Composite Autonomic Severity Score Research Articles

Optimizing measures of HIV-associated neuropathy.

Distal symmetric polyneuropathy (DSP) is common in HIV and is associated with autonomic impairment. However tools to measure HIV-DSP do not include autonomic indices. We sought to optimize the Total Neuropathy Score (TNS) and the Composite Autonomic Severity Score (CASS) for use in HIV. HIV-infected adults (n = 102) underwent neurologic examination, quantitative sensory testing (QST), nerve conduction studies, and autonomic testing. Modifications of the TNS and CASS were assessed for validity based on correlation with the original measure and internal consistency. The TNS version commonly used in HIV-DSP is valid, but it is improved by elimination of QST and addition of autonomic indices. A modified version of the CASS (M-CASS) which was designed for sensitivity to milder impairment was also valid. A modified TNS that excludes QST and includes autonomic indices is optimal for HIV-DSP. The M-CASS is a valid measure of autonomic impairment in HIV.

Disproportionate pupillary involvement in diabetic autonomic neuropathy.

To study the degree of pupillary impairment in diabetic and non-diabetic autonomic neuropathy. We retrospectively sampled from all patients who underwent comprehensive autonomic testing and infrared pupillometry at UT Southwestern Medical Center. Composite autonomic severity score (CASS) and pupillary indices from the average of at least three pupillary response curves were recorded. We randomly matched patients with diabetic autonomic neuropathy (DAN) and patients with autonomic impairment unrelated to diabetes (non-DAN) based on gender, age (±5years), and CASS (±1 point). We used the paired t test to analyze differences between the groups. We identified 40 patients with DAN and 40 matched controls with non-DAN. M:F ratio was 1:1. Mean CASS was 4.2 and mean age was 62.4years. Six had type I and the rest had type II diabetes mellitus. Both absolute constriction amplitude (ACA) and maximum constriction velocity (MCV) were significantly lower in DAN compared to non-DAN; mean ACA was 0.9mm vs. 1.17mm (p=0.0077) and mean MCV was 2.8 vs. 3.6mm/s (p=0.0039). Severely diminished MCV for age was noted in 48% of diabetic and in only 28% of non-DAN patients. The ACA-corrected time to 75% re-dilation was significantly delayed in DAN vs. non-DAN [mean 3.2 vs. 1.7s/mm (p=0.025)]. A statistically significant decline was noted for both the MCV and ACA with higher cardiovagal subscores among DAN patients. Parasympathetic and sympathetic pupillary dysfunction appears to be a common feature of autonomic impairment in diabetes compared to non-diabetic causes of autonomic impairment.

Autonomic evaluation is independent of somatic evaluation for small fiber neuropathy

BackgroundThe relationship between the autonomic reflex screening test (ARS) and measures of sensory function and structure (quantitative sensory testing (QST) and intraepidermal nerve fiber density (IENFD)) remains uncertain in patients with distal small fiber neuropathy (SFN). The aim of this study was to evaluate the correlations among a range of autonomic (quantitative sudomotor axon reflex test (QSART), cardiovagal and cardio adrenergic tests and the composite autonomic severity score (CASS)) and somatic sensory measures (QST of vibration, cooling and heat-pain thresholds and IENFD). Method122 patients with clinically suspected sensory neuropathy without motor weakness and with normal nerve conduction studies underwent blinded autonomic reflex screening test (ARS), quantitative sensory testing (QST) and skin biopsy (IENFD) for diagnosis of SFN. The relationship between autonomic and somatic sensory measures was assessed. ResultsThere was no association between autonomic function measures (QSART volume, CASS_QSART, CASS_vagal, CASS_adrenergic or total CASS) and small fiber sensory measures (IENFD, cooling or heat-pain thresholds). Weak correlations were noted among some modalities of QST (vibration and cooling thresholds) and IENFD. DiscussionAutonomic and sensory outcomes are independent (complementary) measures of distal SFN, and should where feasible be used concurrently in the evaluation of SFN.

Multiple system atrophy: prognostic indicators of survival.

