Composite autonomic severity scoring in spinocerebellar ataxia type 1 and 2.

OBJECTIVES: The aim of the present study was to evaluate the integrity of autonomic nervous system in spinocerebellar ataxia (SCA) type 1 and 2 patients using battery of autonomic function tests and their comprehensive scoring using composite autonomic severity score (CASS). MATERIAL AND METHODS: Battery of autonomic function test comprising of cardiovascular (baroreflex dependent and non-baroreflex dependent) and sudomotor functions were assessed in age and gender-matched SCA1 (n = 31), SCA2 (n = 40) patients along with healthy controls (n = 40). To assess the grade of autonomic abnormalities, the composite autonomic severity score (CASS) was computed using the results of the standard autonomic function tests. RESULTS: We found reduction in baroreflex dependent autonomic reactivity parameters predominantly a significant fall of systolic blood pressure (<0.001) and lower 30:15 ratio (<0.001) during head up tilt in both the SCA1 and SCA2 as compared to controls. On sudomotor assessment, distal leg latency of sweat response was prolonged in SCA1 than SCA2 patients. Moderate generalized autonomic failure was commonly found amongst SCA1 (80.65%) and SCA2 (85%) patients. Severe autonomic failure was found to be more in SCA1 (6.45%) than SCA2 (2.50%) patients. CONCLUSIONS: Cardiovascular autonomic function assessment in SCA1 and SCA2 patients revealed a significant impairment in the baroreflex loop integrity. Severity scoring using CASS suggests the existence of moderate autonomic failure in majority of both SCA1 and SCA2 patients.

Differential role of central and peripheral arterial stiffness in determining brachial artery resting retrograde flow in patients with ischemic heart disease vs healthy subjects.

Retrograde flow in endothelial cell cultures has been shown to induce a pro-atherogenic phenotype. Despite its potential role as a pathophysiological link between cardiovascular risk factors and atherosclerotic disease, resting retrograde flows between patients with cardiovascular disease and healthy subjects have not been compared. Further, the vascular characteristics governing retrograde flow in human arteries have not been systematically investigated. Association of central and peripheral vascular characteristics with retrograde flow profile was investigated in 32 healthy subjects and 47 patients with ischemic heart disease. Endothelial dysfunction was assessed by brachial ultrasound-based calculation of flow-mediated dilation (FMD) and sub-clinical atherosclerosis was estimated from carotid-intima media thickness (CIMT). Retrograde blood flow velocity (RBFV) and shear rate were comparable between the two groups (RBFV 1.82(0.97-3.32) vs 1.78(1.24-2.65) cm/s p = 0.79). Augmentation index was a significant determinant of retrograde flow in both patients and healthy subjects. Carotid artery incremental elastic modulus was an independent determinant of retrograde flow patterns in healthy subjects while ejection fraction, cf/cr PWV ratio and forearm vascular conductance emerged as independent determinants in patients. Retrograde flow patterns were also associated with FMD (RBFV r = -0.43, p = 0.004) and CIMT (r = 0.30, p = 0.041) in patients. The results of the study suggest a difference in the determinants of retrograde flow in patients and healthy subjects, with central arterial stiffness being a major contributor in healthy subjects while interaction between central, peripheral, and cardio-arterial factors influence retrograde flow in patients with ischemic heart disease.

Respiratory Dysfunction in Parkinson's Disease: Relation with Dysautonomia.

Background: Parkinson's disease (PD) is a neurodegenerative disease perceived as a motor disorder. It is most commonly associated with autonomic dysfunction, affecting multiple systems. This altered autonomic control might be reflected by a parallel change in the airway caliber of these patients. Aim: To correlate the pulmonary impairment in patients with Parkinson's disease with the underlying dysautonomia. Materials and Methods: A total of 30 patients with Parkinson's disease participated in the study. Heart rate (HR) variability was recorded for 5 min to assess the autonomic dysfunction, followed by impulse oscillometry (IOS) and spirometry. IOS being an effort independent technique uses sound waves at different frequencies (5-25 Hz) to measure the airway impedance. Results: There was a significant decrease in SDSD (6.60 (10.18-6.01) vs. 12.22 (13.95-11.30); P = 0.04), RMSSD (6.59 (10.17-5.50) vs. 12.20 (13.93-11.28); P = 0.04), and total power (315.8 (506.3-120.7) vs. 771.3 (799.0-643.6); P = 0.04) in stage II as compared to stage I. Resistance at 20 Hz (R20) was found to be positively correlated with SDSD (r = 0.40, P = 0.04), RMSSD (r = 0.40, P = 0.04), and HF (r = 0.41, P = 0.03). Conclusion: Amongst the PD population, any changes in the parasympathetic component (responsible for bronchoconstriction) due to the underlying dysautonomia might be reflected as increased airway resistance in the pulmonary system.

