Composite Autonomic Scoring Scale Research Articles

Baroreflex Sensitivity as a Surrogate Biomarker for Concurrently Assessing the Severity of Arterial Stiffness and Cardiovascular Autonomic Neuropathy in Individuals with Type 2 Diabetes.

This study aimed to investigate whether baroreflex sensitivity (BRS) could serve as a reliable metric for assessing cardiovascular autonomic neuropathy (CAN) and concurrently act as a surrogate biomarker for evaluating the severity of arterial stiffness and CAN in individuals diagnosed with type 2 diabetes mellitus (T2DM). Participants underwent brachial-ankle pulse wave velocity (baPWV) as well as autonomic function evaluations encompassing the Sudoscan-based modified composite autonomic scoring scale (CASS), baroreflex sensitivity, and heart rate variability in time domains and frequency domains. Linear regression analysis was performed to evaluate the influence of independent variables on baPWV and modified CASS. Participants with higher baPWV values were older, with longer diabetes duration, lower body weight, body mass index, waist circumference, elevated systolic and diastolic blood pressure, and mean arterial blood pressure. They also exhibited a higher prevalence of retinopathy as the underlying disease and reduced estimated glomerular filtration rate. Multiple linear regression analysis revealed that age and BRS were significantly associated with baPWV while diabetes duration, UACR, and BRS were significantly associated with modified CASS. Our study confirms the significant association of BRS with baPWV and modified CASS in T2DM, highlighting its pivotal role in linking microvascular and macrovascular complications. This supports BRS as a surrogate marker for assessing both the severity of arterial stiffness and cardiovascular autonomic neuropathy in T2DM, enabling the early identification of complications.

The Effects of Autonomic Dysfunction on Functional Outcomes in Patients with Acute Stroke.

Autonomic dysfunction is a common complication of acute stroke, which impairs functional outcomes and increases mortality. There is a lack of well-established knowledge regarding the influence of autonomic dysfunction in patients with acute stroke. This study aims to investigate the impact of the severity of autonomic dysfunction on functional outcomes in patients with acute stroke. A retrospective analysis was conducted at a single center, involving 22 patients diagnosed with acute stroke. The severity of autonomic dysfunction was evaluated based on the Composite Autonomic Scoring Scale (CASS). The modified Barthel Index, Berg Balance Scale, Functional Ambulatory Category, and modified Rankin Scale were designated as functional outcome measures. The impact of the severity of autonomic dysfunction on functional outcomes was analyzed using one-way analysis of covariance (ANCOVA). A statistically significant difference was observed between the initial and follow-up functional outcomes based on the severity of autonomic dysfunction. This study presents evidence that the severity of autonomic dysfunction influences functional prognosis in patients with acute stroke. The findings will serve as additional considerations for the rehabilitation of patients with acute stroke.

Impacts of Chemerin Levels and Antioxidant Capacity on the Severity of Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes and Prediabetes.

Existing evidence supports an association between chemerin levels and cardiovascular risk, while reduced thiol levels are linked to diabetes mellitus. It is hypothesized that chemerin may contribute to autonomic dysfunction and cardiovascular risk in type 2 diabetes mellitus (T2DM), potentially mediated by the antioxidant capacity of patients with well-controlled T2DM and prediabetes. Comprehensive cardiovascular autonomic testing and biomarker assessments were conducted for all participants. The severity of cardiovascular autonomic neuropathy (CAN) was evaluated using the composite autonomic scoring scale (CASS). A mediation model was employed to explore the potential relationships among chemerin levels, antioxidant capacity (indicated by thiol levels), and CAN severity (indicated by CASS values). A total of 184 participants were enrolled in this study, comprising 143 individuals with T2DM and 40 individuals with prediabetes. The findings reveal a significant negative association between thiols levels (r = -0.38, p < 0.0001) and the CASS values, while a positive association is observed between chemerin levels (r = 0.47, p < 0.0001) and the CASS values. Linear regression analysis identified chemerin and thiols as independent variables significantly associated with CASS values. Subsequent mediation analysis elucidated that thiols levels act as mediators in the relationship between elevated chemerin levels and an increased CASS value. This study shows that poor cardiovascular function, higher chemerin levels, and reduced antioxidant capacity coexist in individuals with T2DM and prediabetes. Mediation analysis suggests a pathophysiological link between high chemerin levels and low antioxidant capacity, adversely impacting CAN severity.

