Reduced cardiac <Superscript>123</Superscript>I-MIBG uptake reflects cardiac sympathetic dysfunction in de novo Parkinson’s disease

It remains unclear whether cardiac iodine-123-labeled metaiodobenzylguanidine (¹²³I-MIBG) uptake is clinically related to autonomic dysfunction on conventional autonomic function testing in de novo Parkinson’s disease (PD). We therefore studied the relation between cardiac ¹²³I-MIBG uptake and cardiovascular autonomic dysfunction in patients with de novo PD. The subjects were 26 patients with de novo PD. The ratio of the average pixel count in the heart to that in the mediastinum was calculated to derive the cardiac ¹²³I-MIBG uptake. Cardiovascular autonomic function was evaluated on the basis of cardiovascular autonomic response on the Valsalva maneuver (VM), and systolic blood pressure response (SBP) on head-up tilt-table testing (HUT). Patients with de novo PD had significantly reduced cardiac ¹²³I-MIBG uptake as compared with controls (1.58 ± 0.43 vs. 2.25 ± 0.34, p = 0.0001) and cardiovascular autonomic response on the VM. No significant difference in the fall in SBP on HUT was found between patients with de novo PD and the controls. Cardiac ¹²³I-MIBG uptake in de novo PD was not significantly related to vasomotor sympathetic function, baroreceptor reflex gain, cardiac parasympathetic function, or the changes in SBP on HUT. Cardiac ¹²³I-MIBG uptake was, however, significantly related to the blood pressure overshoot in phase IV of the VM (r = 0.648, p = 0.0003). Cardiac ¹²³I-MIBG uptake began to decrease in association with the reduction in the overshoot of phase IV on the VM. Cardiac ¹²³I-MIBG uptake clinically reflects cardiac sympathetic dysfunction in de novo PD.     

Cardiovascular autonomic dysfunction in dementia with Lewy bodies and Parkinson's disease

OBJECTIVE: We estimated the extent and pattern of cardiovascular autonomic dysfunction in dementia with Lewy bodies (DLB) as compared with that in Parkinson's disease (PD). METHODS: We performed meta-iodobenzylguanidine ((123)I-MIBG) scintigraphy of the heart and hemodynamic autonomic function testing using the Valsalva maneuver in 27 patients with DLB, 46 with PD, and 20 controls. RESULTS: (123)I-MIBG uptakes in DLB were reduced as compared with those in control and PD. Hemodynamic studies revealed that DLB had decreased baroreceptor reflex and reduced responses of SBP in phases II and IV as compared with PD and control. SBP responses on standing and the difference in plasma norepinephrine (NE) concentrations between supine and standing positions were reduced in PD as compared with those in control. Furthermore, SBP responses on standing, plasma NE concentrations in supine and standing positions, and the difference in plasma NE concentrations between these positions were significantly lower in DLB than in PD and control. Plasma NE concentrations in DLB with orthostatic hypotension (OH) were lower than that in DLB without OH, although some patients who had DLB with orthostatic hypotension had relatively normal plasma NE levels. CONCLUSION: Cardiovascular autonomic dysfunction is more severe in DLB than in PD and is usually caused by the loss of postganglionic sympathetic nervous function, although dysautonomia in some patients with DLB may result from preganglionic dysfunction.     

Cardiac parasympathetic dysfunction concurrent with cardiac sympathetic denervation in Parkinson's disease

