Cardiac uptake of [123I]MIBG separates Parkinson's disease from multiple system atrophy.

OBJECTIVE: To improve the differential diagnosis between patients with multiple system atrophy (MSA) and idiopathic PD (IPD) with autonomic failure. BACKGROUND: Some patients diagnosed with IPD are discovered to have alternative diseases such as MSA, despite the application of stringent diagnostic criteria. This differentiation is particularly difficult if patients with IPD also show symptoms of autonomic failure. In IPD, autonomic failure is caused by damage of the postganglionic part of the autonomic nervous system, whereas in MSA, degeneration of preganglionic and central autonomic neurons is revealed histopathologically. METHODS: Scintigraphy with [123I]metaiodobenzylguanidine (MIBG) enables the quantification of postganglionic sympathetic cardiac innervation. Fifteen patients with IPD and 5 patients with MSA underwent standard autonomic function tests and scintigraphy with MIBG. RESULTS: In all patients, cardiovascular testing showed evidence of autonomic failure of varying severity. In all patients with IPD, the heart-mediastinum (H/M) ratio of MIBG uptake was pathologically impaired, independent of duration and severity of autonomic and parkinsonian symptoms. All patients with MSA had a regular H/M ratio. Each patient could be assigned to the correct diagnostic group based on the results of the MIBG scintigraphy, even if the duration of the disease was only 2 years or less. CONCLUSIONS: This population assessment of the heart-mediastinum ratio of [123I]metaiodobenzylguanidine uptake showed a high sensitivity for the detection of autonomic involvement in patients with idiopathic IPD and also a high specificity for the discrimination between idiopathic PD and MSA.     

A useful marker for differential diagnosis of Parkinson's disease--MIBG myocardial scintigraphy]

We performed [123I]-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy in 180 patients with PD, 24 patients with DLB and 73 patients with the other related diseases. The heart-to-mediastinum (H/M) ratio in PD and DLB was significantly low compared to that in MSA, PSP, CBD and AD. The H/M ratio tended to decrease with the disease progression in PD. These findings suggest that MIBG myocardial scintigraphy could be a marker for differential diagnosis of PD and DLB. We immunohistochemically examined heart tissues from patients with pathologically confirmed PD, DLB and the other related diseases using monoclonal antibody against tyrosine hydroxylase (TH). The number of TH-immunoreactive nerve fibers in the epicardium was moderate or abundant in most patients with MSA, PSP, CBD and AD as well as in the control subjects. Contrarily, the number of TH-immunoreactive nerve fibers in the epicardium had almost completely disappeared in nearly all the patients with PD and DLB. These findings suggest that postganglionic cardiac sympathetic nerve denervation occurs in PD and DLB but not in MSA, PSP, CBD and AD, which accounts for the decreased cardiac uptake of MIBG in PD and DLB, but not in the other diseases.     

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.     

Abnormal cardiac [123I]‐meta‐iodobenzylguanidine uptake in multiple system atrophy

[¹²³I]‐Meta‐iodobenzylguanidine (MIBG) myocardial scintigraphy is useful for distinguishing multiple system atrophy (MSA) from Parkinson disease. In this study, longitudinal observation using MIBG myocardial scintigraphy was carried out in patients with MSA to evaluate the association of myocardial MIBG uptake with clinical features. A total of 96 MIBG examinations were performed in 52 patients with MSA. The heart/mediastinum (H/M) ratio of MIBG uptake at 240 minutes after injection was below the lower limit in 16 patients with MSA (31.3%). Overall, the H/M ratio correlated with neither disease duration nor severity. In the follow‐up observations, the H/M ratio did not show any specific trends, in contrast with the continuous decrease observed in patients with Parkinson's disease. This data clearly showed that cardiac MIBG uptake cannot necessarily be preserved in patients with MSA and that approximately 30% of patients with MSA showed decreased MIBG uptake without any correlation to disease duration or severity. © 2010 Movement Disorder Society     

Sequential imaging analysis using MIBG scintigraphy revealed progressive degeneration of cardiac sympathetic nerve in Parkinson’s disease

