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.     

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.     

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.     

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. .     

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.     

Differentiating Parkinson's disease from multiple system atrophy by [123I] meta-iodobenzylguanidine myocardial scintigraphy and olfactory test

We aimed to study whether either [¹²³l] myocardial meta-iodobenzylguanidine (MIBG) myocardial scintigraphy or the odor stick identification test for Japanese (OSIT-J) is effective in differentiating Parkinson’s disease (PD) from multiple system atrophy (MSA). We compared the MIBG accumulation and olfactory score between 42 PD and 42 MSA (19 MSA-P and 23 MSA-C) patients in the early stages. [¹²³l] MIBG myocardial scintigraphy showed higher sensitivity and the olfactory test higher specificity in differentiating PD from MSA. There were significant differences between PD and MSA-C (p = 0.0019) instead of MSA-P (p > 0.05) in the MIBG accumulation, while there were significant differences between PD and MSA-P (p = 0.0003) or MSA-C (p = 0.0003) in the OSIT-J score. Our data suggest that the olfactory test can be useful as a clinical tool with its higher specificity in differentiating PD from MSA in the early stages and, moreover, support the discrimination of PD from MSA-P.     

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.     

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.     

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.     

Relationship between ischemic stroke location and autonomic cardiac function

Autonomic cardiac dysfunction is a common complication after acute ischemic stroke (IS). We recruited 75 patients with acute IS with measurements of autonomic cardiac function, including heart rate variability (HRV) and associated parameters, and compared them with 81controls. Of the 75 patients, 28 had right hemispheric infarctions (RH), 29 had left hemispheric infarctions (LH), and 18 had brainstem infarctions (BS). A comparison of HRV in all patients with stroke and in control subjects showed significant differences between IS subgroups and controls in low frequency (LF), high frequency (HF), normalized LF, normalized HF, and LF/HF ranges. A post-hoc comparison identified significant differences between patients with IS with BS infarctions and the control group in LF, HF, and LF/HF ranges. BS infarction may cause a much greater increase in sympathetic modulation and reduced vagal activity compared to RH or LH infarction. Our findings provide evidence that acute IS causes significant damage to the cardiovascular autonomic system, manifesting as abnormalities of HRV. BS stroke might correlate with a significant reduction in parasympathetic and an increase in sympathetic influence on HRV.     

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.     

123I‐metaiodobenzylguanidine scintigraphy in Parkinson's disease and related disorders

Autonomic dysfunction is common in Lewy body disorders (Parkinson's disease, Dementia with Lewy Bodies, Pure Autonomic Failure, and REM sleep disorder). The loss of post‐ganglionic myocardial sympathetic nerve fibers is a prominent feature of autonomic dysfunction in such disorders. ¹²³I‐metaiodobenzylguanidine (MIBG) scintigraphy that visualizes catecholaminergic terminals in vivo is a biomarker used to detect cardiac sympathetic degeneration. Abnormal MIBG uptake has been consistently reported in Lewy body disorders. Some studies agree in the notion that increasing bradykinesia is related with an incremental cardiac sympathetic denervation, whereas tremor is not closely linked to cardiac denervation. “Atypical” parkinsonian syndromes, including Multiple System Atrophy, Progressive Supranuclear Palsy, and others, show modest reductions of cardial MIBG uptake. MIBG scintigraphy is moderately sensitive and specific in differentiating Parkinson's disease from such syndromes. Conversely, its sensitivity and specificity might be better in cognitively impaired patients, helping differential diagnosis between Dementia with Lewy Bodies, and Alzheimer disease. Confounding factors (comorbidities, comedications) should be carefully controlled before analyzing MIBG scintigraphy. © 2009 Movement Disorder Society     

Sympathetic skin response and cardiovascular autonomic function tests in Parkinson's disease and multiple system atrophy with autonomic failure.