Sudoscan as substitute for quantitative sudomotor axon reflex test in composite autonomic scoring scale and its correlation with composite autonomic symptom scale 31 in type 2 diabetes

ObjectiveThis study aims to evaluate the feasibility of substituting electrochemical skin conductance measurement using SUDOSCAN for sudomotor function testing in the Composite Autonomic Scoring Scale (CASS) and to correlate the results with the Composite Autonomic Symptom Scale 31 (COMPASS 31) among patients with type 2 diabetes mellitus (T2DM). MethodsFifty patients with T2DM underwent cardiovascular autonomic function testing and the SUDOSCAN test and completed the COMPASS 31 questionnaire. We developed a SUDOSCAN-based sudomotor subscore as a substitute for the original sudomotor subscore (based on the quantitative sudomotor axon reflex test [QSART]). The modified CASS score (SUDOSCAN-based sudomotor subscore combined with the adrenergic and cardiovagal subscores) and the original CASS score without suomotor assessment (sum of the adrenergic and cardiovagal subscores) were obtained according to the results of the cardiovascular autonomic function and SUDOSCAN tests. ResultsThe total COMPASS 31 score was significantly correlated with the modified CASS score (p = 0.019 and 0.037 for the raw and weighted scores, respectively) but not with the CASS score without sudomotor assessment. After adding the SUDOSCAN-based sudomotor subscore, the number of patients identified as having diabetic autonomic neuropathy (DAN) increased from 24 (48 %, based on the CASS score without sudomotor assessment) to 35 (70 %, based on the modified CASS score). The modified CASS score enhances the accuracy of assessing autonomic function and improves the diagnosis of diabetic autonomic neuropathy (DAN) among patients with T2DM. In medical settings where QSART is not accessible, SUDOSCAN testing offers a practical and efficient alternative.

Assessing the Feasibility of Using Electrochemical Skin Conductance as a Substitute for the Quantitative Sudomotor Axon Reflex Test in the Composite Autonomic Scoring Scale and Its Correlation with Composite Autonomic Symptom Scale 31 in Parkinson’s Disease

The Composite Autonomic Scoring Scale (CASS) is a quantitative scoring system that integrates the sudomotor, the cardiovagal, and the adrenergic subscores, and the Composite Autonomic Symptom Scale 31 (COMPASS 31) is based on a well-established comprehensive questionnaire designed to assess the autonomic symptoms across multiple domains. We tested the hypothesis that electrochemical skin conductance (Sudoscan) can be a substitute for the quantitative sudomotor axon reflex test (QSART) in the sudomotor domain and assessed its correlation with COMPASS 31 in patients with Parkinson's disease (PD). Fifty-five patients with PD underwent clinical assessment and cardiovascular autonomic function tests and completed the COMPASS 31 questionnaire. We compared the modified CASS (integrating the Sudoscan-based sudomotor, adrenergic, and cardiovagal subscores) and CASS subscores (the sum of the adrenergic and cardiovagal subscores). The total weighted score of COMPASS 31 was significantly correlated with both the modified CASS and the CASS subscore (p = 0.007 and p = 0.019). The correlation of the total weighted score of COMPASS 31 increased from 0.316 (CASS subscores) to 0.361 (modified CASS). When we added the Sudoscan-based sudomotor subscore, the case numbers for autonomic neuropathy (AN) increased from 22 (40%, CASS subscores) to 40 (72.7%, modified CASS). The modified CASS not only better reflects the exact autonomic function, but also improves the characterization and quantification of AN in patients with PD. In areas in which a QSART facility is not easily available, Sudoscan could be a time-saving substitution.

Autonomic impairment in treatment-naive patients with chronic hepatitis B and C infections.

Peripheral neuropathy is not an uncommon manifestation in patients with chronic hepatitis. The role of cryoglobulin (CG) in neuropathy in patients with chronic hepatitis remains controversial. There is limited information about the autonomic neuropathy in chronic hepatitis. This study aimed to evaluate autonomic function in treatment-naive patients with chronic hepatitis B or hepatitis C infection and to elucidate the association between autonomic neuropathy and CG in these patients. A total of 29 treatment-naive patients with chronic, yet mild degrees of hepatitis B or C infection were evaluated for autonomic function, including those in the sympathetic sudomotor, cardiovagal, and adrenergic domains, to compare with the control subjects. The autonomic impairment was graded using the Composite Autonomic Scoring Scale. Then, association analyses between autonomic parameters/scores and CG were performed. Patients with chronic hepatitis B or C infection had significantly worse autonomic function than control subjects, especially in the sudomotor and cardiovagal domains. The autonomic manifestations in cases with and without CG were similar. There was no significant difference in autonomic dysfunction between patients with hepatitis B and C infections. The study demonstrated that autonomic neuropathy was not uncommon in patients with chronic hepatitis B or C infection. There was no association between autonomic neuropathy and CG.