Background: Metaiodobenzylguanidine (MIBG) cardiac scintigraphy was used to differentiate Parkinson’s disease (PD) with Lewy body pathology from other degenerative parkinsonisms. MIBG cardiac scintigraphy demonstrates the extent of degeneration of myocardial post‐ganglionic sympathetic nerves in patients with PD. Because of its specificity for Lewy body (LB) pathology, MIBG scan might also be useful biomarker for the neurodegeneration attributed to PD. To estimate the utility of the imaging technique as a biomarker, we conducted sequential imaging analysis and power analysis. Methods: Sixty‐three patients who met the UK PD Society Brain Bank criteria were enrolled in this study. ¹²³I‐MIBG myocardial scintigraphy was performed on all subjects, and the heart to mediastinum (H/M) ratio was calculated. A second imaging session was carried out after a mean interval of 268 days. Results: Sequential imaging revealed a 2.9% decline of the H/M ratio from the baseline to the follow‐up image, which reached statistical significance, but the power analysis showed that a relatively large number of patients would be required to demonstrate the neuroprotective effects of any therapy. Conclusions: Sequential imaging using ¹²³I‐MIBG myocardial scintigraphy revealed progressive degeneration of the cardiac sympathetic nerve in 63 patients with PD. Although careful elimination of other disease conditions that damage the cardiac sympathetic nerve system is necessary, ¹²³I‐MIBG myocardial scintigraphy may be a useful addition to clinical trials that intend to prove neuroprotection among patients with PD.     

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.     

Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [¹²³I] MIBG myocardial scintigraphy, a sensitive biological marker for Parkinson’s disease (PD), is related to cardiac sympathetic denervation in patients with PD. A slight decrease in cardiac uptake of MIBG has also been reported in some patients with multiple system atrophy (MSA). However, the pathophysiological mechanism accounting for the slight decrease in MIBG uptake in MSA remains to be elucidated. For confirmation, we examined cardiac tissue and sympathetic ganglia from patients with MSA. We immunohistochemically examined each specimen of 15 patients with MSA together with 10 control subjects using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). The number of TH-immunoreactive nerve fibers in the epicardium was preserved in 8 of 15 patients with MSA as well as in 10 control subjects. The number of TH-immunoreactive, but not of NF-immunoreactive nerve fibers in the epicardium was mildly or moderately decreased in six patients with MSA, of whom four showed a decrease of TH immunoreactivity in the neuronal somata in the sympathetic ganglia. Moreover, TH- and NF-immunoreactive nerve fibers almost entirely disappeared in the heart of one patient with MSA, in whom Lewy body pathology was present in the sympathetic ganglia. These findings suggest that mild degeneration of the cardiac sympathetic nerve can occur in MSA which is closely related to the pathological change of neurons in the sympathetic ganglia, accounting for the slight decrease in cardiac uptake of MIBG. Moreover, concurrent Lewy body pathology in the sympathetic ganglia might accelerate cardiac sympathetic denervation even in MSA.     

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.     

Cardiac [123I]metaiodobenzylguanidine scintigraphy for vascular Parkinsonism.

The purpose of our study was to prospectively evaluate cardiac [(123)I]metaiodobenzylguanidine (MIBG) uptake in patients with cerebrovascular disease (CVD) who develop clinical symptoms of vascular Parkinsonism (VP). A total of 19 consecutive patients who developed Parkinsonism during the course of their CVD were enrolled in the study; 16 age-matched subjects, and 30 patients with Parkinson's disease (PD) were also evaluated with cardiac MIBG uptake. MIBG uptake was assessed using the ratio of the heart to the upper mediastinum (H/M) according to planar scintigraphic data. The mean H/M ratio was significantly higher in patients with VP than in those with PD (2.28 +/- 0.41 vs. 1.27 +/- 0.13; P < 0.001). MIBG uptake did not differ between VP and controls (2.46 +/- 0.33; P > 0.05). Our findings suggest that myocardial postganglionic sympathetic dysfunction found in PD is absent in most patients with VP. MIBG single photon emission computed tomography imaging may be useful to help distinguish between PD and VP patients in clinical practice.     

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.     

FP-CIT and MIBG scintigraphy in early Parkinson's disease.

Methods provided by nuclear medicine may be helpful in diagnosis of Parkinson's disease (PD). For that purpose, the sensitivity of iodine-123 metaiodobenzylguanidine ([123I]MIBG) scintigraphy and [123I]FP-CIT single photon emission computed tomography (SPECT) was studied in patients with PD onset (Hoehn and Yahr Stage 1). Cerebral [123I]FP-CIT and cardiac [123I]MIBG scintigraphy were carried out in 18 patients with idiopathic Parkinson's disease, according to Hoehn and Yahr Stage 1. For quantification purposes, we calculated the striatum/posterior lobe binding of FP-CIT and the heart-to-mediastinum (H/M) count ratio regarding MIBG scintigraphy. In 15 of 18 patients, we observed markedly reduced or asymmetric striatal FP-CIT tracer accumulation. FP-CIT binding of the affected striatum was significantly lower as compared with that of the unaffected side. Striatal FP-CIT binding correlated significantly with the motor part of the Unified Parkinson's disease rating scale (UPDRS) but not with age, disease duration, or gender. MIBG scintigraphy delivered significant pathological results in 13 of 18 patients. There was no significant correlation between the H/M ratio relating to MIBG scintigraphy and the motor part of UPDRS, age, disease duration, or gender; however, binding of striatal FP-CIT correlated significantly with cardiac MIBG accumulation. According to the clinical criteria, it might be difficult to prove the diagnosis of PD in patients with slight symptoms and in these cases, FP-CIT SPECT and MIBG scintigraphy may contribute to the early diagnosis of PD. In addition, the functional loss of nigrostriatal and cardiac sympathetic neurons seems to be coupled closely.     