We aimed to characterize the relationship between cardiac sympathetic and parasympathetic dysfunction employing cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake and other autonomic function parameters in Parkinson's disease (PD). 79 PD patients were studied. We performed (123)I-MIBG myocardial scintigraphy to assess the extent of cardiac sympathetic denervation. Electrocardiogram readings at rest and postural change in blood pressure were also examined. Coefficient variation of RR intervals (CVR-R) was used as an index for cardiac parasympathetic activity. Cardiac (123)I-MIBG uptake did not vary significantly among the Hoehn-Yahr (H-Y) stages. There was a significant correlation between cardiac (123)I-MIBG uptake and CVR-R (early, r=0.457, p<0.001; late, r=0.442, p<0.001). While the correlation was present among the patients who had had the disease less than two years (early, r=0.558, p<0.001; late, r=0.530, p<0.001), the patients with the disease duration longer than two years did not have such a significant correlation. Age, disease duration, corrected QT interval, or postural blood pressure change did not correlate with cardiac (123)I-MIBG uptake. Orthostatic hypotension was observed in 13 out of 72 subjects, and reduced CVR-R was a major determinant for the development of orthostatic hypotension. We conclude that cardiac parasympathetic dysfunction occurs concurrent with sympathetic denervation as revealed by (123)I-MIBG myocardial scintigraphy in PD and contributes to the development of orthostatic hypotension.     

Association of visual hallucinations with reduction of MIBG cardiac uptake in Parkinson's disease

BACKGROUND: Postganglionic cardiac sympathetic denervation is evident in patients with Parkinson's disease (PD) and iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy has proven to be a useful tool for diagnosis of PD. OBJECTIVE: To elucidate the factors associated with severity of cardiac sympathetic nerve dysfunction in PD patients. METHODS: We investigated 95 PD patients hospitalized in the Department of Neurology at Tottori University Hospital. (123)I-MIBG cardiac scintigraphy was performed on each patient and the early and delayed heart to mediastinum (H/M) ratios and washout rate (WR) of (123)I-MIBG cardiac scintigraphy were calculated. Independent predictive variables for parameters of (123)I-MIBG cardiac scintigraphy were analyzed by multivariate regression analysis. RESULTS: Multivariate regression analysis revealed that the presence of visual hallucinations (VH) and the patient's age at the time of evaluation independently predicted the early or delayed H/M ratio. Analysis of covariance, adjusted for the age of the patients as covariates, revealed that the early and delayed H/M ratios of PD patients with VH but no dementia, as well as PD patients with dementia were significantly lower than the ratios in PD patients with no VH or dementia. CONCLUSION: Cardiac sympathetic dysfunction may be associated with the presence of VH in PD patients.     

Olfactory dysfunction and cardiovascular dysautonomia in Parkinson’s disease

Several studies have reported that olfactory dysfunction is an early neuropathological manifestation of Parkinson’s disease (PD). Reduced cardiac meta-iodobenzylguanidine (¹²³I-MIBG) uptake may be one of the earliest signs of PD. We studied the relation of olfactory dysfunction to cardiovascular dysautonomia in patients with PD. The study group comprised 66 patients with PD (70.5 years) and 26 controls (70.3 years) for olfactory assessment, 21 controls (72.1 years) for cardiac ¹²³I-MIBG scintigraphy and heart rate variability (HRV), assessed using the coefficient of variation for RR intervals (HRV), and 23 controls (69.2 years) for orthostatic blood pressure response. Olfactory function was assessed by the odor stick identification test Japan (OSIT-J), and cardiovascular autonomic function was evaluated by ¹²³I-MIBG scintigraphy of the heart, the fall in orthostatic blood pressure, and HRV. Patients with PD had a significantly lower OSIT-J score than did the controls (4.1 ± 3.0 vs. 9.9 ± 1.7, p = 0.001). The OSIT-J score was unrelated to variables other than gender, including age, disease duration, motor score on the unified Parkinson’s disease rating scale, score on the mini-mental state examination, motor phenotype, visual hallucinations, and dopaminergic medication on multiple regression and logistic regression analyses. The OSIT-J score was related to the heart/mediastinum ratio of cardiac ¹²³I-MIBG uptake, the fall in orthostatic blood pressure, and HRV, after adjustment for other clinical variables. Olfactory dysfunction in PD was, thus, significantly related to both cardiac sympathetic and parasympathetic dysfunction, as well as vascular sympathetic dysfunction. As non-motor symptoms of PD, olfactory dysfunction and autonomic network failure appear to be closely related in PD.     