Cortical and Subcortical Brain Area Atrophy in SCA1 and SCA2 Patients in India: The Structural MRI Underpinnings and Correlative Insight Among the Atrophy and Disease Attributes.

INTRODUCTION: Genetically defined spinocerebellar ataxia (SCA) type 1 and 2 patients have differential clinical profile along with probable distinctive cortical and subcortical neurodegeneration. We compared the degree of brain atrophy in the two subtypes with their phenotypic and genotypic parameters. METHODS: MRI was performed using a 3T scanner (Philips, Achieva) to obtain 3D T1-weighted scans of the whole brain and analyzed by FreeSurfer (version 5.3 and 6 dev.) software. Genetically proven SCA1 (n = 18) and SCA2 (n = 25) patients with age-matched healthy controls (n = 8) were recruited. Clinical severity was assessed by the International Cooperative Ataxia Rating Scale (ICARS). To know the differential pattern of atrophy, the groups were compared using ANOVA/Kruskal-Wallis test and followed by correlation analysis with multiple corrections. Further, machine learning-based classification of SCA subtypes was carried out. RESULT: We found (i) bilateral frontal, parietal, temporal, and occipital atrophy in SCA1 and SCA2 patients; (ii) reduced volume of cerebellum, regions of brain stem, basal ganglia along with the certain subcortical areas such as hippocampus, amygdala, thalamus, diencephalon, and corpus callosum in SCA1 and SCA2 subtypes; (iii) higher subcortical atrophy SCA2 than SCA1 (iv) correlation between brain atrophy and disease attributes; (v) differential predictive pattern of two SCA subtypes using machine learning approach. CONCLUSION: The present study suggests that SCA1 and SCA2 do not differ in cortical thinning while a characteristic pattern of subcortical atrophy SCA2 > SCA1 is observed along with correlation of brain atrophy and disease attributes. This may provide the diagnostic guidance of MRI to SCA subtypes and differential therapies.

Structural atrophy of central autonomic network correlates with the functional attributes of autonomic nervous system in spinocerebellar ataxia patients.

OBJECTIVE: Spinocerebellar ataxia (SCA) is a neurodegenerative disorder in which, autonomic dysfunction is a common manifestation. Brain area atrophy also involves the areas comprising central autonomic network (CAN) in SCA. Structural atrophy of CAN and autonomic dysfunction should go hand in hand. But this important relationship has not been studied to date. Therefore, using SCA as a disease model, the present study has been designed to explore the plausible correlations between the brain areas of CAN and clinical autonomic function modalities in SCA patients. MATERIALS AND METHODS: 3D T1-weighted scans were acquired on 3T MRI, analyzed by FreeSurfer software in genetically confirmed forty-nine SCA patients (SCA1 = 18, SCA2 = 25 and SCA3 = 6). Heart rate variability (HRV), blood pressure variability (BPV), baroreflex sensitivity (BRS), and autonomic reactivity tests were used for evaluation of autonomic nervous system. Additionally, autonomic dysfunction scoring was done using composite autonomic severity score (CASS). RESULTS: On correlation analysis, the study showed the association of atrophic cortical and subcortical brain areas (predominantly prefrontal cortex, bilateral middle temporal, left cuneus, left lingual and left caudate) with altered clinical autonomic function parameters in SCA patients. These areas were primarily comprised of sympathetic and parasympathetic brain areas of CAN. One of the key brain areas of CAN - left cuneus was found to be associated with both HRV (r = 0.295, p = 0.040) and BRS (r = 0.326, p = 0.022). CONCLUSION: A characteristic pattern of association between particular brain areas of CAN and clinical autonomic function parameters was observed in SCA patients.

Brachial Artery "Low-Flow Mediated Constriction" Is Associated with Myocardial Perfusion Defect Severity and Mediated by an Altered Flow Pattern during Occlusion.