Cardiac MIBG scintigraphy in Primary Progressive Freezing Gait

Freezing of gait (FOG) generally occurs as a late manifestation of Parkinson's Disease (PD). FOG, however, can present in isolation, constituting the so-called "Primary Progressive Freezing Gait"(PPFG). Myocardial (123)Metaiodiobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac nerve terminals. MIBG uptake reflects sympathetic system integrity, and reduced myocardial uptake of the tracer has been observed in nearly all patients with PD. We investigated MIBG uptake in 7 patients with PPFG, 14 patients with mild PD, and 6 patients with advanced PD and FOG (PD-FOG), and 18 control subjects. Our study shows that myocardial MIBG uptake was normal in all patients with PPFG (H/M ratio: mean+/-SD, 1.85+/-0.11 early; 1.71+/-0.15 delayed) and in the controls (H/M ratio: mean+/-SD, 1.94+/-0.18 early; 2.02+/-0.19 delayed) whereas it was markedly decreased in the patients with mild and advanced PD (H/M ratio: mean+/-SD, PD: 1.17+/-0.02 early; 1.16+/-0.02 delayed; PD-FOG: 1.22+/-0.10 early; 1.08+/-0.06 delayed). Our findings demonstrate that cardiac sympathetic denervation did not occur in patients with PPFG, confirming that PPFG and PD are distinct diseases.     

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.     

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.     

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 123I-MIBG scintigraphy can assess the disease severity and phenotype of PD

Objective: Cardiac ¹²³I-metaiodobenzylguanidine (MIBG) scintigraphy studies of patients with idiopathic Parkinson's disease (PD) found decreased uptake. Whether this decrease is associated with clinical severity as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the phenotypes of PD has not been determined. Methods: Cardiac MIBG scintigraphy was performed on 34 patients with PD, 7 with multiple system atrophy (MSA), 4 with dementia with Lewy bodies (DLB), and 11 normal controls (NCs). Early and delayed MIBG heart/mediastinum (H/M) ratios were evaluated. PD severity was assessed by the Hoehn and Yahr (H–Y) stage and UPDRS. Patients were grouped in two phenotypes, tremor and postural instability gait difficulty (PIGD)-dominant groups based on UPDRS components. Associations between MIBG uptake and age at onset, UPDRS, and disease phenotype were analyzed in each group. Results: The early H/M ratio was significantly lower in patients with PD (1.45±0.207) than in the NCs (2.08±0.231), and in those with MSA (1.99±0.284), but not in those with DLB (1.29±0.0435). The delayed H/M ratio for PD (1.33±0.276) also was significantly decreased as compared to the ratios for NCs (2.17±0.286) and MSA (2.16±0.414) but not DLB (1.16±0.0949). The early H/M ratio was significantly correlated with both UPDRS score and age at onset, whereas the delayed H/M ratio only was significantly correlated with age at onset. The PIGD-dominant group had significantly higher UPDRS scores and lower H/M ratios than the tremor-dominant group. Conclusion: Cardiac MIBG scintigraphy can be used to differentiate PD from MSA and NC, and to determine the disease severity and phenotypes of PD.     

Clinical and pathological study on early diagnosis of Parkinson's disease and dementia with Lewy bodies]