Cardiac sympathetic dysfunction in Parkinson's disease--relationship between results of 123I-MIBG scintigraphy and autonomic nervous function evaluated by the Valsalva maneuver]

We examined whether the results of 123I-MIBG scintigraphy reflect cardiac sympathetic nerve function in patients with Parkinson's disease (PD). The subjects were 62 patients with Parkinson's disease (age, 65.4 +/- 6.3 years) and 53 controls (65.2 +/- 7.1 years). All subjects underwent 123I-MIBG scintigraphy and QTc interval measurement on ECG. Hemodynamic autonomic function was estimated by the Valsalva maneuver in 37 subjects (63.9 +/- 5.2 years) randomly selected from the patients with PD. As control, the Valsalva maneuver was also done in 20 randomly selected controls (64.1 +/- 5.0 years), and 123I-MIBG scintigraphy was performed in 21 controls (67.7 +/- 5.3 years old). The subjects rested in a supine position for 20 min and were given an intravenous injection of 111 MBq 123I-MIBG. Relative organ uptake was determined by the region of interest (ROI) in the anterior view and the ratio of average pixel count in the heart (H) to that in the mediastinum (M) was calculated (H/M ratio) for early (after 15 min) and delayed (after 3 hrs) periods. The Valsalva maneuver was done by having the subjects exhale into a mouthpiece at an expiratory pressure of 40 mmHg for 15 seconds. Blood pressure and RR intervals were measured during the Valsalva maneuver by tonometry, using a noninvasive blood pressure monitoring system (ANS 508, Nihon Colin Co., Ltd.). Baroreceptor reflex sensitivities (BRS) of the second phase (BRS II) and fourth phase (BRS IV) of the Valsalva maneuver were calculated, and blood pressure elevations during the late second phase (IIp) and fourth phase (IVp) were measured. QTc was greater in the patients with PD (417 ms) than in the control subjects (409 ms). The H/M ratios of the early and delayed images in the patients with PD (1.76, 1.61) were significantly lower than those in the control subjects (2.56, 2.45). The early and delayed H/M ratios significantly correlated with the severity of disease according to Hoehn-Yahr stage. QTc interval and IVp significantly correlated with early and delayed H/M ratios. No other significant correlations were detected. The early H/M ratio in the patients with PD who had IVp within the normal range was lower than the early H/M ratio in control subjects. Our results show that early and delayed H/M ratio correlates with cardiac autonomic function, evaluated on the basis of QTc interval and the Valsalva maneuver, but not with baroreceptor reflex sensitivity or vasomotor autonomic function. Our findings suggest that silent cardiac autonomic dysfunction may be evaluated by 123I-MIBG scintigraphy, because early and delayed H/M ratios were lower in the patients with PD who had normal IVp than in the control subjects.     

Cardiac MIBG scintigraphy is a sensitive tool for detecting cardiac sympathetic denervation in Parkinson's disease.

[(123)I]Metaiodobenzylguanidine ([(123)I]MIBG) cardiac scintigraphy could be helpful to differentiate Parkinson's disease (PD) from multiple system atrophy (MSA), demonstrating that, in PD with autonomic failure but not in MSA, there is a myocardial postganglionic sympathetic dysfunction. To investigate whether this method is more sensitive than standard autonomic testing to detect early involvement of sympathetic cardiac efferent, we analyse MIBG myocardial uptake in 8 PD patients with normal autonomic testing (nondysautonomia PD group, NDPD) in comparison with 10 PD patients with abnormal autonomic testing (dysautonomia PD group, DPD) and 10 MSA patients. Global MIBG uptake was assessed using the ratio of [(123)I]MIBG uptake in the heart to the upper mediastinum (H/M) on planar scintigraphic data. Regional MIBG uptake was determined on two single photon emission tomography scans in regions of the left ventricle. The mean H/M ratios were significantly different among the three groups (P < 0.0001). H/M ratios of both NDPD and DPD patients groups (H/M = 1.83 +/- 0.50 and 1.24 +/- 0.40, respectively) were significantly lower than in MSA patients (H/M = 2.52 +/- 0.60). However, in NDPD patients, H/M was significantly higher than in DPD patients. When compared to MSA patients, NDPD patients showed a regional reduction in MIBG uptake in all left ventricle regions markedly in the apex and the inferior wall. Our results suggest that MIBG myocardial scintigraphy (analysis of both H/M ratio and regional MIBG uptake) may be more sensitive than standard autonomic testing for the early detection of silent autonomic dysfunction in PD.     

Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson's disease

BACKGROUND: Iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy has been used to evaluate cardiac sympathetic denervation in Lewy body disease (LBD) including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Patients with LBD had marked reductions in cardiac MIBG accumulation, indicative of severe impairment of the cardiac sympathetic nervous systems. However, the differences in scintigraphy between DLB and PD have not been determined. OBJECTIVE: To compare cardiac sympathetic function in early disease stage measured with 123I-MIBG scintigraphy between DLB and PD. METHODS: 123I-MIBG myocardial scintigraphy was performed in 22 patients with early-stage DLB, 41 patients with early idiopathic PD and 15 normal control subjects who were matched for age and disease duration. The heart-to-mediastinum (H/M) ratio was calculated. RESULTS: 123I-MIBG uptake of the myocardium was significantly lower in patients with early DLB than in controls. The mean value of H/M ratio in patients with DLB was significantly lower than those in patients with PD, independent of the Hoehn and Yahr stage. CONCLUSIONS: Our findings suggest that cardiac sympathetic function in DLB is severely impaired even in the early disease stage.     

Cardiac denervation occurs independent of orthostatic hypotension and impaired heart rate variability in Parkinson's disease

Patients with idiopathic Parkinson's disease (PD) have impaired sympathetically mediated neurocirculatory innervation. Here we analyzed the correlation between cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, orthostatic hypotension and heart rate variability in treated patients with PD. Orthostatic hypotension (OH) as a hallmark of sympathetic neurocirculatory failure was found with a high prevalence in PD. PD is known to affect cardiac innervation, resulting in a suppressed heart rate variability and a postganglionic noradrenergic lesion. We measured continuous arterial blood pressure in rest and 70 degrees head-up tilt for at least 20 min, heart rate variability in the supine position, standing, deep respiration and Valsalva manoeuvre in 58 patients with PD (27 male, 31 female; mean age 71 years, mean PD duration 5.1 years, Hoehn and Yahr 3.1+/-0.8). Sympathovagal balance was estimated by the low-frequency (LF: 0.04-0.15Hz) and high-frequency bands (HF: 0.15-0.4Hz) ratio in the analysis of heart rate variability in each condition. Myocardial adrenergic function was analyzed by imaging MIBG using the single-photon emission computed tomography technique. MIBG uptake expressed as heart-to-mediastinum ratio was reduced in all PD patients (H/M-ratio: 1.14+/-0.16). We found no correlation between myocardial MIBG uptake and sympathovagal balance, blood pressure or other autonomic findings. The LF/HF ratio in tilt-table testing was significantly more reduced in PD with OH than without OH (2.18 vs. 1.49, p=0.022). MIBG uptake did not differ. It is concluded that scintigraphy with MIBG appears to be a highly sensitive and useful tool to demonstrate sympathetic postganglionic cardiac nerve disturbances. Loss of sympathetic innervation of the heart seems to occur early and independent of orthostatic hypotension, baroreflex failure and impaired heart rate variability in PD.     

Cardiac 123I-MIBG scintigraphy in patients with essential tremor.