Neurological and autonomic presentation in multiple system atrophy (MSA) may predict early mortality. Quantification of early autonomic failure as a mortality predictor is lacking. Early neurological and autonomic clinical features were retrospectively reviewed in 49 MSA cases (median age at onset, 56.1 years; 16 women) confirmed by autopsy at Mayo Clinic. When available, the 10-point composite autonomic severity score derived from the autonomic reflex screen provided quantification of the degree of autonomic failure and thermoregulatory sweat test quantitated body surface anhidrosis. Symptoms at onset were autonomic in 50%, parkinsonian in 30%, and cerebellar in 20% of cases. Survival (median [95% confidence interval]) was 8.6 [6.7-10.2] years. Survival was shorter in patients with early laboratory evidence of generalized (composite autonomic severity score ≥ 6) autonomic failure (7.0 [3.9-9.8] vs. 9.8 [4.6-13.8] years; P = 0.036), and early requirement of bladder catheterization (7.3 [3.1-10.2] vs. 13.7 [8.5-14.9] years; P = 0.003) compared with those without these clinical features. On Cox proportional analysis, prognostic indicators of shorter survival were older age at onset (hazard ratio [95% confidence interval], 1.04 [1.01-1.08]; P = 0.03), early requirement of bladder catheterization (7.9 [1.88-38.63]; P = 0.004), and early generalized (composite autonomic severity score ≥ 6) autonomic failure (2.8 [1.01-9.26]; P = 0.047). Gender, phenotype, and early development of gait instability, aid-requiring ambulation, orthostatic symptoms, neurogenic bladder, or significant anhidrosis (thermoregulatory sweat test ≥ 40%) were not indicators of shorter survival. Our data suggest that early development of severe generalized autonomic failure more than triples the risk of shorter survival in patients with MSA.

Autonomic testing of women with interstitial cystitis/bladder pain syndrome.

PurposeInterstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by urinary urgency, frequency, nocturia, pain worse as the bladder fills and improved after emptying. These features might suggest abnormal autonomic bladder control mechanisms. We compared the structural integrity of the autonomic nervous system (ANS) in IC/BPS and control subjects.MethodsIRB-approved study at University Hospitals Case Medical Center, Cleveland, OH to evaluate the structural integrity of the ANS in adult females. Testing included cardiovascular response to deep breathing, Valsalva maneuver, 30 min head up tilt, and sudomotor test.ResultsDifferences in ANS integrity for IC/BPS subjects and controls were determined by modified Composite Autonomic Severity Score (CASS) that includes sudomotor, adrenergic and cardiovascular indices. Baseline heart rate (HR) and HRs from each of three 10 min upright segments of a tilt test were compared and trend analyses performed using t tests. Healthy and IC/BPS subjects were demographically similar. The two groups did not differ in modified-CASS scores but elevated average peak heart rate was evident during baseline (supine; p = 0.057) for IC/BPS subjects prior to a tilt test. Difference at baseline was maintained at each interval during the tilt, with nearly identical slopes across intervals. The preliminary nature of this report denotes a small sample size and important differences may not be detected.ConclusionsThe findings show no structural ANS abnormalities in IC/BPS subjects. Higher baseline HR supports the concept of functional rather than structural change in the ANS, such as abnormality of sympathetic/parasympathetic balance that will require further evaluation.

