123I-metaiodobenzylguanidine Uptake Research Articles

Idiopathic REM Sleep Behavior Disorder: Implications for the Pathogenesis of Lewy Body Diseases.

Objectives. Both results of the odor identification and cardiac 123I-metaiodobenzylguanidine accumulation have been investigated for their potential to enhance the detection of pathogenesis resembling that of Lewy body-related α-synucleinopathies in patients clinically diagnosed as having idiopathic REM sleep behavior disorder. Methods. We performed both the Odor Stick Identification Test for Japanese and 123I-metaiodobenzylguanidine scintigraphy in 30 patients with idiopathic REM sleep behavior disorder, 38 patients with Parkinson's disease, and 20 control subjects. Results. In idiopathic REM sleep behavior disorder, reduced odor identification score and an early or delayed heart to mediastinum ratio on 123I-metaiodobenzylguanidine were almost as severe as in Parkinson's disease patients. Delayed cardiac 123I-metaiodobenzylguanidine uptake was even more severe in the idiopathic REM sleep behavior disorder group than in the Parkinson's disease group. Conclusions. Reduced cardiac 123I-metaiodobenzylguanidine uptake, which is independent of parkinsonism, may be more closely associated with idiopathic REM sleep behavior disorder than olfactory impairment.

Autonomic nervous system dysfunction in advanced systolic heart failure

BackgroundAn alteration of the autonomic nervous system has been described in heart failure (HF). The aim of this study was to assess, compare and relate the impairment of both arms of the autonomic nervous systems, the sympathetic and parasympathetic (SNS and PNS) in a same group of patients. MethodsWe analyzed 23 patients with advanced HF (NYHA III–IV/IV and IV/IV) and EF<35% who were on the waiting list for heart transplantation. We assessed the SNS by determining cardiac uptake of 123I metaiodobenzylguanidine, and analyzed the heart mediastinum rate (HMR) and the myocardial washout rate (WR). The PNS was assessed by 24-hour Holter ECG recording and subsequent analyses of heart rate turbulence (HRT) in which turbulence onset (TO) and turbulence slope (TS) were determined. ResultsIn the study of the SNS, HMR values were1.32±0.12, and WR 0.36±0.1. Higher creatinine levels were associated with a lower WR (r=−0.604; p=0.02). In the study of the SNP, TO was higher the lower the LVEF (r=−0.410; p=0.052), and age was associated with a lower TS (r=−0.4; p=0.059). In the study of the relationships between the SNS and PNS, HMR was correlated in a nearly significant manner with TO (r=−0.399; p=0.059) and WR with TS (r=−0.447; p=0.033). ConclusionsIn stable patients with advanced HF (NYHA III–IV and IV/IV), a significant and parallel impairment occurs in both arms of the autonomic nervous system. This could have prognostic implications and would help to prioritize patients on the waiting list for heart transplantation.

Lowered cardiac sympathetic nerve performance in response to exercise in Parkinson's disease

We examined whether cardiac sympathetic denervation influences the cardiovascular response to exercise in Parkinson's disease (PD). Sixteen patients with PD were divided into two groups, according to their cardiac uptake of (123)I-metaiodobenzylguanidine (denervated group, 10 patients with heart to mediastinum (H/M) ratio < 1.7; innervated group, six patients with H/M ratio > 1.7) and compared changes in blood pressure (BP), heart rate (HR), and cardiac contractility with 13 control subjects during ergometric exercise stress. Velocity index (VI), an indicator of cardiac contractility, was measured using impedance cardiography and recorded every minute. Exercise began at a power output of 20 W for the first 2 min and increased 10 W every 2 min to a maximal intensity of 60 W. All control subjects accomplished the procedure while six patients with PD could not continue after the first minute of 50 W loading. There were no significant differences in BP or HR change between the three groups. However, a significant reduction in VI was observed from the first minute of the 30 W workload in the denervated group compared to the control group. This lowered response continued till 50 W loading and was significantly different to the innervated group at 50 W loading. No significant VI changes were observed between the control and innervated groups throughout the exercise test. Patients with PD with reduced MIBG uptake had a lowered cardiac contractility than innervated subjects during exercise, suggesting that this response represents the impaired exercise capacity of patients with PD with cardiac sympathetic denervation.