In some cases, it is difficult to differentiate essential tremor (ET) from Parkinson's disease (PD), especially in the early stages of the disease. We investigated cardiac sympathetic dysfunction using (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 22 patients with ET, in comparison with early PD and tremor-dominant PD (TDPD). The mean ratio of (123)I-MIBG uptake in the region of interest in the heart to that in the mediastinum (H/M ratio) was significantly greater in patients with ET (1.99 +/- 0.21) than in those with either TDPD (1.28 +/- 0.11) or early PD (1.28 +/- 0.17; each P < 0.001). The H/M ratio in all patients with ET was greater than two standard deviations above the range of the ratio in the patients with early PD or TDPD.     

Valsalva manoeuvre in patients with different Parkinsonian disorders

The valsalva manoeuvre (VM), used as an autonomic function test, can detect sympathetic and/or parasympathetic autonomic dysfunction. This study investigated the value of VM in patients with different Parkinsonian syndromes (PS). We continuously recorded blood pressure, ECG and respiration among 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson’s disease (PD) and in 27 healthy subjects matched in age and sex (Con). VM was performed in addition to metronomic breathing and tilt-table testing. VM could not be analysed in 26% of the ES patients. Valsalva ratio (VR), as a parameter of cardiovagal function, was pathologically decreased in all patient groups. Valsalva ratio (VR) was not able to discriminate parasympathetic dysfunction between patients and controls as well as E/I ratio of metronomic breathing. As a parameter of sympathetic dysfunction during VM, the physiological increase of blood pressure was more often missing during phase IV than phase II especially in PD and MSA patients. Correlation with orthostatic hypotension during tilt-table testing was only moderate. Although VM can demonstrate sympathetic and parasympathetic autonomic dysfunction, we cannot recommend VM as a first line autonomic test in PS patients. Metronomic breathing and tilt-table test seem more capable as parasympathetic resp. and sympathetic function tests to identify cardiovascular abnormalities in PS patients.     

Cardiovascular dysautonomia in de novo Parkinson’s disease without orthostatic hypotension

Background: Clinical symptoms of Parkinson’s disease (PD) include not only motor distress, but also autonomic dysfunction. Objective: To study the characteristics of subclinical autonomic nervous dysfunction in de novo PD without orthostatic hypotension (OH). Methods: Autonomic nervous function including cardiac sympathetic gain was evaluated on the basis of cardiac radioiodinated metaiodobenzylguanidine (MIBG) uptake, the response to the Valsalva maneuver, and spectral analyses of the RR interval and blood pressure in 20 patients with de novo PD without OH. Results: Decreased cardiac MIBG uptake was found even in patients with PD without OH. Hemodynamic studies using the Valsalva maneuver revealed that patients with PD without OH had preserved baroreceptor reflex sensitivity in phase II and phase IV. Blood pressures normally responded in early and late phase II, but not in phase IV. Blood pressure recovery time was slightly reduced in patients with PD without OH when compared with the value in controls. The low frequency component of the RR interval and systolic blood pressure and the ratio of RR‐LF to RR‐HF in de novo PD without OH were significantly reduced when compared with the control values, whereas the high frequency component of the RR interval did not differ significantly. Conclusion: These results show that latent cardiac and vasomotor sympathetic dysfunction but not parasympathetic dysfunction is already present in early stage de novo PD, even without orthostatic hypotension.     

Beat-to-beat blood pressure analysis after premature ventricular contraction indicates sensitive baroreceptor dysfunction in Parkinson's disease.