Small nerve fiber involvement is frequent in X-linked adrenoleukodystrophy

To investigate the presence of small nerve fiber dysfunction in subjects with X-linked adrenoleukodystrophy. Cross-sectional study in which 11 Norwegian subjects (3 males, 8 females) with X-linked adrenoleukodystrophy, phenotypes ranging from asymptomatic to wheelchair-bound with adrenomyeloneuropathy, were investigated with neurophysiologic studies including EMG, nerve conduction velocities, quantitative sensory testing, tests of autonomic function, and skin biopsy for intraepidermal nerve fiber density measurements. We found small nerve fiber dysfunction in 10 of 11 subjects, increasing with age and more pronounced in males. Low intraepidermal nerve fiber densities were found in 5 of 11 subjects, indicating a loss of thin unmyelinated nerve fibers peripherally. Five of 11 subjects showed small nerve fiber dysfunction despite normal nerve fiber densities, suggesting possible involvement of the spinothalamic tracts. Two subjects showed moderate abnormalities in autonomic function tests. Evidence of small nerve fiber dysfunction was widespread in this cohort of subjects with X-linked adrenoleukodystrophy, with findings indicating loss of peripheral small nerve fibers and possibly also fibers of the spinothalamic tracts. The results support the theory of primary axonal degeneration in adrenomyeloneuropathy. Evidence of nervous system involvement was found in all heterozygotes, with severity increasing with age. Clinicians caring for these patients should be alert to signs of small nerve fiber involvement.

Higher heart rate increments on head-up tilt in control subjects are not associated with autonomic dysfunction

ObjectiveTo determine whether there is altered autonomic function associated with elevated heart rate increments on head-up tilt (HUT) in younger individuals. MethodsA total of 149 subjects were enrolled in this study. Subjects underwent the autonomic reflex screen including HUT and completed the Autonomic Symptom Profile. ResultsHeart rate increment on HUT did not show a correlation with Composite Autonomic Severity Score (CASS) and the individual CASS scores were low (score 0/10, n=103; score 1/10, n=27; score 2/10, n=1; score 3/10, n=2). There was no correlation with multiple autonomic domains assessed by the Autonomic Symptom Profile. However, there were significant inverse correlations between heart rate increment and total COMPASS score including male sexual dysfunction (r=−0.318; p=0.011; n=64), bladder (r=−0.209; p=0.014; n=138), pupillomotor (r=−0.235; p=0.006; n=138) and male sexual dysfunction (r=−0.554; p<0.0001; n=64). These domains showed a positive correlation with age and a significant effect of age but not heart rate increment with regression analysis (except pupillomotor domain). ConclusionsThese results argue against a reduction in autonomic function underlying the higher heart rate increments seen on HUT in younger individuals. SignificanceThese findings argue that the development of Postural Tachycardia Syndrome involves mechanisms that potentially occur independently of heart rate increment.

Spectrum of autonomic dysfunction in orthostatic dizziness

ObjectiveTo investigate the frequency and detailed spectrum of autonomic dysfunction in patients with orthostatic dizziness (OD). MethodsOver 20months, 217 consecutive patients with OD as a presenting symptom of orthostatic intolerance were enrolled. The distribution and severity of autonomic dysfunction were measured by the composite autonomic severity score (CASS), which was derived from a standard autonomic function test including Finapres for recording of the beat-to-beat blood pressure. Sympathetic indexes (SIs) were calculated from the Valsalva maneuver (VM). ResultsApproximately 83% of patients showed at least one abnormal autonomic testing result. We classified OD into 11 groups according to the patterns of autonomic dysfunctions. The most common pattern was generalized autonomic failure of sympathetic adrenergic and parasympathetic cardiovagal functions (n=60). Patients with delayed OH had larger BP increases during late phase II of the VM (p=0.04), showed greater phase IV overshoot (p=0.04), and had a smaller pressure recovery time increase (p=0.02) than patients with classic OH. Each SI showed the strongest correlation with the CASS adrenergic subscores. ConclusionsOD can present with a board spectrum of autonomic dysfunctions. SignificanceThis investigation could be useful in understanding the pattern and mechanism of autonomic dysfunction associated with OD.