The relationship between sympathetic skin response (SSR) and cardiovascular autonomic function tests (CVTs) was investigated in 15 patients with idiopathic Parkinson's disease (PD), 15 patients with clinical evidence of multiple system atrophy (MSA) with autonomic failure, and in 15 healthy control subjects. SSR was elicited by electrical stimulation of the right and left median nerves and simultaneously recorded on the palms of both hands. CVTs included the following sympathetic and parasympathetic tests: orthostatism, head-up tilt, cold pressor test, deep breathing, Valsalva maneuver, and hyperventilation. The SSR was normal in all patients with PD and control subjects but was abnormal or absent in all patients with MSA. For patients with MSA, SSR latency was significantly longer and amplitude was significantly smaller than that of patients with PD and control subjects. For patients with PD, SSR did not differ from that of control subjects. In these patients, SSR latency was significantly longer and SSR amplitude was smaller when the side with more marked motor symptoms was stimulated, both ipsilaterally and contralaterally to the side of stimulation. A statistically significant difference in SSR latencies and amplitudes was found between patients with PD and control subjects only when motor asymmetries were considered. CVTs showed severe sympathetic and parasympathetic hypofunction in patients with MSA, but not in patients with PD or control subjects. No correlation was found between SSR and CVTs that assess sympathetic function in patients and control subjects. SSR is indicated as an additional test for the evaluation of sympathetic degeneration in patients with MSA.     

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.     

Odour identification test and its relation to cardiac 123I-metaiodobenzylguanidine in patients with drug induced parkinsonism

We investigated olfactory function and its relation to cardiac 123I-metaiodobenzylguanidine (MIBG) uptake in 15 patients with drug induced parkinsonism (DIP). The mean Cross Cultural Smell Identification (CCSI) score was significantly greater in patients with DIP than in those with Parkinson's disease (PD: 6.9 (1.6) vs 4.4 (2.2); p<0.001); however, the mean CCSI score in patients with DIP was not significantly different from controls. One patient with DIP, whose CCSI score was significantly reduced, also exhibited decreased cardiac MIBG uptake. DIP patients with CCSI scores within the normal range had normal cardiac MIBG uptake. Our study suggests that an olfactory function test may be a useful tool for detecting DIP unrelated to PD and for identifying patients with DIP who have subclinical PD.     

嗅觉功能检查在帕金森病诊断中的应用

目的 探讨帕金森病(Parkinson's disease,PD)患者的嗅觉功能改变特点.方法 对37例临床确诊的50岁以上PD患者和95名年龄匹配的健康中老年人进行T&T主观嗅觉识别阈测试和嗅觉事件相关电位(olfactory event related potentials,OERP)检查,比较其主观嗅觉识别阈和嗅觉事件相关电位P2潜伏期的差异.结果 ≥70岁的PD患者左、右侧鼻腔主观嗅觉识别阈分别为4.6±1.1、4.4±1.2,<70岁PD患者左、右侧鼻腔主观嗅觉识别阈分别为3.9±1.7、4.0±1.7;≥70岁的对照组左、右侧鼻腔主观嗅觉识别阈分别为0.4±0.9、0.4±0.9,<70岁对照组左、右侧鼻腔主观嗅觉识别阈分别为0.5±0.8、0.5±0.8;PD患者组的主观嗅觉识别阈明显高于对照组(t=15.246、15.378、8.664、8.776,P<0.01);≥70岁的PD患者左、右侧鼻腔OERP P2潜伏期分别为(734.9±143.2)、(696.1±165.9)ms,<70岁的PD患者左、右侧鼻腔OERP P2潜伏期分别为(730.5±159.4)、(719.5±159.2)ms;≥70岁的对照组左、右侧鼻腔OERP P2潜伏期分别为(547.9±65.0)、(558.5±56.3)ms,<70岁的对照组左、右侧鼻腔OERP P2潜伏期分别为(523.3±61.9)、(526.8±62.0)ms,OERP P2潜伏期则明显长于对照组(t=-3.940、-3.750、-7.514、-8.205,P<0.01);同时PD患者组的主观嗅觉识别阈和OERP的异常率明显高于对照组.结论 PD患者主观嗅觉识别阈测试和OERP P2潜伏期结果 明显比对照组差,提示嗅觉功能减退是PD的重要临床表现;嗅觉功能检查可以作为PD筛查、诊断的参考指标.