I-123 MIBG cardiac uptake measurements: limitations of collimator choice and scatter correction in the clinical context

Low uptake of metaiodobenzylguanidine (MIBG) in patients with heart failure generally indicates poor prognosis. Our objective was to determine the best method for calculating I-123 MIBG uptake. MIBG uptake as a percentage of the injected dose is presented as an alternative method for serial assessment. Patients with chronic heart failure were imaged with I-123 MIBG with both a medium-energy (ME) collimator and a low-energy high-sensitivity (LEHS) collimator. Scatter correction was used to correct the LEHS images. Heart-to-mediastinal (H/M) ratio and the percentage of myocardial uptake of MIBG were obtained. Mean H/M ratios for the ME images, LEHS images and scatter-corrected LEHS images were 2.45+/-0.61, 2.22+/-0.47 and 2.51+/-0.62, respectively. Mean H/M ratio was significantly different among all the three sets (P<0.001) of images. The average difference in H/M ratios between the ME images and LEHS images was lower when scatter correction was applied (4.95% vs. 9.79%). The error in calculating the myocardial uptake as a percentage of the injected dose was significantly lower than the error in calculating H/M ratio (0.2 vs.10.2% LEHS; 0.3 vs.16.0% ME; 0.2 vs.11.8% LEHS scatter corrected). For quantitative assessment of H/M ratio in I-123 MIBG imaging a LEHS collimator can be used in place of a ME collimator to achieve better counting statistics, but scatter correction must be used. The calculation of the myocardial uptake as a percentage of the injected dose has potential as an alternative method of measurement, particularly for serial assessment.

Cardiac adrenergic nerve function in patients with cardiac syndrome X

We previously found a severe impairment of cardiac uptake of I-metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, on myocardial scintigraphy in a small group of patients with cardiac syndrome X (CSX), suggesting a dysfunction of cardiac adrenergic nerve fibres. In this study, we assessed the consistency of these previous findings in a larger group of these patients. Planar and single-photon emission computed tomography MIBG myocardial scintigraphy was performed in 40 CSX patients (58 +/- 7 years, 17 men). Cardiac MIBG uptake was measured by the heart/mediastinum ratio and by a single-photon emission computed tomography regional cardiac MIBG uptake defect score (higher values = lower uptake). As a control group, we studied 20 healthy individuals (56 +/- 6 years, nine men). An exercise stress Tc-SestaMIBI myocardial scintigraphy was performed in 34 CSX patients (85%). Cardiac MIBG defects were observed in 30 patients (75%), with nine (22.5%) showing no cardiac MIBG uptake at all. Compared with controls, CSX patients showed a significantly lower heart/mediastinum ratio (1.70 +/- 0.35 vs. 2.1 +/- 0.22, P < 0.001) and a higher cardiac MIBG defect score (27 +/- 25 vs. 4.4 +/- 2.5, P < 0.001). No differences were found in lung MIBG uptake between the two groups. Reversible perfusion defects on stress myocardial scintigraphy were found in 17 out of 34 CSX patients (50%), all of whom also had abnormal cardiac MIBG uptake; cardiac MIBG uptake abnormalities were also present in nine of 17 patients with normal perfusion scintigraphic images. Cardiac MIBG uptake findings were similar in our first 12 patients and in the 28 patients studied subsequently. Our data show a relevant impairment of cardiac MIBG uptake in patients with CSX, suggesting that functional abnormalities in cardiac adrenergic nerve function may play a significant role in the mechanisms responsible for the syndrome.

Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson's disease

We investigated cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) in patients with REM sleep behavior disorder (RBD) and compared the findings with those of idiopathic Parkinson's disease (IPD). Thirteen RBD, 222 IPD and 50 controls underwent cardiac 123I-MIBG scintigraphy. Resulting heart-to-mediastinum (H/M) ratios were significantly lower in patients with RBD and IPD as compared to the control ratios. H/M ratios were lower for delayed than for early images in patients with RBD and IPD; whereas, the controls had higher ratios for delayed images. H/M ratios were significantly lower for patients with RBD than for those with IPD at Hoehn and Yahr stages 1 and 2. Disease duration did not differ between the two groups. Our study revealed that cardiac 123I-MIBG uptake was more markedly reduced in patients with RBD than in those with early stage IPD. RBD may not necessarily be a prodromal condition of IPD with respect to cardiac 123I-MIBG uptake results.