Autonomic Neuropathy in HIV is Unrecognized and Associated with Medical Morbidity

Autonomic dysfunction is common in HIV. However, its clinical impact is not well understood and its protean symptoms make it difficult to diagnose. We sought to determine: (1) whether autonomic neuropathy is associated with morbidity and predicted mortality in HIV as measured by the Veterans Aging Cohort Study (VACS) index; and (2) if healthcare providers recognize the diagnosis of autonomic neuropathy. Data were obtained from 102 HIV-infected adults enrolled in a prevalence study of autonomic dysfunction from 2011-2012. Participants were predominantly minority with nearly equal numbers of men and women. Most were receiving an antiretroviral regimen with a nucleoside reverse transcriptase inhibitor backbone and a base of a non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor. Autonomic neuropathy was defined using a laboratory-based autonomic assessment, the Composite Autonomic Severity Score (CASS). Medical records were reviewed for the year prior to the autonomic assessment. We found that the autonomic neuropathy score (CASS) was associated with the VACS index. We also found that among 53 participants with symptomatic autonomic neuropathy, the diagnosis had been considered for only one. The majority of the symptoms were either unexplained or attributed to medication side effects. This study demonstrates that autonomic neuropathy in HIV is associated with serious co-morbid illnesses known to increase mortality risk, and that HIV healthcare providers rarely consider autonomic neuropathy in their differential diagnoses. Future studies are needed to determine if autonomic neuropathy is an independent risk factor for mortality in HIV, and to raise awareness of its signs and symptoms.

Rates of autonomic dysfunction in HIV patients receiving antiretroviral therapy

We read the work by Robinson-Papp et al. with interest. The authors report that 61 % of participants had autonomic dysfunction (AD) as defined by a composite autonomic severity score (CASS) >3, with peripheral nerve dysfunction being the strongest predictor, affecting 90 % of participants who have HIV-associated distal symmetric polyneuropathy. Eighty-six percent of individuals with AD were symptomatic on survey of autonomic symptoms (SAS). The Composite Autonomic Scoring Scale (CASS) is a validated scale designed to quantify autonomic failure. CASS is derived from three areas of autonomic function: adrenergic, cardiovagal, and sudomotor (1996; Weimer 2010; Low et al. 2008). A CASS of 6 is indicative of severe autonomic failure (Low et al. 2008). CASS has been correlated with cardiovascular disease events and mortality (Gehrking et al. 2013). A CASS of 4–6 has been associated with orthostatic hypotension, abnormal sweating, and gastrointestinal abnormalities and is usually seen in autonomic failure (Low 1993). The authors report a median CASS of 3, suggesting that 50 % of subjects had a CASS of >3. The study reported on the CASS upper range of 6. A CASS this high would implicate major clinical outcomes and mortality which frankly have not been seen in large epidemiologic studies. The rates and severity of AD may have been overestimated in this study. In a convenience sample of 48 virologically suppressed HIV-infected individuals with and without polyneuropathy, we reported on a median CASS of 1 (IQR 1), and 40 % of subjects were symptomatic. We utilized the Composite Autonomic Symptom Scale to measure autonomic symptoms, a better instrument to detect and quantitate AD compared to the SAS used in the study. We wonder whether using the Q-sweat test for evaluating the sudomotor response used in the study may have overestimated AD. The qualitative sudomotor axon reflex test (QSART) has been a routine postganglionic sudomotor function test of the Mayo Clinic since 1983. The Q-sweat test is a commercial quantitative sweat measurement test modeled on QSART, but can overestimate sudomotor dysfunction (Sletten et al. 2010). In the era of combination antiretroviral therapy (cART), dramatic improvements in morbidity and mortality have been witnessed. However, autonomic symptoms such as light-headedness, dry mouth and eyes, cold feet, and constipation, as noted in the study and ours, have become common complaints among HIV-infected patients. AD has been correlated with HIV disease progression (Becker et al. 1997; Chow et al. 2011). Individuals with AIDS receiving cART have better measures of autonomic function compared to individuals that are not on cART (Correia et al. 2006). Forty-two percent of the study participants had a detectable viral load. Early and lifelong suppression of HIV infection and avoidance of medications that cause peripheral neuropathy and metabolic disorders needs to be considered for HIV-infected individuals (Askgaard et al. 2011). AD is a common condition. The rate and severity of autonomic dysfunction may not appear as elevated as suggested by the authors. Nonetheless, we commend Robinson-Papp et al. for bringing attention to AD which we agree is an underappreciated condition that is becoming increasingly common among our aging HIV-infected patients. Further investigation is needed to explain the prevalence and nature of AD, and its potential treatment.