Extrasystoles occur in normal subjects but are significant more frequently (16.25% vs. 55%; chi(2) = 19.3; P < 0.001) seen in Parkinson's disease (PD) patients. The extrasystolic decreases in stroke volume and systolic pressure activate sympathetic vasomotor innervation and lead to a blood pressure increase for a few heartbeats. The purpose of this study was to prove whether the short time analysis of this blood pressure regulation allows the assessment of sympathetic neurocirculatory function. Records of noninvasive blood pressure monitoring were reviewed from 40 PD patients and 80 controls. A battery of cardiovascular autonomic tests, including Valsalva maneuver, tilt-table testing, echocardiography, and cardiac scintigraphy with [(123)I]meta-iodobenzylguanidine were performed. Fifty-five percent of the PD patients had at least one premature ventricular contraction (PVC) in 10 minutes lying supine at rest. After every PVC (13 PVCs) recorded from normal subjects, we found an increase in systolic blood pressure above base line with a maximum at the seventh heart beat. In all of the 22 PD patients, the systolic blood pressure was significantly decreased less than baseline in every PVC from the second to the ninth postextrasystolic beat (P < 0.001). In both groups, the extrasystolic fall in blood pressure was on average approximately 22%. The postextrasystolic potentiation did not differ (5.3% vs. 4.4%, not significant). If a PVC occurs, the analysis of short-time blood pressure regulation is a sensitive tool for baroreceptor reflex function. The advantage of this method results from the independence of patients cooperation and the high sensitivity to prove a sympathetic neurocirculatory failure within 10 heart beats.     

Measurement of myocardial accumulation of123I-metaiodobenzylguanidine for studying cardiac autonomic neuropathy in diabetes mellitus

The association of myocardial¹²³I-metaiodobenzylguanidine (MIBG) accumulation and autonomic neuropathy, as well as factors known to affect autonomic nervous function, were studied in a group of 12 diabetic patients representing different degrees of autonomic failure. The early myocardial uptake phase of¹²³I-MIBG was measured by calculating the peak net influx rate for the first 30 min after the¹²³I-MIBG injection and by single photon emission computed tomography (SPECT) imaging 1 h after the injection. The retainment of¹²³I-MIBG in the myocardium was measured using SPECT imaging 6 h after the injection, and myocardial uptake and the myocardium/liver uptake ratio were calculated. The 6-h myocardium/liver uptake ratio of¹²³I-MIBG was significantly (p<0.05) lower in the diabetic patients with clinically evident autonomic neuropathy compared with those without autonomic neuropathy. Geater body mass index was associated with lower peak net influx rate and 1-h myocardial uptake of¹²³I-MIBG, and greater diastolic blood pressure was associated with lower 1-h myocardial uptake of¹²³I-MIBG, whether or not the patients had diabetic autonomic neuropathy. In conclusion, reduction in the 6-h myocardium/liver uptake ratio of¹²³I-MIBG is related to diabetic autonomic neuropathy. Because the early¹²³I-MIBG accumulation in myocardium is reduced in diabetic patients with greater body mass index and diastolic blood pressure, irrespective of autonomic neuropathy, our results encourage the use of the late myocardial accumulation of¹²³I-MIBG for studying sympathetic neuropathy in the diabetic heart.     

123I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson's disease

OBJECTIVES: (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is clinically used to estimate local myocardial sympathetic nerve damage in some forms of heart disease, autonomic nerve disturbance in diabetic neuropathy, and disturbance of the autonomic nervous system in neurodegenerative disease. In the present study, examinations were performed to clarify (1) the proportion of cardiac sympathetic nerve disturbance in Parkinson's disease, (2) the usefulness of (123)I-MIBG myocardial scintigraphy to detect sympathetic nerve disturbances compared with autonomic function tests, (3) cardiac function in patients who have a decreased MIBG uptake in (123)I-MIBG myocardial scintigraphy, (4) the usefulness of (123)I-MIBG myocardial scintigraphy to differentiate Parkinson's disease from the other neurological diseases mimicking it. METHODS: (123)I-MIBG myocardial scintigraphy was performed, together with autonomic function tests and cardiac examinations in 46 patients with Parkinson's disease and 25 patients with vascular parkinsonism, essential tremor, or multiple system atrophy. RESULTS: In an anterior image study, the average count per pixel in heart to mediastinum (H/M) ratio decreased in 80% of the patients with Parkinson's disease in the early phase and 84% in the late phase. The mean H/M ratio in Parkinson's disease was significantly lower than that in controls and the other diseases. The H/M ratio tended to decrease with the disease progression. In almost half of the patients in Hoehn and Yahr stage I, the H/M ratio was already decreased. The sympathetic skin response in upper and lower limbs, head up tilt test, and coefficient of variation of R-R interval were abnormal in 17%, 31%, 30%, and 17% of the patients, respectively. All the patients with abnormal autonomic functions were in Hoehn and Yahr stage III, IV, or V. Echocardiography showed normal left ventricular function. Twenty four hour Holter electrocardiography detected no serious arrhythmias except for one patient with non-sustained ventricular tachycardia. CONCLUSION: (123)I-MIBG myocardial scintigraphy might detect early disturbances of the sympathetic nervous system in Parkinson's disease and might give useful diagnostic information to differentiate vascular parkinsonism, essential tremor, and multiple system atrophy from Parkinson's disease.     