INTRODUCTION: The relationship between low flow-mediated constriction (LFMC), a new proposed measure of endothelial function, with cardiovascular disease severity and its hypothesized stimulus, that is, low flow, has not been comprehensively evaluated. The study evaluated association between change in brachial artery diameter during constriction with severity of myocardial perfusion defect (PD) and alterations in different components of flow profile. METHODS: Brachial artery responses to occlusion were assessed in 91 patients and 30 healthy subjects. Change in anterograde and retrograde blood flow velocities (delta anterograde blood flow velocity and retrograde blood flow velocity), anterograde shear rate and retrograde shear rate (delta ASR and RSR, respectively), and oscillatory shear index (delta) during forearm occlusion at 50 mm Hg above systolic pressure, from baseline was calculated. Myocardial perfusion was evaluated in patients using exercise single positron emission computed tomography and % myocardial PD was calculated from summed stress score. RESULTS: LFMC emerged as independent predictor of defect severity after correcting for age and gender (p = 0.014). Sixty-seven patients (73.6%) and 15 healthy subjects (50%) showed constriction during occlusion. In stepwise backward regression analysis, RSR contributed 35.5% and ASR contributed 20.1% of the total 63.9% variability in artery diameter during occlusion. CONCLUSION: The results suggest that LFMC is independently associated with myocardial perfusion severity and is "mediated" by an altered flow profile during occlusion.

Autonomic Tone and Baroreflex Sensitivity during 70° Head-up Tilt in Yoga Practitioners.

INTRODUCTION: The intervention of yoga was shown to improve the autonomic conditioning in humans evident from the enhancement of parasympathetic activity and baroreflex sensitivity (BRS). From the documented health benefits of yoga, we hypothesized that the experience of yoga may result in adaptation to the orthostatic stress due to enhanced BRS. AIM: To decipher the effects of yoga in the modulation of autonomic function during orthostatic challenge. MATERIALS AND METHODS: This was a comparative study design conducted in autonomic function test lab, of the Department of Physiology, All India Institute of Medical Sciences, New Delhi, India. Heart rate variability (HRV), blood pressure variability, and BRS were analyzed on forty naïve to yoga (NY) subjects and forty yoga practitioners with an average age of 31.08 ± 7.31 years and 29.93 ± 7.57 years, respectively. All participants were healthy. Seventy degrees head up tilt (HUT) was used as an intervention to evaluate the cardiovascular variability during orthostatic challenge. RESULTS: During HUT, the R-R interval (P = 0.042), root mean square of succesive R-R interval differences (RMSSD) (P = 0.039), standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) (P = 0.039) of HRV, and sequence BRS (P = 0.017) and α low frequency of spectral BRS (P = 0.002) were higher in the yoga group. The delta decrease in RRI (P = 0.033) and BRS (P < 0.01) was higher in the yoga group than the NY group. CONCLUSION: The efferent vagal activity and BRS were higher in yoga practitioners. The delta change (decrease) in parasympathetic activity and BRS was higher, with relatively stable systolic blood pressure indicating an adaptive response to orthostatic challenge by the yoga practitioners compared to the NY group.

The Low-Flow-Mediated Arterial Constriction in the Upper Limbs of Healthy Human Subjects are Artery Specific and Handedness Independent.

Low-flow-mediated constriction (LFMC) has been used to assess resting endothelial function in peripheral conduit arteries. The literature describes discrepancies in the behaviour of radial versus brachial artery in response to low-flow state, the reasons for which were not addressed in a systematic and scientific way. Moreover, the influence of handedness on observed LFMC responses has not been investigated. The present study aimed at systematic measurement and comparison of the LFMC responses in radial and brachial arteries of both dominant and non-dominant arms of healthy human volunteers. We also investigated the physiological factors associated with differential LFMC response of radial versus brachial artery in the same group of subjects. Longitudinal B mode ultrasonographic cine loops of radial and brachial arteries were acquired at baseline and after producing distal circulatory arrest. Cine loops were screen grabbed and analyzed later using automated edge detection algorithms to measure end-diastolic diameters. Distal circulatory arrest was produced over the proximal forearm (for the brachial artery) and over the wrist (for the radial artery) at 250 mm Hg for 5 min after baseline measurements. Results suggested that arterial location (p = 0.0001) and baseline diameter (p < 0.0021) emerged as independent predictors of LFMC response. Differences in the LFMC responses are handedness independent and could be attributed to the arterial location along with the differences in their baseline diameters.