Dynamic pupillometry as an autonomic testing tool

To determine normal values for pupillometry indices in healthy control subjects and to examine these indices in patients with autonomic dysfunction and healthy controls. Infrared video pupillometry was used to investigate the pupil response to a brief light flash in 79 healthy controls, 28 patients with normal autonomic function (composite autonomic severity score, CASS<2), and 26 patients with moderate to severe autonomic failure (CASS>4) seen in our autonomic laboratory from January 2008 to June 2011. In six subjects, we examined the effects of varying light stimulus intensity and light stimulus duration. Descriptive analysis, correlation, and ANCOVA adjusted for age were performed. We determined eight indices corresponding to parasympathetic and sympathetic pupil function. Baseline pupil diameter (BPD), maximum constriction velocity (MCV), absolute constriction amplitude (ACA), and maximum dilation velocity (MDV) negatively correlated with age (p<0.01) among controls. MCV and ACA increased with increasing intensity of light stimulus from 3.5 to 112μW. Indices of parasympathetic pupil innervation (MCV and ACA) were lower in the high CASS group compared to others (p<0.0001). Indices of sympathetic pupil function, time to reach 75% of initial resting diameter during pupillary dilation (T¾), and dilation velocity at T¾ (DV¾) did not differ significantly in the three study groups. However, T¾ corrected for the magnitude of pupillary constriction (T¾:ACA) was higher in the high CASS group suggesting sympathetic dysfunction in that group (p=0.0003). Indices of pupillomotor function significantly differ between patients with moderate to severe autonomic failure and healthy controls.

Autonomic dysfunction is common in HIV and associated with distal symmetric polyneuropathy

Neurologic complications of HIV are well characterized in the central and peripheral nervous systems but not in the autonomic nervous system, perhaps due to the complexities of measuring autonomic function in medically ill populations. We hypothesized that autonomic dysfunction is common in HIV, can be meaningfully measured with an autonomic reflex screen, and is associated with distal symmetric polyneuropathy (DSP) but not with signs of CNS disease. We also sought to characterize immunovirologic and medical factors associated with autonomic dysfunction. We assessed 102 HIV-infected adults for autonomic dysfunction with a laboratory-based autonomic reflex screen summarized as the composite autonomic severity score (CASS). The total neuropathy score (TNS) was used to quantify DSP based on neurologic interview/examination, quantitative sensory testing, and nerve conduction studies. Autonomic dysfunction was common, with a CASS ≥ 3 in 61 % of participants, of whom 86 % were symptomatic. Greater CASS abnormalities demonstrated univariate association with increasing TNS, age, viral load, hypertension, and use of medications (particularly anticholinergics), but not with antiretrovirals, current/nadir CD(4+) count, HIV duration, metabolic factors, or signs of CNS disease. The TNS was the only significant predictor of the CASS in multivariate analysis; anticholinergic medications were marginally significant. This study demonstrates that autonomic dysfunction is common and frequently symptomatic in HIV and that an autonomic reflex screen, adjusted for anticholinergic medication, is useful in its assessment. Association of autonomic dysfunction with DSP suggests common factors in their pathogenesis, and autonomic neuropathy may be part of the spectrum of HIV-associated peripheral nerve pathologies.