[123I] Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy has been used to evaluate postganglionic cardiac sympathetic innervation in heart diseases and some neurological disorders. To see clinical usefulness of MIBG myocardial scintigraphy to differentiate Parkinson's disease (PD) and dementia with Lewy bodies (DLB) from related movement disorders and Alzheimer disease (AD), we performed MIBG myocardial scintigraphy in patients with these disorders. Cardiac uptake of MIBG is specifically reduced in PD and DLB, and this imaging approach is a sensitive diagnostic tool that possibly differentiates PD and DLB from related movement disorders and AD. To see pathological basis of the reduced cardiac uptake of MIBG in Lewy body disease, we immunohistochemically examined cardiac tissues from patients with PD, DLB, related movement disorders and AD using antibodies against tyrosine hydroxylase (TH) and phosphorylated neurofilament (NF). Not only TH- but also NF-immunoreactive (ir) axons in the epicardial nerve fascicles were markedly decreased in Lewy body disease, namely cardiac sympathetic denervation, which accounts for the reduced cardiac uptake of MIBG in Lewy body disease. Patients with PD and DLB have Lewy bodies (LBs) in the nervous system, whereas patients with multiple system atrophy (MSA), progressive supranuclear palsy, corticobasal degeneration, parkin-associated PD and AD have no LBs in the nervous system. Even in patients with MSA, cardiac sympathetic denervation was associated with the presence of LBs. Therefore, cardiac sympathetic denervation is closely related to the presence of LBs in a wide range of neurodegenerative processes. Taken together, we conclude that the reduced cardiac uptake of MIBG is a potential biomarker for the presence of LBs. Because alpha-synuclein is one of the key molecules in the pathogenesis of PD, we further investigate how alpha-synuclein aggregates are involved in degeneration of the cardiac sympathetic nerve in PD. We immunohistochemically examined cardiac tissues from patients with incidental Lewy body disease (ILBD) and PD using antibodies against TH and phosphorylated alpha-synuclein. We found that (1) alpha-synuclein aggregates in the epicardial nerve fascicles, namely the distal axons of the cardiac sympathetic nerve, were much more abundant in ILBD with preserved TH-ir axons than in ILBD with decreased TH-ir axons and PD; (2) alpha-synuclein aggregates in the epicardial nerve fascicles were closely related to the disappearance of TH-ir axons; (3) in ILBD with preserved TH-ir axons, alpha-synuclein aggregates were consistently more abundant in the epicardial nerve fascicles than in the paravertebral sympathetic ganglia (pSG); and (4) this distal-dominant accumulation of alpha-synuclein aggregates was reversed in ILBD with decreased TH-ir axons and PD, which both showed decreased or depleted TH-ir axons but more abundant alpha-synuclein aggregates in the pSG. These findings indicate that accumulation of alpha-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system precedes that of neuronal somata or neurites in the pSG and that heralds centripetal degeneration of the cardiac sympathetic nerve in PD. This chronological and dynamic relationship between alpha-synuclein aggregates and distal-dominant degeneration of the cardiac sympathetic nervous system may represent the pathological mechanism underlying a common degenerative process in PD.     

Analysis of the relationship between muscle sympathetic nerve activity and cardiac 123I-metaiodobenzylguanidine uptake in patients with Parkinson's disease.

To analyze the correlation between muscle sympathetic nerve activity (MSNA) and cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD), we measured both parameters in 14 PD patients who were 51 to 82 years of age (mean, 63.1 +/- 8.7 years). The duration of PD was 2 to 26 years, and the disability level (modified Hoehn and Yahr stage) ranged from 2.0 to 4.0 (mean, 3.2 +/- 0.5). MSNA was recorded from the peroneal nerve fascicles using microneurographic methods, and then cardiac MIBG scintigraphy was performed within 1 month. We analyzed the correlation between the standardized MSNA, expressed as a percentage of the predicted value based on control subject data, and the heart-to-mediastinum ratio (H/M) or washout ratio (WR) from early and delayed MIBG images. The relationships between disease duration or disability and MSNA, the H/M ratio, or the WR were also analyzed. No significant correlations were found between MSNA and H/M ratio or WR. Although MSNA was inversely correlated with disease duration and with disability level, neither the H/M ratio nor the WR showed a significant correlation with disease duration or disability level. Because MSNA and MIBG abnormalities were not related, functional changes in addition to organic changes in cardiac sympathetic nerve endings may result in abnormal uptake of MIBG in Parkinson's disease. .     

Syncope and autonomic cardiovascular dysfunction in Parkinson disease

BACKGROUND AND PURPOSE : The aim of the study was to investigate the relationship between syncope or presyncope occurrence and dysfunction of the cardiovascular autonomic system in patients with Parkinson disease (PD). MATERIAL AND METHODS : Twenty-four PD patients were studied, including 10 subjects with syncope/presyncope and 14 con-trols without those symptoms. Ambulatory blood pressure monitoring (ABPM), Holter electrocardiographic monitoring, carotid sinus massage, tilt test, and cardiac scintigraphy with 123I metaiodobenzylguanidine (MIBG) were performed. RESULTS : Differences between the two groups were found in myocardial scintigraphy and ABPM. The stepwise regression analyses suggest that the values of late phase reduced uptake of MIBG (95% CI: 0.0-0.77; p < 0.05) and day-time minimum systolic blood pressure (95% CI: 0.78-0.98; p = 0.007) may be related to the occurrence of syncope/presyncope. CONCLUSIONS : The findings suggest an association between syncope/presyncope occurrence and dysfunction of the cardiovascular autonomic system in PD patients. Both 123I MIBG myocardial scintigraphy and ABPM may help identify a group of patients with an elevated risk for syncopic episodes which, in turn, may affect the choice of treatment.