Depressed baroreflex sensitivity from spontaneous oscillations of heart rate and blood pressure in SCA1 and SCA2.

OBJECTIVES: To assess the time and frequency domain measures of cardiac autonomic activity/tone in patients of genetically defined spinocerebellar ataxia (SCA) types 1 and 2, as well as to decipher the probable associations among the cardiovascular autonomic parameters and genetic and clinical characteristics. MATERIALS AND METHODS: Simultaneous 5-min recording of RR interval (RRI) and blood pressure (BP) for the calculation of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were performed in genotypically confirmed SCA1 (n = 31) and SCA2 (n = 40) patients and healthy controls (n = 40). Additionally, the International Cooperative Ataxia Rating Scale (ICARS) was used for scoring of clinical severity in SCA patients. RESULTS: Time and frequency domain parameters of HRV, BPV and BRS were depressed in SCA1 and SCA2 subtypes as compared to controls, although there was no statistically significant difference in autonomic tone between the two SCA subtypes. On correlation analysis, autonomic tone parameters were found to be associated with the clinical and genetic features of the SCA subtypes. Also, ICARS was associated with the genotype (CAG repeat length) in SCA2 patents. CONCLUSIONS: Cardiac autonomic tone is depressed in both SCA1 and 2 as compared to healthy controls while the two SCA subtypes do not differ in terms of autonomic tone. Also, a typical association exists between disease characteristics and autonomic indices.

Diabetic status and grade of nonalcoholic fatty liver disease are associated with lower baroreceptor sensitivity in patients with nonalcoholic fatty liver disease.

OBJECTIVES: Baroreceptor sensitivity (BRS), a functional consequence of vascular stiffness, may be affected by the presence of diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). The present study was designed to assess the effect of diabetic status and NAFLD grade on the BRS in patients with NAFLD. METHODS: Seventy-five individuals (25 NAFLD without DM, 25 NAFLD with DM and 25 controls) were recruited for the study who underwent anthropometric and body composition analysis along with estimation of plasma glucose, serum insulin and serum lipids. BRS and blood pressure variability (BPV) analysis was carried out in both time and frequency domains. Carotid-radial and carotid-dorsalis pedis artery pulse wave velocity, and radial artery augmentation index were computed as measures of arterial stiffness. RESULTS: BRS was found to be lower in the NAFLD with DM group as well those with grade II NAFLD compared with the controls. Correlation analysis showed a negative correlation of BRS with postprandial blood glucose level (r=-0.39) and BMI (r=-0.467). The diabetic status and grade of NAFLD were associated independently with a decrease in BRS as well as the low-frequency component of diastolic BPV. The augmentation index and carotid-distal pulse wave velocity were higher in the NAFLD with DM group compared with controls. CONCLUSION: Both the diabetic status and grade of NAFLD were shown to have an independent effect on the decrease in the BRS with a consequent effect on BPV, with a greater influence of diabetic status rather than NAFLD grade on arterial stiffness.

Comparison of Autonomic Function before and after Surgical Intervention in Patients with Temporal Lobe Epilepsy.

BACKGROUND AND PURPOSE: Refractory temporal lobe epilepsy (TLE) is commonly associated with imbalances in cardiovascular (CV) parasympathetic and sympathetic functions, which are treated using TLE surgery. We investigated the effect of hemispheric lateralization of seizure foci on autonomic CV functions before and after TLE surgery. METHODS: The study was conducted on patients with left TLE (LTLE, n = 23) and right TLE (RTLE, n = 30) undergoing unilateral TLE surgery. To assess the autonomic CV functions, changes in the heart rate (ΔHR) and blood pressure (BP) were measured using a standardized battery of autonomic reactivity tests before surgery and at 3 and 6 months after surgery. RESULTS: Before surgery, ΔHR and the expiration to inspiration ratio (E:I) during the deep breathing test were higher in the LTLE group than in the RTLE group (both p < 0.001), but both outcomes were comparable between the groups at 3 and 6 months. ΔHR decreased at 3 and 6 months (p < 0.001 and 0.01, respectively) compared with preoperative values. The E:I at 3 months in the LTLE group was lower (p = 0.04) than the preoperative values. Decrease in systolic BP during the head-up tilt test was greater in the LTLE group than in the RTLE group (p = 0.002) before surgery. The maximum increase in diastolic BP during the cold pressor test was lower in the RTLE group at 6 months than that before surgery (p = 0.001) and in the LTLE group (p = 0.002). CONCLUSIONS: We found that hemispheric lateralization of seizure foci in the temporal lobe had a differential effect on autonomic CV functions before surgery. Before surgery, parasympathetic reactivity was higher in the LTLE group, and sympathetic reactivity was higher in the RTLE group. After surgery, autonomic CV functions were comparable between the groups, suggesting that TLE surgery stabilizes autonomic CV functions.