Cholinergic Autonomic Dysfunction in Veterans With Gulf War Illness

The authors of prior small studies raised the hypothesis that symptoms in veterans of the 1991 Gulf War, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction, are due to cholinergic autonomic dysfunction. To perform a confirmatory test of this prestated hypothesis in a larger, representative sample of Gulf War veterans. Nested case-control study. Clinical and Translational Research Center, University of Texas Southwestern Medical Center, Dallas. Representative samples of Gulf War veterans meeting a validated case definition of Gulf War illness with 3 variants (called syndromes 1-3) and a control group, all selected randomly from the US Military Health Survey. Validated domain scales from the Autonomic Symptom Profile questionnaire, the Composite Autonomic Severity Score, and high-frequency heart rate variability from a 24-hour electrocardiogram. The Autonomic Symptom Profile scales were significantly elevated in all 3 syndrome groups (P< .001), primarily due to elevation of the orthostatic intolerance, secretomotor, upper gastrointestinal dysmotility, sleep dysfunction, urinary, and autonomic diarrhea symptom domains. The Composite Autonomic Severity Score was also higher in the 3 syndrome groups (P= .045), especially in syndrome 2, primarily due to a significant reduction in sudomotor function as measured by the Quantitative Sudomotor Axon Reflex Test, most significantly in the foot; the score was intermediate in the ankle and upper leg and was nonsignificant in the arm, indicating a peripheral nerve length-related deficit. The normal increase in high-frequency heart rate variability at night was absent or blunted in all 3 syndrome groups (P< .001). Autonomic symptoms are associated with objective, predominantly cholinergic autonomic deficits in the population of Gulf War veterans.

Autonomic dysfunction in patients with orthostatic dizziness: Validation of orthostatic grading scale and comparison of Valsalva maneuver and head-up tilt testing results

ObjectivesTo investigate whether the Korean version of the Orthostatic Grading Scale (KOGS) is a reliable and valid measure for evaluating the severity of symptoms of orthostatic intolerance (OI) and to compare the diagnostic accuracy of Valsalva maneuver (VM) and head-up tilt test (HUTT) in identifying sympathetic adrenergic failure (SF). MethodsA back-translation approach was used to develop the KOGS. One hundred seventy two patients with orthostatic dizziness (OD) as a presenting symptom of OI and 133 healthy controls were enrolled. All patients completed the 5-item, self-report KOGS and 58% (100/172) of patients were randomly selected for a retest with the questionnaire. The degree of the severity of autonomic dysfunction was measured by the composite autonomic severity score (CASS). ResultsThe incidence of orthostatic hypotension (OH) in HUTT was 21%. The KOGS scores in patients showed good internal consistency (Cronbach's α=0.90) and test-retest reliability (correlation coefficient=0.77 to 0.89). The total and each item scores of KOGS correlated with the degree of the severity of autonomic dysfunction estimated as CASSs in patients. Approximately 70% (116/172) of patients showed at least one abnormality in either HUTT or VM. The incidence (43%) of an abnormal BP response in VM was two times higher than the incidence of OH in HUTT. DiscussionThe KOGS is a reliable and valid tool for screening patients with OD. VM is superior to HUTT in detecting SF. Thus, VM and HUTT should be combined to evaluate adrenergic sympathetic function in patients with OD.

A Prospective, 1-Year Follow-up Study of Postural Tachycardia Syndrome

ObjectiveTo prospectively evaluate patients who met standard criteria for postural tachycardia syndrome (POTS), at baseline and 1-year follow-up, using standard clinical and laboratory methods to assess autonomic function. MethodsFifty-eight patients met the study criteria (orthostatic symptoms and a heart rate increment of ≥30 beats/min on head-up tilt) and completed 12 months of follow-up. All patients were enrolled and completed the study from January 16, 2006, through April 15, 2009. Patients underwent standardized autonomic testing, including head-up tilt, clinical assessment, and validated questionnaires designed to determine the severity of autonomic symptoms. ResultsPatients were predominantly young females (n=49, 84%), with 20 patients (34%) reporting an antecedent viral infection before onset of symptoms. More than one-third (37%) no longer fulfilled tilt criteria for POTS on follow-up, although heart rate increment on head-up tilt did not differ significantly at 1 year (33.8±15.1 beats/min) compared with baseline (37.8±14.6 beats/min) for the entire cohort. Orthostatic symptoms improved in most patients. Autonomic dysfunction was mild as defined by a Composite Autonomic Severity Score of 3 or less in 55 patients (95%) at baseline and 48 patients (92%) at 1 year. ConclusionTo our knowledge, this is the first prospective study of the clinical outcomes of patients with POTS. Orthostatic symptoms improved in our patients, with more than one-third of patients no longer fulfilling tilt criteria for POTS, although the overall group change in heart rate increment was modest. Our data are in keeping with a relatively favorable prognosis in most patients with POTS.