Effectiveness of Different Methods for Baroreflex Sensitivity Assessment in Determining the Severity of Cardiovascular Autonomic Neuropathy in Patients With Parkinson's Disease.

BackgroundAutonomic disorders are an important non-motor feature of Parkinson’s disease (PD). Baroreflex sensitivity (BRS) is often used as an indicator of cardiovascular autonomic function, and it is clinically significant. Several different methods of BRS assessment have been described. We evaluated and compared the efficiency of several methods of BRS assessment for additional insight into the underlying physiology and the determination of its severity in patients with PD.Materials and MethodsEighty-five patients with PD underwent cardiovascular autonomic testing. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment and to define the presence of cardiovascular autonomic neuropathy (CAN). BRS was assessed using the Valsalva maneuver (BRS_VM). In addition, spontaneous BRS was computed using the sequence method and the spectral method.Results and ConclusionThere was considerable agreement between the different methods of BRS assessment. Nevertheless, BRS_VM exhibited a higher degree of correlation with cardiovascular autonomic function than spontaneous BRS indexes obtained by the sequence or spectral method. BRS_VM, rather than spontaneous BRS, also had a predictive value for the presence of CAN to the diagnostic criteria by CASS in patients with PD.

Clinical Assessment Scales in Autonomic Nervous System Disorders

The autonomic nervous system plays an important role in maintaining homeostasis mediated by the parasympathetic, sympathetic and enteric systems. Autonomic failure adversely affects body function and may increase morbidity and mortality. Therefore, the scoring systems, such as Ewing’s classification and Composite Autonomic Scoring Scale (CASS), were developed to detect and quantify autonomic deficits, primarily focusing on the cardiovascular reflex system. Autonomic disorders manifest with a myriad of symptoms resulting from the dysfunction of the gastrointestinal, genitourinary, secretomotor, pupillomotor systems as well as cardiovascular system. Several self-report questionnaires, such as Composite Autonomic Symptom Scale (COMPASS), Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms (SCOPA-AUT), Survey of Autonomic Symptom (SAS), were also used to support to detect various signs and symptoms of autonomic dysfunction in clinical settings. In this review, we introduce clinically useful assessment scales in autonomic nervous system disorders.

The Role of Electrochemical Skin Conductance as a Screening Test of Cardiovascular Autonomic Neuropathy in Patients with Parkinson's Disease.

Autonomic disorders have been recognized as an important non-motor feature in Parkinson’s disease (PD). However, there is a paucity of information on the presence and severity of cardiovascular autonomic neuropathy (CAN) among different motor phenotypes. The aims of this study were to examine the feasibility of electrochemical skin conductance (ESC) measured by Sudoscan as a screening service for CAN in patients with PD and investigate the severity of CAN among different motor phenotypes. Design: This was a cross-sectional observational study that enrolled 63 patients with PD. Patients were divided into three phenotypes, postural instability/gait difficulty (PIGD), tremor-dominant (TD), and akinetic-rigid (AR), according to their motor symptoms. Cardiovascular autonomic function was measured, and the presence and severity of CAN was determined according to the composite autonomic scoring scale (CASS). Functional scores were measured by the Hoehn and Yahr (HY) stage and the Unified Parkinson’s Disease Rating Scale (UPDRS). The median HY stage was 2.0 [1.5, 3.0]. Median UPDRS total score was 23.0 (17.5, 30.5), 10.0 (6.0, 11.0) and 14.0 (6.3, 23.8) in groups of PIGD, TD and AR, respectively (p = 0.001). Mean CASS was 1.7 ± 1.3, 0.6 ± 0.4, and 1.8 ± 1.5 in groups of PIGD, TD and AR, respectively (p = 0.204). Although the ESC was not strongly associated with the cardiovascular autonomic parameters, the CAN risk score provided by Sudoscan significantly correlated with parameters of cardiovascular autonomic function, including heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS). By receiver-operating characteristic (ROC) analysis, if a patient’s CAN risk score is higher than 33.5 (%), it is recommended to be aware of the presence of CAN even in PD patients who are asymptomatic. The area under ROC curve was 0.704. Based on our results, CAN risk score may be used for screening of CAN in patients with PD before resorting to the more sophisticated and specific, but ultimately more time-consuming, complete autonomic function testing.

Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes

BackgroundEvidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes.MethodsThe complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value).ResultsA total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS.ConclusionsOur results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.

Severity of Cardiovascular Autonomic Neuropathy Is a Predictor Associated With Major Adverse Cardiovascular Events in Adults With Type 2 Diabetes Mellitus: A 6-Year Follow-up Study

ObjectivesCardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke). MethodsIn this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE. ResultsThe overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio. ConclusionsBesides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting.

Clinical and MRI correlates of autonomic dysfunction in neuromyelitis optica spectrum disorder

BackgroundThe aim of this study was to investigate the relationship of autonomic dysfunction and clinical findings in patients with neuromyelitis optica spectrum disorder (NMOSD). MethodsFor the assessment of autonomic dysfunction, heart rate variability (HRV) and blood pressure (BP) measurement to deep breathing, Valsalva maneuver or head tilt-table test, with quantitative sudomotor axon reflex test (QSART) were used and interpreted in the form of the composite autonomic scoring scale (CASS). Clinical and radiological correlates with autonomic profiles were analyzed. ResultsA total of 27 patients (mean age, 44.4 ± 12.26 years; female: male=22:5) were enrolled in this study and 74.1% of them showed autonomic dysfunction, involving the adrenergic, cardiovagal, or sudomotor domains. Eighteen patients were during remission, in whom, demographics and MRI findings were associated with an index or a total score of CASS. The presence of cervical cord lesion showed the association with cardiovagal index (B = 0.750, S.E. 0.242, 95% CI 0.237–1.263, p = 0.007), male gender with sudomotor index (B = 1.600, S.E. 0.653, 95% CI 0.199–3.001, p = 0.028) and the involvement of brain and/or spinal cord with a total CASS score (B = 1.500, S.E. 0.655, 95% CI 0.096–2.904, p = 0.038). In multivariable analysis, delayed pressure recovery time showed a significant positive association with EDSS score (B = 0.103, S.E. 0.031, 95% CI 0.037–0.168, p = 0.004). DiscussionCardiovascular and sudomotor autonomic dysfunction are common in NMOSD. Several clinical and MRI characteristics of patients may warrant the investigation of autonomic dysfunction and its proper management.

Longitudinal assessment of autonomic nervous system in patients with first demyelinating event suggestive of multiple sclerosis.

As a high proportion of people with clinically isolated syndrome (pwCIS) exhibit sympathetic adrenergic and sudomotor dysfunction, the aim of this study was to investigate the evolution of autonomic nervous system (ANS) abnormalities in pwCIS over a 2-year follow-up. This was a prospective cohort study in which 121 pwCIS were enrolled and followed for 2years. After 2-year follow-up, data were available for 84 pwCIS. ANS symptoms were evaluated with the Composite Autonomic System Score-31 (COMPASS-31) and results of the ANS tests were expressed using the Composite Autonomic Scoring Scale (CASS) at baseline and visit at month 24. Symptomatic dysautonomia was defined if the patient had a COMPASS-31 value above the median of the whole cohort at baseline evaluation (COMPASS-31>6.79) and CASS score >0. Complete CASS data at baseline and month 24 were available for 62 patients; in 24 (38.7%) patients there was worsening, in 16 (25.8%) there was improvement and in 22 (35.5%) there was no change in CASS score. In 90% of pwCIS (72 of 80) there was no change in parasympathetic nervous system tests, whereas 47.3% (35 of 74) had either worsening or improvement in sympathetic adrenergic and 28.6% (20 of 70) had either worsening or improvement in sudomotor function. A multivariable regression model identified the total number of T2 lesions as an independent predictor for worsening of symptomatic dysautonomia. No predictors for worsening or improving of CASS score were identified. A substantial proportion of pwCIS experienced worsening of ANS abnormalities during the 2-year follow-up and magnetic resonance imaging parameters seemed to predict these abnormalities.