A Novel Practical to Demonstrate Systemic and Local Regulation of Circulation in a Human Subject.

Purpose of the study: Systemic and local regulation of peripheral circulation is a vital concept to be taught to undergraduate medical students. There is lack of an effective practical module to demonstrate and reinforce the theoretical understanding of this concept. Methodology: We designed a simple feasible novel practical using finger pulse recording coupled with hand grip test and reactive hyperemia protocol to elicit systemic and local regulation of peripheral circulation respectively. Main findings: The reduction in finger pulse amplitude during hand grip contralateral to the exercising hand demonstrates systemic regulation while the isolated ipsilateral increase in finger pulse amplitude during reactive hyperemia demonstrates local regulation. Conclusion: : Here we propose a simple novel practical for effective demonstration of systemic and local regulation of circulation for under-graduate teaching in physiology.

Vascular Responses to Post Occlusive Reactive Hyperemia and Systemic Inflammation in Overlap Syndrome of Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea.

BACKGROUND: Post-occlusive reactive hyperemia (RH) is impaired in Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA). The aim of the present study was to examine systemic vascular response and endothelial function in patients of Overlap Syndrome (OS) of COPD and OSA and also to investigate whether OS has any additional effect on endothelial dysfunction when compared to dysfunction caused by COPD alone. METHODS: 31 COPD patients and 13 healthy controls participated in the study. Overnight Polysomnogra was done to classify the patients into COPD only group (Apnea-Hypopnea Index <5) (n=15) and OS group (AHI >5) (n=16). Peripheral pulse waveform changes during reactive hyperemia were assessed using digital Photoplethysmography (PPG) technique in which pulse wave amplitude (PWA), Maximum slope of upstroke and Pulse Transit Time (PTT) were measured. C - reactive protein was assessed as marker of inflammation by ELISA. RESULTS: Maximum percentage changes in PWA during RH were significantly lower in the both COPD group [20.34(12.02-34.07)] (p<0.001) and Overlap Syndrome group [10.96(6.21-21.49)] (p<0.0001) as compared to Controls [49.79(46.03-65.32)], whereas amplitude responses were not significantly different in the COPD and OS group (p>0.05). Maximum percentage change in slope of upstroke showed similar responses in the three groups. CRP levels (mg/) were raised in COPD [11.60(1.75-15.00] (p<0.001) and OS group [12.52(5.28- 15.70))](p<0.0001) as compared to controls [0.59(0.58-0.91)]. Maximum percentage change in amplitude negatively correlated with serum CRP levels in COPD group (r=-0.557, p=0.03) and in OS group (r=-O.552, p= 0.02). FEV1% predicted positively correlated with maximum percentage change in amplitude in OS group(r=0.579, p=0.018). No correlation of AHI was found with any of the vascular function parameter in Overlap group. CONCLUSION: The patients with Overlap Syndrome have systemic inflammation and impaired reactive hyperaemia response. However, no additive effect of OSA was observed on impaired RH in patients with co-existing COPD.

L-glutamate microinjection in the preoptic area increases brain and body temperature in freely moving rats.

The role of the preoptic area (POA) in thermoregulation is well documented. Microinjection of various neurotransmitters into the POA in rats has been shown to influence body temperature. Alhough there are reports showing changes in temperature on administration of L-glutamate into the POA, the role of this excitatory amino acid in thermoregulation has not been studied in unanaesthetized rats. In the present study, brain and body temperatures were recorded in freely moving adult male Wistar rats with K-type thermocouple implanted near the hypothalamus and temperature transmitter implanted inside the peritoneum. Recordings were performed 2 h preinjection and 4 h postinjection. L-glutamate (0.14 nM) microinjection into the POA induced long-lasting hyperthermia and reduced locomotor activity. The rats remained curled up and showed piloerection. L-glutamate-induced hyperthermia was attenuated by previous injection of the ionotropic L-glutamate receptor antagonist, kynurenate (0.11 nM). We propose that L-glutamate in the POA participates not only in heat production and conservation but also plays a role in interlinking sleep and thermoregulation.