Small Fiber Sensory Neuropathy in Parkinson Disease with Autonomic Failure (P06.056)

Objective: To answer the question whether a small fiber neuropathy (SFN) in Parkinson disease (PD) is restricted to autonomic fibers or it represents more widespread degenerative process that also affects sensory small fibers. Background There is large evidence about damage of the autonomic small fibers but there is limited knowledge about involvement of sensory small fibers in PD. Design/Methods: 55 PD patients with symptomatic autonomic failure (PD-AF) were subjected to quantitative autonomic testing (AT). Sensory SFN was tested using skin biopsies for determination of epidermal nerve fiber density (ENFD). AT included deep breathing, Valsalva maneuver, tilt and quantitative axon sudomotor test. Three mm punch biopsies were done at proximal thigh and distal leg sites. Severity of parkinsonism was evaluated by the UPDRS. Severity of dysautonomia was evaluated using Composite Autonomic Severity Score (CASS). Results: CASSs were: 5.4+-2.2 total, 1.6+-1.1 cardiovagal, 2.2+-1.3 adrenergic and 1.7+-1.0 sudomotor. Abnormal CASSs were obtained in 100% of subjects (cardiovagal in 80%, adrenergic in 95% and sudomotor in 86%). Mild GAF was detected in 23%, moderate in 38% and severe in 29% of subjects. Reduced ENFD consistent with sensory SFN was detected overall in 44 subjects (80%); in 7(54%) subjects with mild GAF, in 13 (62%) with moderate GAF and in 12 (75%) subjects with severe GAF. There were significant correlations between total and adrenergic CASS and UPDRS. ENFD at distal leg correlated with sudomotor volumes at foot, with UPDRS and with CASS (total and adrenergic). Conclusions: Sensory SFN is common in PD-AF. The severity of sensory SFN correlates both with severity of parkinsonism and severity of dysautonomia. Sensory SFN is probably a part of more generalized SFN that affects both sensory and autonomic fibers. Autonomic involvement may precede sensory involvement. Proper recognition of sign of SFN can lead to more optimal treatment of autonomic and sensory symptoms in PD. Disclosure: Dr. Novak has nothing to disclose. Dr. Ravin has received research support from Kyowa, Juvantia-Santhera, Acadia Pharmaceuticals. Dr. Qin has nothing to disclose.

Evaluation of Dermal Myelinated Fibers in Diabetic Polyneuropathy (IN1-1.002)

Objective: We hypothesize that patients with diabetic polyneuropathy (DPN) will have evidence of demyelination in dermal myelinated fibers compared to healthy controls. Background Glabrous skin is enriched with myelinated fibers due to vertically oriented intrapapillary myelinated fiber endings (IME) to mechanoreceptors, the most common being Meissner corpuscles (MC). Therefore, biopsy of glabrous skin affords a minimally invasive method to investigate myelinated nerves. Design/Methods: Eight diabetic patients (3 with type 1, 5 with type 2) and six healthy age matched controls with mean age 55 vs. 51 were evaluated with clinical examination, the Michigan Diabetic Neuropathy Score (MDNS), nerve conduction studies (NCS), autonomic testing, and the Michigan Neuropathy Screening Instrument (MNSI). Immunohistochemistry was performed on 2 and 3 mm skin punches from the lateral index finger and distal leg, respectively. Results were analyzed with Kruskal Wallis or Wilcoxan Rank Sum test. Results: Peroneal motor conduction velocity, amplitude, composite autonomic severity score, MDNS and MNSI were significantly different in diabetic patients (p=0.04 to Conclusions: In conclusion, abnormalities in dermal myelinated fibers and mechanoreceptors are observed in DPN patients compared to controls. Further studies of dermal myelinated fibers may be helpful in elucidating the mechanism of demyelination in DPN. Supported by: NINDS K23 NS056009 to A.C. P., NINDS R01 R01NS066927-01 to J.L., Vanderbilt Diabetic Research Training Center, and Vanderbilt CTSA grant 1 UL1 RR024975. Disclosure: Dr. Myers has nothing to disclose. Dr. Li has nothing to disclose. Dr. Artibee has nothing to disclose. Dr. Peltier has nothing to disclose.

Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy

Autonomic deficits in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have not been adequately quantitated. The Composite Autonomic Severity Score (CASS) is a validated instrument for laboratory quantitation of autonomic failure derived from standard autonomic reflex tests. We characterized dysautonomia in CIDP using CASS. Autonomic function was retrospectively analyzed in 47 patients meeting CIDP criteria. CASS ranges from 0 (normal) to 10 (pandysautonomia), reflecting summation of sudomotor (0-3), cardiovagal (0-3), and adrenergic (0-4) subscores. Severity of neurologic deficits was measured with Neuropathy Impairment Score (NIS). Degree of small fiber involvement was assessed with quantitative sensation testing. Thermoregulatory sweat test (TST) was available in 8 patients. Patients (25 men) were middle-aged (45.0 ± 14.9 years) with longstanding CIDP (3.5 ± 4.3 years) of moderate severity (NIS, 46.5 ± 32.7). Autonomic symptoms were uncommon, mainly gastrointestinal (9/47; 19%) and genitourinary (8/47; 17%). Autonomic deficits (CASS ≥1) were frequent (22/47; 47%) but very mild (CASS, 0.8 ± 0.9; CASS ≤3, all cases). Deficits were predominantly sudomotor (16/47; 34%) and cardiovagal (10/47; 21%) with relative adrenergic sparing (4/47; 9%). TST was abnormal in 5 of 8 patients (anhidrosis range, 2%-59%). Sudomotor impairment was predominantly distal and postganglionic. Somatic deficits (disease duration, severity, small fiber deficits) did not predict presence of autonomic deficits. Our data characterize the autonomic involvement in classic CIDP as mild, cholinergic, and predominantly sudomotor mainly as a result of lesions at the distal postganglionic axon. Extensive or severe autonomic involvement (CASS ≥4) in suspected CIDP should raise concern for an alternative diagnosis.

Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests

BackgroundMultiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterised by autonomic failure, manifested as orthostatic hypotension or urogenital dysfunction, with combinations of parkinsonism that is poorly responsive to...

Detection of small‐fiber neuropathy by sudomotor testing

The symptoms of burning sensation affecting the feet, thought to be due to a distal small-fiber neuropathy (DSFN) affecting somatic unmyelinated fibers, are usually accompanied by vasomotor or sudomotor changes suggestive of involvement of autonomic fibers. We therefore examined the relationship between pattern of anhidrosis and DSFN and its etiology, comparing patients with "pure" DSFN (with normal nerve conduction) to those with clinical DSFN (minor conduction abnormalities). We reviewed 125 cases with a clinical phenotype of DSFN. These patients had distal burning discomfort, variable sensory deficits, and intact motor function. All had undergone assessment with thermoregulatory sweat test (TST), autonomic reflex screen (ARS), and nerve conduction studies and electromyography (NCS/EMG). TST showed a distal pattern of anhidrosis in 74%. The quantitative sudomotor axon reflex test (QSART) was abnormal in 74%, with 80% of those having a length-dependent pattern of anhidrosis/hypohidrosis. In total, 93% of patients had a distal pattern of abnormality on QSART or TST. The Composite Autonomic Severity Score (CASS) was used to quantify the severity and distribution of autonomic deficits: 98% had CASS abnormality (sudomotor, 98%; adrenergic, 43%; cardiovagal, 35%). EMG was normal or showed unrelated abnormalities in 75%. The most common etiologies of DSFN were idiopathic (73%), presumed hereditary (18%), and diabetes (10%). Sudomotor examination is thus a highly sensitive detection tool in DSFN. Autonomic involvement is mainly distal, and additionally may involve adrenergic and the long cardiovagal fibers.