functioning of post ganglionic sudomotor fibers in BMMA and DBMA. The highly prevalent autonomic symptoms probably arise due to pre-ganglionic autonomic dysfunction and possibly in the cervical cord.

Orthostatic tachycardia with different onset time in patients with orthostatic intolerance

ObjectiveTo investigate whether there is a difference in the neuro-autonomic and hemodynamic parameters in patients with postural tachycardia syndrome (POTS) according to onset time of orthostatic tachycardia during the Head-up tilt (HUT) test. MethodsWe retrospectively reviewed neuro-autonomic and hemodynamic data from patients with orthostatic intolerance. A standardized battery of neuro-autonomic tests, including the HUT, Valsalva maneuver, heart rate deep breathing and quantitative sudomotor axon reflex test, was performed. The beat-to-beat derived hemodynamic parameters, including systolic blood pressure (BP) (SBP), mean BP (MBP), diastolic BP, heart rate (HR), total peripheral resistance, stroke volume, and cardiac output, were also extracted from HUT test. According to onset time of orthostatic tachycardia (OT), we divided patients into two groups; HR increase “within 10 minutes” (i.e., early OT) and HR increase “after 10 minutes” (i.e., late OT). ResultsWe identified 210 patients with OT during HUT test. Forty-three percent of patients were included in early OT group and 57% were late OT group. Patients in late OT group were older than early OT group. Late OT group tended to have baseline hypertension more frequently compared to early OT group. After adjusting for age, late OT group showed higher baseline SBP and MBP, and lower increase of HR during HUT test than early OT group. However, other neuro-autonomic and hemodynamic parameters did not show significant differences between two groups. ConclusionOrthostatic tachycardia might be developed in the late period during the HUT test. There were no remarkable differences in neuro-autonomic and hemodynamic parameters between early and late OT groups. It seems reasonable to extend the duration of HUT test to at least 20 min, to increase the diagnostic yield in patients with a history of orthostatic intolerance suspected as having POTS.

O164 Different patterns of dysautonomia in relapsing and progressive multiple sclerosis

Objectives To determine differences in autonomic dysfunction in patients with relapsing remitting multiple sclerosis (RMMS) and progressive forms of MS (PMS). Methods Forty RRMS (33 females,35.45 ± 9.15, median EDSS 1.25, median disease duration 923 days) and 30 PPMS (17 females, 48.03 ± 10.58, median EDSS 6.5, median disease duration 4538 days) patients were enrolled. The following autonomic tests were performed: heart rate and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing (RSA), blood pressure response to passive tilt and Quantitative Sudomotor Axon Reflex Test (QSART). All tests were interpreted in the form of the composite autonomic scoring scale (CASS). Results Median CASS was 1 (range 0 to 5) and 3 (range 0 to 6) for RRMS and PMS patients, respectively. Patients with PMS had significantly higher adrenergic, cardiovagal, sudomotor indices and total CASS compared to patients with RRMS (p = 0.029, p = 0.018, p 0.001 and p 0.001 , respectively). Disease duration positively correlated with adrenergic, cardiovagal, sudomotor indices and total CASS (rs = 0.294, p = 0.02; rs = rs = 0.275, p = 0.027; rs = 0.409, p 0.001 and rs = 0.472, p 0.001 , respectively). EDSS positively correlated with cardiovagal and sudomotor indices and total CASS (rs = 0.264, p = 0.033; rs = 0.411, p 0.001 and rs = 0.402, p = 0.001, respectively). Discussion Autonomic function is rarely investigated in MS, although it may have an impact on several important aspects like fatigue, exercise capacity and MS specific medication tolerance. Conclusion Autonomic dysfunction is more prevalent in progressive MS compared to RRMS. Significance Autonomic dysfunction in MS correlates well with the EDSS and disease duration.

A model for in vivo analysis of sudomotor sympathetic C-fiber activation and human sweat gland output.