P63-T Longitudinal assessment of autonomic nervous system in patients with first demyelinating event suggestive of MS

Background The aim of this study was to investigate the evolution of autonomic nervous system (ANS) abnormalities in people with clinically isolated syndrome (pwCIS) over a two-year follow-up. Material and methods This was a prospective cohort study in which 121 pwCIS were enrolled and followed for two years. After two-year follow-up, data were available for 84 pwCIS. ANS symptoms were evaluated with the Composite Autonomic System Score-31 (COMPASS-31) and results of the ANS tests were expressed using the Composite Autonomic Scoring Scale (CASS) at baseline and month 24 visits. Symptomatic dysautonomia was defined if the patient had COMPASS-31 value above the median of the whole cohort at baseline evaluation (COMPASS-31 > 6.79) and CASS score greater than 0. Results Complete CASS at baseline and M24 was available for 62 patients, in 24 (38.7%) patients there was worsening, in 16 (25.8%) improvement and in 22 (35.5%) there was no change in CASS. A multivariable regression model identified total number of T2 lesions as independent predictor for worsening of symptomatic dysautonomia. Although not reaching significance there was a trend of cervical spinal cord lesions as independent predictor for CASS worsening and age for CASS improvement (p = 0.058 and p = 0.051, respectively). Conclusion Substantial proportion of pwCIS experience worsening of ANS abnormalities during the two-year follow-up and MRI parameters seems to predict these abnormalities.

P64-T Autonomic symptom burden can predict disease activity in early multiple sclerosis

Background We aimed to evaluate the role of autonomic nervous system (ANS) abnormalities on disease activity (relapses and new MRI lesions) and disease progression in people with clinically isolated syndrome (pwCIS). Methods Out of 121 consecutive pwCIS, data on disease activity and progression after 2.9 (1.4–4.1) years of follow-up was available for 94 pwCIS. Baseline characteristics included MRI parameters, Composite Autonomic System Score-31 (COMPASS-31), Composite Autonomic Scoring Scale and supine and standing levels of epinephrine and norepinephrine. Results Univariable logistic regression analysis revealed three predictors for occurrence of new relapse: COMPASS-31 > 7.32, total number of T2 lesions > 3 and decreasing supine level of epinephrine. The Kaplan-Meier survival analysis has shown that patients with COMPASS-31 > 7.32 have statistically significant lower probability that they will be relapse free (p = 0.013). It has also shown that the relative risk reduction for occurrence of new relapse in participants with COMPASS 7.32 and total number of T2 lesions >3 increase the likelihood and the increasing supine level of epinephrine reduces the likelihood of a relapse. Finally, results of the Cox regression analysis showed, that after controlling for age, sex, total number of T2 lesions > 3 and supine level of epinephrine, the hazard for occurrence of new relapse for participants with COMPASS-31 > 7.32 is 2.7 times that of participants with COMPASS-31 Conclusion This study provides evidence that ANS is an important contributor to development of disease activity in pwCIS.

HbA1C Variability Is Strongly Associated With the Severity of Cardiovascular Autonomic Neuropathy in Patients With Type 2 Diabetes After Longer Diabetes Duration.

BackgroundVariability in the glycated hemoglobin (HbA1c) level is associated with a higher risk of microvascular complications in patients with type 2 diabetes. We tested the hypothesis that HbA1c variability is not only strongly associated with the presence but also the degree of severity of cardiovascular autonomic neuropathy (CAN) in patients with long diabetes durations (more than 10 years).MethodsFor each patient, the intrapersonal mean, standard deviation (SD), and coefficient of variation (CV) for HbA1c were calculated using all measurements obtained 3 years before the study. We constructed the composite autonomic scoring scale (CASS) as a measure of the severity of cardiovascular autonomic functions. Stepwise logistic regression and linear regression analyses were performed to evaluate the presence of CAN and the influence of independent variables on the mean CASS, respectively.ResultsThose with CAN had a higher mean age, a higher low-density lipoprotein cholesterol (LDL-C), HbA1c-SD, HbA1c-CV, mean HbA1c, and index HbA1c, higher prevalence of retinopathy as the underlying disease, and lower high-density lipoprotein (HDL) levels. Stepwise logistic regression showed that HbA1c-SD and retinopathy were risk factors that were independently associated with the presence of CAN. Mean HbA1c, HbA1c-CV, HbA1c-SD, and index HbA1c were positively correlated with mean CASS, and a multiple linear regression analysis revealed that HbA1c-SD was independently associated with the mean CASS.ConclusionHbA1c variability is strongly associated with not only the presence but also the degree of severity of CAN. A longitudinal study is required to confirm whether controlling blood glucose level is effective in reducing CAN progression.