Monitoring of reactive hyperemia using photoplethysmographic pulse amplitude and transit time.

BACKGROUND: Peripheral arterial tonometry and Ultrasound measurement of flow mediated dilation have been the widely reported noninvasive techniques to assess vasodilation during reactive hyperemia (RH). OBJECTIVE: Simultaneous monitoring of dilatation and tone of the vasculature during RH induced by venous occlusion (VO) and arterial occlusion (AO) has been presently attempted using simple noninvasive measures of photoplethysmography (PPG). METHODS: Finger-PPG characteristics that include pulse timings, amplitude, upstroke-slope and pulse transit time (PTT) were studied before (1 min), post-VO (5 min) and post-AO (5 min) in 11 healthy volunteers. RESULTS: PPG amplitude was significantly increased to maximum at 2nd min of post-AO (1.28 +/- 0.11 vs. 1.0 nu, P<0.05) as compared to the baseline; meanwhile, no significant changes (P>0.05) in PPG amplitude was observed during post-VO. Tremendous increase in PTT was evident at 1st min of post- AO (196.6 +/- 3.3 vs. 185.3 +/- 3.6 ms, P<0.0001) and was maintained significantly longer through 1-5 min of post-AO. Relatively small but significant increase in PTT was noticed only at 1st min of post-VO (193.9 +/- 6.8 vs. 189.6 +/- 6.2 ms, P<0.0001), followed by an immediate recovery to baseline by 2nd min of post-VO. The increase in PTT (i.e. DeltaPTT) was higher at 1st min of post-AO (11.4 +/- 1.3 vs. 4.3 +/- 1.1 ms) as compared to post-VO. CONCLUSION: Results suggests that PTT response reflects the myogenic components in the early part of RH and PPG amplitude response reflects the metabolic component reinforcing the later course of RH. PPG amplitude and PTT can be used to quantify the changes in diameter and tone of the vessel wall, respectively during RH. The collective responses of PPG amplitude and PTT can be more appropriate to facilitate PPG technique for monitoring of vasodilation caused by RH.

Monitoring of cardiovascular reactivity to cold stress using digital volume pulse characteristics in health and diabetes.

OBJECTIVE: Cold pressor test (CPT) assesses sympathetic reactivity by the rise in diastolic blood pressure secondary to the vasoconstriction during immersion of hand in cold water. Presently, monitoring of vascular reactivity in health and diabetes during CPT has been attempted by objective measures of Photoplethysmogram (PPG) that include amplitude, upstroke-slope, pulse timings and pulse transit time (PTT). METHODS: Finger-PPG characteristics were studied before and during CPT (1 min) in 11 healthy volunteers and 10 diagnosed Type 2 Diabetes Mellitus (DM) patients. In controls, the recordings were continued for 5 min after CPT. RESULTS: The amplitude of PPG significantly decreased due to cold stress in both control and DM groups (P < 0.0001 and P < 0.003, respectively). However, the decrease in amplitude was significantly lesser (0.42 +/- 0.08 nu vs. 0.25 +/- 0.03 nu, P = 0.04) in DM group than controls. The slope response of PPG resembled the amplitude. PTT was significantly shortened in control and DM groups (180.0 +/- 3.8 ms vs. 187.1 +/- 3.9 ms, P < 0.006, 177.7 +/- 7.0 ms vs. 192.9 +/- 5.6 ms, P = 0.002, respectively) during CPT as compared to baseline. However, the decrease in PTT was significantly higher (-15.2 +/- 3.4 ms vs. -6.0 +/- 1.9 ms, P = 0.03) in DM patients than controls. No significant differences were noticed in Delta changes of peak-to-peak interval, crest time and decay time of PPG between the two groups. CONCLUSION: This preliminary study suggests that the collective responses of PPG amplitude and PTT can be used to objectively quantify the sympathetic reactivity to cold stress in health as well as to detect the deficits of vascular reactivity in diabetes. Further studies would substantiate the simple PPG technique in quantifying the neuronal and vascular dysfunction.