Cardiovascular dysautonomia in Parkinson's disease and multiple system atrophy

OBJECTIVES: To determine whether Parkinson's disease (PD) can be distinguished from multiple system atrophy (MSA) on the basis of the assessment of iodine-123 meta-iodobenzylguanidine (123I-MIBG) radioactivity in heart and cardiovascular autonomic function. PATIENTS AND METHODS: Seventeen patients with MSA, 39 with PD, and 25 healthy volunteers underwent 123I-MIBG scintigraphy and hemodynamic autonomic function tests using Valsalva maneuver (VM). Baroreceptor reflex sensitivity (BRS) was measured using the slope of the relation between RR interval and blood pressure during the fourth phase. RESULTS: 123I-MIBG radioactivity in heart of patients with PD was lower than that of control subjects and patients with MSA, but there was some overlap between PD and MSA. BRS in patients with PD who had a 123I-MIBG radioactivity similar to that in MSA was larger than that in patients with MSA, with no overlap in any patient. CONCLUSION: Assessment of BRS may be useful for differentiating between MSA and PD that had a 123I-MIBG radioactivity similar to MSA.     

Relationship between cardiac 123I-metaiodobenzylguanidine scintigraphy and cardiovascular autonomic function test (standing test) in Parkinson's disease]

We investigated the correlation between results of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy and those of cardiovascular autonomic function tests in patients with Parkinson's disease (PD). 123I-MIBG myocardial scintigraphy and a 5-minute standing test were performed in 50 patients with PD and in 19 control subjects. The value of the basal plasma noradrenaline (NA) level was used as an index of basal sympathetic nerve activity, and %NA was used to assess the response of sympathetic nerve activity. In addition, the parameters of DeltaBP and DeltaHR were evaluated to assess the autonomic response of the cardiovascular system. A mild, but significant correlation was observed between the myocardium to mediastinum (H/M) ratio and the values of the plasma NA baseline (r = 0.35, p < 0.05 in early image, r = 0.29, p < 0.05 in delay image). No significant correlation was observed between the H/M ratio and the other parameters (%NA, DeltaBP, DeltaHR). These results suggest that 123I-MIBG myocardial scintigraphy may be associated with the basal sympathetic nerve activity, but not with autonomic nervous response of the cardiovascular system in patients with PD.     