Quantitative assessment of small-fiber peripheral neuropathy often involves an evaluation of the interaction between the C-fiber sudomotor nerve and local sweat rate (SR). Typically, some sort of quantitative sudomotor axon reflex test (QSART) is performed to aid in diagnosing small-fiber dysfunction. The currently used QSART demonstrates only moderate test-retest reliability and therefore limits its usefulness in tracking small-fiber dysfunction. A new experimental model to examine small C-fiber function in the skin using intradermal electrical stimulation and simultaneous monitoring of SR is proposed. Using intradermal electrical stimulation (1.5 and 2.5 mA) and varying stimulus frequency from 0.2 to 64 Hz, a quantitative relationship between the area under the SR-time curve and log10 stimulus frequency is modeled using a four-parameter logistic equation, providing the following parameters: baseline, plateau, EC50, and Hill slope. The model has good to excellent repeatability within the same day (ICC = 0.98), on different days at the same skin site (ICC = 0.80), and when comparing two different skin sites (ICC = 0.78) with a small bias estimate and the line of identity always lying within the 95% limits of agreement. Atropine sulfate (0.1 mg/ml) blocked 90 ± 5% of the electrically induced sweating. Overall, the model provides control over sudomotor nerve activity and a quantitative assessment of SR. Finally, the ability to reproduce the quantitative stimulus-response curve on different days allows for a robust assessment of the relationship between the activation of a sympathetic C-fiber and local SR.NEW & NOTEWORTHY A model for quantitative assessment of C-fiber function in human skin using intradermal electrical stimulation and local sweat rate measurements has been developed. This new electrically induced sweating model is nonpainful and allows for a complete stimulus-response curve plotting the area under the local sweat rate-time curve vs. the log10 stimulus frequency. The model has good reproducibility and should provide a means of assessing the progression of small C-fiber peripheral neuropathy in humans.

Application of electrophysiological test in prediabetic peripheral neuropathy

Early diagnosis of prediabetic peripheral neuropathy depends on the evaluation of small fibers. Traditional nerve conduction tests can only evaluate the function of large myelinated fibers, while lack of sensitivity to small fibrous lesions. These lesions were related to pain and autonomic neuropathy. In recent years, with the progress of neurophysiological diagnosis technology, the early diagnosis of diabetic peripheral neuropathy has been improved. Clinical methods, commonly used in the detection of small fibrous lesions, mainly include skin sympathetic response, quantitative sensory test, contact heat pain evoked potential, and quantitative sudomotor axonal reflex test. In this paper, the pathogenesis of diabetic peripheral neuropathy, neurological pathological changes and applications of electrophysiology technology were reviewed to provide an objective basis for early diagnosis of prediabetic peripheral neuropathy. Key words: Electrophysiological test; Prediabetes; Peripheral neuropathy

Diagnostic Criteria for Small Fiber Neuropathy.

Despite its relative common occurrence, definitive diagnosis of small fiber neuropathy (SFN) remains problematic. In practice, patients with pain, numbness, and/or paresthesias in their lower limbs are diagnosed with SFN if found to have dissociated sensory loss in their feet, that is, impaired pinprick perception (PP) but relatively preserved vibration. We sought to assess the sensitivity and specificity of clinical examination and various diagnostic tools available for screening SFN. Medical records of 56 patients diagnosed with SFN were reviewed. Diagnosis was based on symptoms, detailed neurological examination that included PP, and abnormal results on at least one testing modality-quantitative sudomotor axon reflex (sweat) test (QSART), quantitative sensory testing (QST), and heart rate variability (HRV) testing. Sensitivity of PP was relatively consistent between modalities of about 63% in presence of appropriate sensory symptoms. Laboratory testing diagnosed 88% of patients when both QSART and QST are employed. QST was most sensitive for detection of SFN with the heat-pain testing having higher sensitivity than cooling. Heart rate variability testing revealed low correlation across all groups. The diagnostic yield for SFN increases by combining clinical features with various testing modalities. In symptomatic patients, we propose the following diagnostic criteria for diagnosis of SFN: Definite SFN-abnormal neurological examination and both QSART and QST; Probable SFN-abnormal neurological examination, and either QSART or QST; Possible SFN-abnormal neurological exam, QSART, or QST.

Comparison of Somatic and Sudomotor Nerve Fibers in Type 2 Diabetes Mellitus.

