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.     

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.     

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.     

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.     

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.     

Autonomic dysfunction in parkinsonian LRRK2 mutation carriers

IntroductionThe aim of this study was to compare autonomic function in PD symptomatic carriers of the LRRK2 mutations and idiopathic Parkinson's disease (iPD) patients.Material and methodsWe studied 25 PD patients: 12 with the LRRK2 mutation (6 G2019S and 6 R1441G), and 13 with iPD. All patients underwent blood pressure and heart rate monitoring during head up tilt, Valsalva maneuver and deep breathing, along with recording of sympathetic skin response (SSR) and cardiac MIBG scintigraphy.ResultsThree of the patients with iPD and one of the LRRK2 carriers had orthostatic hypotension. Arterial pressure “overshoot” during phase IV of Valsalva maneuver was less pronounced in patients with iPD. During passive tilt, LRRK2 carries had higher increase of blood pressure than iPD patients MIBG late myocardial/mediastinal uptake ratios were higher in LRRK2 mutation carriers (1.51 ± 0.28 vs 1.32 ± 0.25; p < 0.05).DiscussionCarriers of the LRRK2 mutation had less autonomic impairment than those with iPD as shown by higher cardiac MIBG uptake and a tendency to less impairment of autonomic non-invasive tests. It is important to carry out larger studies comparing the clinical, functional and pathological characteristics of these patients.     

The clinical significance of MIBG myocardial scintigraphy in Parkinson disease

Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy can assess postganglionic presynaptic cardiac sympathetic nerve endings. Reduced cardiac MIBG uptake on MIBG myocardial scintigraphy has been reported in patients with Parkinson disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and familial PD linked to SNCA duplication. This imaging procedure is a sensitive diagnostic tool that might differentiate PD and DLB from other movement disorders from Alzheimer disease (AD). We recently reported cardiac sympathetic denervation in PD, DLB, PAF, and familial PD linked to SNCA duplication which accounts for the reduced cardiac MIBG uptake in these disorders. The patients with PD, DLB, PAF and familial PD linked to SNCA duplication have Lewy bodies in the nervous system, whereas patients with multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration, AD, and parkin-associated PD do not. However, in patients with MSA or PSP, cardiac sympathetic denervation was associated with the presence of Lewy bodies in the nervous system. Therefore, cardiac sympathetic denervation is closely related to the presence of Lewy bodies in the wide range of neurodegenerative processes. Thus, we conclude that reduced cardiac MIBG uptake is a potential biomarker for the presence of Lewy bodies in the nervous system. We infer that MIBG myocardial scintigraphy is a noninvasive tool for detecting Lewy bodies during life.     

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.     

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.     

Impaired cardiovascular autonomic function in Parkinson's disease with visual hallucinations.

We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD). The subjects were 37 patients without VH (VH(-)) and 31 with VH (VH(+)). Autonomic function was evaluated on the basis of cardiac 123-radioiodinated metaiodobenzylguanidine (123I-MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by tilt-table testing. 123I-MIBG uptake was lower in VH(+) than VH(-). Hemodynamic studies showed that VH(-) had only cardiac sympathetic and parasympathetic dysfunction, while VH(+) additionally had reduced vasomotor sympathetic functions. The fall in SBP during tilt-table testing was greater in VH(+) than VH(-). NE and its difference in the supine and upright positions were decreased in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more severe in VH(+) than in VH(-). Severe dysfunction in PD with VH is probably attributed to Lewy-body lesions or neuronal loss in sympathetic ganglia, the central autonomic system, or both.     

Relation between autonomic dysfunction and progression of Parkinson's disease]

It has been claimed that cardiovascular dysfunction in patients with Parkinson's disease is less severe than multiple system atrophy. Autonomic dysfunction, however, increases with progression of Parkinson's disease. We studied the relation between autonomic dysfunction and disease severity by cardiovascular function testing with the Valsalva maneuver. The study group comprised 20 healthy controls (age, 52.7 +/- 13.6 years) and 31 patients with Parkinson's disease (59.0 +/- 7.2 years), including 13 who were previously untreated (55.0 +/- 6.2 years) and 18 who were receiving levodopa (61.8 +/- 7.1 years). The Valsalva maneuver was done having the subject exhale into a mouthpiece with an expiratory pressure of 40 mmHg for 15 seconds. Blood pressure and RR interval were measured during the Valsalva maneuver by tonometry, using a non-invasive 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. BRS II, BRS IV, and IVp in the patients of Parkinson's disease were significantly lower than those of healthy controls. BRS II, BRS IV, and IIp, however, did not significantly differ between the previously untreated patients and healthy controls. IVp of the previously untreated patients was significant lower than that of healthy controls. BRS II and BRS IV of patients with Parkinson's disease who were receiving levodopa for less than 5 years were significantly lower than those of the healthy controls. BRS II, BRS IV, and IIp decreased as disease duration increased, while IVp was unrelated to disease duration. These results suggest that patients with early Parkinson's disease have cardiac sympathetic autonomic dysfunction with maintained baroreceptor reflex sensitivity. Reduced baroreceptor reflex sensitivity was associated with levodopa treatment in patients with Parkinson's disease. Baroreceptor reflex sensitivity decreased and vasomotor sympathetic autonomic dysfunction developed as duration of disease increased.     