Cardiac parasympathetic dysfunction in the early phase of Parkinson’s disease

Cardiac parasympathetic function is strongly affected by aging. Although sympathetic dysfunction has been well documented in Parkinson’s disease (PD), cardiac parasympathetic dysfunction has not been well studied. The objective of this study was to clarify the development of cardiac parasympathetic dysfunction in the early phase of PD and to explore the age-corrected correlation between cardiac parasympathetic dysfunction and cardiac sympathetic dysfunction. We reviewed 25 healthy controls and 56 patients with idiopathic PD of Hoehn and Yahr stages I–III. We evaluated cardiac parasympathetic function using the Valsalva ratio, the baroreflex sensitivity (BRS) and the coefficient of variation of RR intervals in the resting state (resting-CVRR) and during deep breathing (DB-CVRR). In addition, we measured cardiac ¹²³I-metaiodobenzylguanidine (MIBG) uptake to investigate the relationship between cardiac sympathetic and parasympathetic dysfunction in PD. Compared with healthy controls, patients with PD showed significantly decreased cardiac parasympathetic parameters (resting-CVRR 2.8 ± 1.3 vs. 1.7 ± 0.6%, p < 0.001; DB-CVRR 5.8 ± 2.3 vs. 3.8 ± 1.7%, p < 0.001; Valsalva ratio 1.52 ± 0.26 vs. 1.34 ± 0.17, p < 0.01; BRS 10.6 ± 9.5 vs. 5.0 ± 5.4 ms/mmHg, p < 0.01). In particular, resting-CVRR and DB-CVRR were significantly decreased in the early phase of PD. In age-corrected analyses, none of the parasympathetic indices correlated with the delayed cardiac ¹²³I-MIBG uptake. These observations indicate that cardiac parasympathetic dysfunction occurs in the early phase of PD, but not necessarily in parallel with cardiac sympathetic dysfunction.     

Serum heart-fatty acid binding protein levels in patients with Lewy body disease

OBJECTIVE: In order to examine a possible role of serum heart-fatty acid binding protein (H-FABP) in patients with Lewy body disease, we measured serum levels of H-FABP in patients with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD). METHODS: Serum levels of H-FABP were measured using a solid-phase enzyme-linked immunoassay. Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy was performed on each patient and the heart to mediastinum (H/M) ratio was calculated. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the H-FABP between DLB and AD patients. Independent predictive variables for serum H-FABP levels were analyzed using multivariate regression analysis. RESULTS: Serum levels of H-FABP were significantly higher in DLB patients and PD patients than in AD patients. H/M ratios of the DLB and PD patients were significantly lower than those of AD patients. The diagnostic value of the serum H-FABP levels between AD and DLB patients was inferior to that of the delayed H/M ratio of (123)I-MIBG cardiac scintigraphy. Multivariate regression analysis revealed that the delayed H/M ratio predicted serum H-FABP levels in the PD patients. CONCLUSIONS: Examination of serum H-FABP levels did not allow discrimination between DLB and AD patients. Cardiac sympathetic nerve dysfunction may be associated with elevation of serum H-FABP in Lewy body disease patients.     

Cardiovascular dysautonomia in de novo Parkinson's disease

BACKGROUND: Clinical symptoms of Parkinson's disease (PD) include not only motor distress, but also autonomic dysfunction. OBJECTIVE: To clarify the progression of autonomic nervous dysfunction in PD. METHODS: The subjects were 44 patients with de novo PD. Autonomic nervous function, including cardiac sympathetic gain, was evaluated on the basis of cardiac radioiodinated metaiodobenzylguanidine (MIBG) uptake, the response to the Valsalva maneuver, and spectral analyses of the RR interval and blood pressure. RESULTS: Decreased cardiac MIBG uptake was found even in patients with early stage PD. MIBG uptake gradually decreased with increased disease severity. Hemodynamic studies using the Valsalva maneuver revealed that patients with early stage PD had reduced baroreceptor reflex sensitivity (BRS) in phase II, but not phase IV. Blood pressures normally rose in phases II and IV, but the increments decreased with disease progression. In early stage PD, the low frequency power of the RR interval (RR-LF) and the ratio (LF/HF) of RR-LF to the high frequency component of the RR interval (RR-HF) were significantly lower than the respective control values, despite no significant difference in RR-HF; these variables decreased with disease progression. CONCLUSION: Our results show that latent sympathetic nervous dysfunction without parasympathetic dysfunction, especially that involving the sinus node, is already present in early stage de novo PD. It is unclear whether the responsible lesion is central or peripheral.