Background and PurposeThe objective of this study was to find a sensitive method for the early detection of diabetic polyneuropathy (DPN) and determine the relationship between the functions of somatic and autonomic small nerve fibers in DPN.MethodsPatients with type 2 diabetes mellitus and DPN based on clinical symptoms, signs, intraepidermal nerve fiber density (IENFD), and findings in the quantitative sudomotor axon reflex test (QSART) were enrolled retrospectively. Neurological examinations and nerve conduction studies were performed on all patients. Heart-rate variability during deep breathing (DB ratio) and the Valsalva maneuver (Valsalva ratio) were used to quantify the cardiovagal function. Patients were divided into two groups: 1) normal nerve conduction, defined as small-fiber neuropathy (SFN) and 2) abnormal nerve conduction, defined as mixed-fiber neuropathy.ResultsIn total, 82 patients were enrolled (age: 60.7±10.7 years, mean±SD). A decreased IENFD was the most frequent abnormality across all of the patients, followed by abnormalities of the QSART and cardiovagal function. A decreased IENFD was more sensitive than the QSART, DB ratio, and Valsalva ratio for detecting diabetic SFN. The DB ratio was significantly correlated with the duration of diabetes mellitus and clinical symptoms and signs. There was no correlation between the IENFD and the findings of the QSART for the distal leg.ConclusionsMeasuring the IENFD was a more sensitive method than the QSART for the early detection of DPN. The degree of involvement of the somatic small nerve fibers and sudomotor nerve fibers was independent in DPN.

Demonstration of autonomic dysfunction in traumatic brachial plexus injury using quantitative sudomotor axon reflex test: Preliminary results.

To objectively document autonomic dysfunction in the affected arm with traumatic brachial plexus injury (TBPI) using quantitative sudomotor axon reflex test (QSART). Patients with TBPI presenting to the neurosurgical outpatient department from August 2013 to November 2014 were included in the study. The QSART was administered to each patient with prior informed consent detailing the procedure. A total of 20 patients with TBPI were included in the study. The age, sex, mode of injury, date of injury, side of injury, and type of injury (pan brachial plexus vs preserved distal function) were recorded. The presence of any pain was also recorded. The injuries were also grouped as preganglionic and postganglionic injuries based on clinical, electroneuromyography (ENMG) and magnetic resonance imaging (MRI) findings. The results of the test for the affected and normal limb were recorded and analyzed with appropriate statistical tests to determine any significant differences. The study included 20 patients, with their age ranging from 15 to 50 years. Out of the 20 patients, one was female and the rest 19 were males. Seven (35%) of the injuries were complete (pan brachial plexus) and 13 (65%) were incomplete (preserved distal function). All patients had preganglionic TBPI. There was no evidence of any statistically significant difference between the affected and normal arm for total sweat volume (P = 0.20) and latency period (P = 0.42). However, the average mean values for the same were lower in the affected arm as compared to the normal. The baseline sweat output (P = 0.010), however, was significantly lower in the affected arm as compared to the normal arm. QSART has demonstrated reduced baseline sweat output in the affected arm in patients with TBPI. This indicates the presence of autonomic dysfunction in the injured arm.

Association Between Metabolic Syndrome Components and Polyneuropathy in an Obese Population

ImportancePast studies have shown an association between metabolic syndrome and polyneuropathy, but the precise components that drive this association remain unclear.ObjectivesTo determine the prevalence of polyneuropathy stratified by glycemic status in well-characterized obese and lean participants and investigate the association of specific components of metabolic syndrome with polyneuropathy.Design, Setting, and ParticipantsWe performed a cross-sectional, observational study from November 1, 2010, to December 31, 2014, in obese participants (body mass index [calculated as weight in kilograms divided by height in meters squared] of 35 or more with no comorbid conditions or 32 or more with at least 1 comorbid condition) from a weight management program and lean controls from a research website. The prevalence of neuropathy, stratified by glycemic status, was determined, and a Mantel–Haenszel χ2 test was used to investigate for a trend. Logistic regression was used to model the primary outcome of polyneuropathy as a function of the components of metabolic syndrome after adjusting for demographic factors. Participants also completed quantitative sudomotor axon reflex testing, quantitative sensory testing, the neuropathy-specific Quality of Life in Neurological Disorders instrument, and the short-form McGill Pain Questionnaire.ExposuresComponents of metabolic syndrome (as defined by the National Cholesterol Education Program Adult Treatment Panel III), including glycemic status (as defined by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus).Main Outcomes and MeasuresToronto consensus definition of probable polyneuropathy. Secondary outcomes included intraepidermal nerve fiber density and nerve conduction study parameters.ResultsWe enrolled 102 obese participants (mean [SD] age, 52.9 [10.2] years; 48 men and 54 women; 45 with normoglycemia [44.1%], 31 with prediabetes [30.4%], and 26 with type 2 diabetes [25.5%]) and 53 lean controls (mean [SD] age, 48.5 [9.9] years; 16 men and 37 women). The prevalence of polyneuropathy was 3.8% in lean controls (n = 2), 11.1% in the obese participants with normoglycemia (n = 5), 29% in the obese participants with prediabetes (n = 9), and 34.6% in the obese participants with diabetes (n = 9) (P < .01 for trend). Age (odds ratio, 1.09; 95% CI, 1.02-1.16), diabetes (odds ratio, 4.90; 95% CI, 1.06-22.63), and waist circumference (odds ratio, 1.24; 95% CI, 1.00-1.55) were significantly associated with neuropathy in multivariable models. Prediabetes (odds ratio, 3.82; 95% CI, 0.95-15.41) was not significantly associated with neuropathy.Conclusions and RelevanceThe prevalence of polyneuropathy is high in obese individuals, even those with normoglycemia. Diabetes, prediabetes, and obesity are the likely metabolic drivers of this neuropathy.Trial Registrationclinicaltrials.gov Identifier: NCT02689661.