Close relationship between cardiovagal function and sural sensory nerve action potential in type 2 diabetes

ObjectiveBoth diabetic distal symmetrical polyneuropathy (DSPN) and cardiac autonomic neuropathy (CAN) indicate the length-dependent pattern of disease. Decreased parasympathetic activity has been found in the early phase of CAN and sural sensory nerve action potential (SNAP) imply axonal loss in DSPN. MethodAll patients with type 2 diabetes underwent cardiovascular autonomic function and nerve conduction studies (NCS). We constructed modified composite autonomic scoring scale (CASS) and composite score of NCS to measure the severity of CAN and DSPN, respectively. ResultsPatients with a longer duration of diabetes had a lower heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS), higher CASS, a higher percentage of CAN, lower sural SNAP, higher composite score of NCS, and a higher percentage of DSPN. Multiple linear regression analysis showed that only sural SNAPs were independently associated with mean HR_DB. ConclusionSural SNAP was closely correlated with parameters of cardiovagal functions in patients with different durations of diabetes. The percentage and severity of CAN and DSPN increase with longer duration of diabetes. SignificanceThe independent association of sural sensory nerve action potential amplitude and heart rate response to deep breathing with type 2 diabetes is important because combined testing increases diagnostic sensitivity and specificity.

Autonomic dysfunction in people with neuromyelitis optica spectrum disorders

Aims: To determine the difference in autonomic symptom burden measured with the Composite Autonomic System Score-31 (COMPASS-31) and presence of objective dysautonomia in people with neuromyelitis optica spectrum disorders (pwNMOSD) compared to people with multiple sclerosis (pwMS). Design/Methods: Twenty pwNMOSD and 20 pwMS, matched for age, sex, and disease duration, were enrolled. All patients completed the COMPASS-31. The quantification of cardiovascular autonomic dysfunction (CAD) was made using the two indices of the Composite Autonomic Scoring Scale (CASS): adrenergic index (AI) and cardiovagal index (CI). Results: In all pwNMOSD, COMPASS-31 was >0. Sympathetic dysfunction was present in 8 (40%), parasympathetic dysfunction in 10 (50%), and orthostatic hypotension in 6 (30%) pwNMOSD. This group of patients had higher frequency and level on the pupillomotor domain of the COMPASS-31 compared to pwMS (p = 0.048 and p = 0.006, respectively). A binary logistic regression model showed that drop in diastolic blood pressure (dBP) during tilt-table test and normal function of autonomic nervous system, defined as AI = 0 and CI = 0, were independent predictors of pwNMOSD (p = 0.042 and p = 0.029, respectively). If CAD was present, it was significantly worse in pwNMOSD compared to pwMS (p = 0.003). Conclusion: Significant proportion of pwNMOSD experience dysautonomia, which seems to be different from dysautonomia observed in pwMS.

Autonomic symptom burden can predict disease activity in early multiple sclerosis

BackgroundWe aimed to evaluate the role of autonomic nervous system (ANS) abnormalities on disease activity (relapses and new MRI lesions) and disease progression in people with clinically isolated syndrome (pwCIS). MethodsOut of 121 consecutive pwCIS, data on disease activity and progression after 2.9 (1.4–4.1) years of follow-up, was available for 94 pwCIS. Baseline characteristics included MRI parameters, Composite Autonomic System Score-31 (COMPASS-31), Composite Autonomic Scoring Scale, and supine and standing levels of epinephrine and norepinephrine. ResultsUnivariable logistic regression analysis revealed three predictors for occurrence of new relapse, COMPASS-31 > 7.32, total number of T2 lesions > 3 and decreasing supine level of epinephrine. The Kaplan–Meier survival analysis showed that patients with COMPASS-31 > 7.32 have statistically significant lower probability that they will be relapse free (p = 0.013). It has also showed that the relative risk reduction for occurrence of new relapse in participants with COMPASS < 7.32 was 46%. The multivariable regression model confirmed that COMPASS-31 > 7.32 and total number of T2 lesions > 3 increase the likelihood and the increasing supine level of epinephrine reduces the likelihood for a relapse. Finally, results of the Cox regression analysis showed, that after controlling for age, sex, total number of T2 lesions > 3 and supine level of epinephrine, the hazard for occurrence of new relapse for participants with COMPASS-31 > 7.32 is 2.7 times that of participants with COMPASS-31 < 7.32. ConclusionThis study provides evidence that ANS is an important contributor to development of disease activity in pwCIS.

Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure

ObjectiveTo assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. Patients and MethodsWe searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab–seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. ResultsOf 289 patients who met inclusion criteria, 163 (56.4%) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92% specificity and 56% sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25%), a level of at least 0.20 nmol/L had 80% specificity and 59% sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1%). ConclusionGanglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25% or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.