Autonomic dysfunction in Machado-Joseph disease

OBJECTIVE: Machado-Joseph disease is an autosomal dominant spinocerebellar ataxia with expanded trinucleotide repeats. Although autonomic nervous system degeneration was documented in postmortem reports, the autonomic dysfunction in patients with Machado-Joseph disease, either in clinical analysis or electrophysiological investigations, has not yet been studied in detail. METHODS: Fifteen patients with genetically confirmed Machado-Joseph disease and 34 healthy subjects were studied. The study design included a detailed questionnaire, R-R interval variation on deep breathing or Valsalva maneuver, and sympathetic skin response evoked by electrical stimulation of the median nerve or magnetic stimulation of the neck. RESULTS: Sixty-seven percent of patients had at least 3 symptoms involving different aspects of autonomic functions. Voiding problems and thermoregulatory disturbance were the most common symptoms. Ten (71%) of 14 patients had abnormal R-R interval variation with a significant reduction of the mean ratio. Prolonged latency or absence of sympathetic skin response to electrical stimulation was identified in 73% of patients and to magnetic stimulation, in 53%. R-R interval variation and sympathetic skin response showed good correlation with the functional stage. Electrical stimulation revealed the highest sensitivity, specificity, and positive predictive value compared with other tests. CONCLUSION: The present investigation documents that autonomic dysfunction is not uncommon in patients with Machado-Joseph disease and might be related to the clinical progression.     

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.     

I-123 MIBG cardiac scintigraphy and autonomic test evaluation in multiple sclerosis patients

Autonomic symptoms are common in multiple sclerosis (MS) patients and may cause significant disability. The purpose of this study was to evaluate direct cardiac sympathetic denervation in MS patients with I-123 MIBG cardiac scintigraphy compared with other parasympathetic electrophysiological examinations of autonomic dysfunction. Ten patients with MS and 7 age- and sex-matched control subjects were prospectively evaluated. The neurological deficit and disability stages of the patients were rated according to the Kurtzke Expanded Disability Status Scale (EDSS). Autonomic tests included the R-R interval, Valsalva ratio and standup test. All patients and control subjects had planar and SPECT cardiac scintigraphy with I-123 MIBG injection. Seven MS patients had relapsing-remitting (R-R) type and three had secondary progressive type (SP). A pathological MIBG cardiac washout rate was found in 3/10 MS patients, all of them with SP-MS. The other seven had normal washout rates. No correlation was found between the scan and the individual parasympathetic autonomic test results. I-123 MIBG myocardial scintigraphy may detect direct disturbances of the sympathetic cardiac function in patients with MS in addition to parasympathetic dysfunction tests and can be an important additional means of assessing autonomic pathways. Determination in MS of the co-existence of autonomic dysfunction, especially the cardiac sympathetic involvement in the SP type, may aid in evaluation of disease severity and cardiac function follow-up. All departments are affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Israel.     

Autonomic involvement in Parkinson's disease: pathology, pathophysiology, clinical features and possible peripheral biomarkers

Autonomic nervous system involvement occurs at early stages in both Parkinson's disease (PD) and incidental Lewy body disease (ILBD), and affects the sympathetic, parasympathetic, and enteric nervous systems (ENS). It has been proposed that alpha-synuclein (α-SYN) pathology in PD has a distal to proximal progression along autonomic pathways. The ENS is affected before the dorsal motor nucleus of the vagus (DMV), and distal axons of cardiac sympathetic nerves degenerate before there is loss of paravertebral sympathetic ganglion neurons. Consistent with neuropathological findings, some autonomic manifestations such as constipation or impaired cardiac uptake of norepinephrine precursors, occur at early stages of the disease even before the onset of motor symptoms. Biopsy of peripheral tissues may constitute a promising approach to detect α-SYN neuropathology in autonomic nerves and a useful early biomarker of PD.     

Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient with Parkinson disease

Decreased cardiac uptake in (123)I-metaiodobenzylguanidine (MIBG) scintigraphy has been adopted as one of the most reliable diagnostic tests for Parkinson disease (PD) in Japan. To investigate the morphological basis for this finding, we performed a detailed neuropathological study of the cardiac sympathetic nervous system of a 71-year-old autopsy-proven PD patient, who presented with a marked decrease in cardiac uptake of MIBG, just 1 year prior to death. We carefully examined the intermediolateral column at several levels of the thoracic spinal cord, the sympathetic trunk and ganglia, and the nerve plexus of the anterior wall of the left ventricle and compared the findings with those of five age-matched controls. We found that the cardiac plexus was more heavily involved than the sympathetic ganglia in this patient with PD. Our study may provide further evidence that the markedly decreased cardiac uptake of MIBG observed in PD cases represents preferential involvement of the cardiac sympathetic nerve plexus in this disorder.     

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.     

Impaired cardiac uptake of meta-[123 I]iodobenzylguanidine in Parkinson's disease with autonomic failure

Objective – To selectively investigate postganglionic sympathetic cardiac neurons in patients with Parkinson's disease and autonomic failure. Material and methods – Metaiodobenzylguanidine (MIBG) is a pharmacologically inactive analogue of noradrenaline, which is similarly metabolized in noradrenergic neurons. Therefore the uptake of radiolabeled MIBG represents not only the localization of postganglionic sympathetic neurons but also their functional integrity. Ten patients with Parkinson's disease and autonomic failure underwent standardized autonomic testing, assessment of catecholamine plasma levels and scintigraphy with [¹²³ I]MIBG. Results – The cardiac uptake of MIBG, as demonstrated by the heart/mediastinum ratio, was significantly lower in patients in comparison with controls. Scintigraphy with MIBG allowed the selective in-vivo investigation of postganglionic sympathetic cardiac efferents in patients with autonomic failure, a procedure which was previously confined to post-mortem examination. Conclusion – These findings point to a relevant postganglionic pattern of involvement of the autonomic nervous system (ANS) in Parkinson's disease and autonomic failure.     

Autonomic dysfunction according to disease progression in Parkinson's disease

BackgroundAlthough autonomic dysfunction is common in patients with Parkinson’s disease (PD), few data are available regarding its pattern and quantitative severity with increasing Hoehn and Yahr (H&Y) stage. We conducted autonomic function tests to quantify autonomic dysfunction in PD patients and to elucidate its possible relationship with disease progression.MethodsWe performed autonomic function tests including Valsalva ratio, heart rate response to deep breathing, quantitative sudomotor axon reflex test, and head-up tilt test in 66 patients with PD. We compared clinical characteristics and results of autonomic function tests between stages, and correlated the proportion of abnormal patients in each test with their H&Y stage. In addition, logistic regression analyses were conducted to examine the contribution of increasing H&Y stage to impairments of each domain of the autonomic nervous system.ResultsWe found that PD patients with higher disease stage tended to have impairments in cardiovagal and sudomotor domains of the autonomic nervous system. Cardiovagal function was the domain most influenced by disease progression. Our findings also demonstrated that the pattern of sudomotor impairment in PD was similar to that in patients with peripheral autonomic neuropathy.ConclusionsOur study demonstrates that autonomic dysfunction is not only common in early stage PD but it increases in severity with increasing disease stage. Given that the patterns of sudomotor impairments in PD are similar to those in peripheral neuropathy, our data support a previous hypothesis that pathophysiology of PD involves both the central and peripheral nervous systems.     

A clinical role for [(123)I]MIBG myocardial scintigraphy in the distinction between dementia of the Alzheimer's-type and dementia with Lewy bodies

OBJECTIVE: Scintigraphy with [(123)I]metaiodobenzyl guanidine ([(123)I]MIBG) enables the quantification of postganglionic sympathetic cardiac innervation. Recently, myocardial [(123)I]MIBG scintigraphy has been found to be useful in distinguishing Parkinson's disease, a Lewy body disease, from other akinetic rigid syndromes. Some patients initially diagnosed with dementia of the Alzheimer's type (DAT) are discovered to have an alternative disease such as dementia with Lewy bodies (DLB), despite the application of stringent diagnostic criteria. In the present study, examinations were performed to clarify the usefulness of myocardial [(123)I]MIBG scintigraphy in improving the differential diagnosis between patients with DLB and DAT. METHODS: Fourteen patients with DLB and 14 patients with DAT underwent scintigraphy with [(123)I]MIBG, combined with orthostatic tests and cardiac examinations. RESULTS: In all patients with DLB, the heart to mediastinum (H/M) ratio of MIBG uptake was pathologically impaired in both early and delayed images, independently of the duration of disease and autonomic failure. All patients with DAT had successful MIBG uptake in the heart regardless of duration of disease and autonomic failure. Orthostatic hypotension was seen in four patients with DAT and 13 patients with DLB. CONCLUSIONS: [(123)I]MIBG myocardial scintigraphy might detect early disturbances of the sympathetic nervous system in DLB and might provide useful diagnostic information to discriminate DLB from DAT. The distinction between DLB and DAT may be improved by greater emphasis on cardiac sympathetic disturbances.