Electrochemical Skin Conductance Correlates with Skin Nerve Fiber Density.

Purpose: Electrochemical skin conductance (ESC) using reverse iontophoresis and chronoamperometry has been used to evaluate abnormal function of small fibers. How ESC correlates with loss of small fibers in skin is unclear.Methods: This was a prospective, blinded study. The primary outcome measure was the correlation between ESC at the feet and results of skin biopsies including epidermal nerve fiber density (ENFD) and sweat gland nerve fiber density (SGNFD) at the distal leg. ESC, ENFD, and SGNFD data were normalized by adjusting for weight. The secondary outcome measures were the correlation between ESC and the following variables: quantitative sudomotor axon reflex test (QSART) and symptom scales (neuropathy, pain and autonomic).Results: Eighty-one patients (mean ± sd): age = 53.3 ± 17.3, men/women = 25/56 were enrolled in the study. ESC was reduced in subjects with abnormally low ENFD (ENFD normal/abnormal, ESC = 1.17 ± 0.27/0.87 ± 0.34 μSiemens/kg, p < 0.0008) and abnormally low SGNFD (SGNFD normal/abnormal ESC = 1.09 ± 0.34/0.78 ± 0.3 μSiemens/kg, p < 0.0003). ESC correlated with ENFD (ρ = 0.73, p = 0.0001) and SGNFD (ρ = 0.64, p = 0.0001). ESC did not correlate with symptom scales.Conclusion: ESC is diminished in subjects who have a reduced number of small fibers in the skin and the ESC reduction is proportional to ENFD and SGNFD. ESC can be useful in detecting loss of small nerve fibers.

Detailed Relationship Between the Pattern of Blood Pressure Change During the Valsalva Maneuver and the Degree of Orthostatic Hypotension During the Head-Up Tilt Test in Patients With Orthostatic Intolerance: A Retrospective Case-Control Study.

Although the head-up tilt (HUT) test and Valsalva maneuver (VM) have been widely used to identify sympathetic adrenergic impairment, the detailed relationship between the degree of orthostatic hypotension (OH) during the HUT test and the pattern of blood pressure (BP) change during the VM remains unknown. This study was performed to investigate the relationship between the degree of OH during the HUT test and the pattern of BP change during the VM. During a 4-year period, a total of 132 consecutive patients with neurogenic OH and 60 healthy controls were enrolled. The degree of OH was defined as mild (associated with a fall in systolic BP [SBP] ≥ 20 < 30 on tilting, n = 49), moderate (associated with a fall in SBP ≥ 30 < 40 on tilting, n = 43), and severe (associated with a fall in SBP ≥ 40 on tilting, n = 40). A standardized battery of autonomic tests, including the HUT test and VM using Finometer devices for recording beat-to-beat BP and heart rate response, and a quantitative sudomotor axon reflex test, was performed. Sympathetic indexes (SIs 1–6) were calculated from the VM. A composite autonomic severity score (CASS) was also obtained to evaluate the severity and distribution of autonomic dysfunction. The degree of OH was compared with the BP decline and recovery during the VM. All indexes exhibited overall significant differences among tested groups (P < 0.001). Only SI 3 differentiated all subject groups. Compared with other SIs, SI 3 was best correlated with the amount of decrease in the mean SBP (R2 = 0.473, P < 0.001) on tilting. The decrease in mean SBP on tilting was best correlated with CASS adrenergic subscore. SI 3 can differentiate between groups with different degrees of OH. The SI 3 obtained during VM can improve the diagnostic accuracy of autonomic dysfunction in patients with different degree of OH.