Long-term follow-up of “reversible” dilated cardiomyopathy with improvement of cardiac sympathetic nerve activity after cardiac resynchronization therapy (CRT): Do “CRT superresponders” have “dyssynchrony-induced cardiomyopathy”?

We report a case of idiopathic dilated cardiomyopathy with severe heart failure and complete left bundle branch block (CLBBB) which exhibited an excellent response to cardiac resynchronization therapy (CRT). A 71-year-old male had been treated for 9 years with medication for chronic heart failure. He was referred to hospital with a complaint of dyspnea. An electrocardiogram showed CLBBB, with a QRS-width of 200ms. Markedly dilated left ventricular (LV) chamber with a low ejection fraction (EF) of 18% and severe mitral regurgitation were registered by echocardiogram. Myocardial neuronal 123I-metaiodobenzylguanidine uptake was reduced, with a heart-to-mediastinum (H/M) ratio of 1.88. Immediately after the introduction of CRT, clinical improvement was observed. At 1-year follow-up, LV chamber size and cardiac function were almost normalized, with an EF of 53%. Cardiac sympathetic nerve activity (CSNA) was simultaneously normalized, with an H/M ratio of 2.32 and a washout rate of 14.7%. However, after the cessation of carvedilol administration, CSNA and LV systolic function were slightly aggravated, with an H/M ratio of 2.20, a washout rate of 15.9%, and an EF of 44%. In the present case, the excellent improvement in cardiac function and CSNA was caused by the combined effects of beta-blocker therapy and CRT.

Cardiac adrenergic nerve function and microvascular dysfunction in patients with cardiac syndrome X

Objective:To assess whether abnormalities in cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction in patients with cardiac syndrome X (CSX).Setting:University hospital.Patients:29 patients (aged 59 (SD 7) years, 11...

Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy

The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV-LV) and intraventricular (SD-RV and SD-LV) asynchrony were computed. Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 +/- 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified.

I-123 Metaiodobenzylguanidine (MIBG) in Sympathetic Denervation and Reinnervation of Salivary Glands in a Child With Cervical Neuroblastoma

Asymmetric I-123 MIBG uptake in salivary glands in children with cervical neuroblastoma has been reported previously, in association with Horner syndrome. We present the case of a 9-month-old male infant with a surgically excised right-sided cervical neuroblastoma, no manifestations of oculosympathetic paresis, and no visualization of the right-sided salivary glands in postoperative I-123 MIBG imaging. Six months later faint I-123 MIBG uptake was observed in the right parotid and submandibular salivary glands and this became more intense in subsequent scans. These findings are consistent with sympathetic denervation and reinnervation of the salivary glands and illustrate the plasticity of the sympathetic nervous system.

Cardiac sympathetic dysautonomia in children with chronic kidney disease

The pathophysiology of cardiovascular disease (CVD) in chronic kidney disease (CKD) remains uncertain, but autonomic dysfunction seems to be involved. The aim of the study is to investigate the cardiac dysautonomia in uremic pediatric individuals through iodine 123 metaiodobenzylguanidine (MIBG) scintigraphy and heart rate variability (HRV) analysis. We divided 40 CKD patients (aged 5-21 years) into 4 groups according to the treatment for CKD: conservative (n = 7), continuous ambulatory peritoneal dialysis (n = 5), hemodialysis (n = 13), and kidney transplantation (n = 15). Planar and tomographic I-123 MIBG images were acquired, and early and late cardiac uptake, cardiac and lung washout, and regional I-123 MIBG uptake were evaluated. Hemodialysis patients showed increased cardiac washout (P = .002), a heterogeneous pattern of I-123 MIBG distribution (P = .036), and lower values of the low-frequency (LF) component of HRV (P = .040). Subjects undergoing continuous ambulatory peritoneal dialysis had reduced lung washout (P = .030). The cardiac washout correlated positively with parathyroid hormone levels and negatively with creatinine clearance. There was a significant negative association between the LF component and cardiac washout. Uremic cardiac dysautonomia may be characterized by a decreased LF component of HRV, increased I-123 MIBG washout, and a heterogeneous distribution pattern in the left ventricular walls; these abnormalities were not present after kidney transplantation.

Lung-uptake and -washout of MIBG in sarcoidosis

The aim of this study was to evaluate the uptake and -washout of I-123 meta-iodobenzylguanidine (MIBG), reflecting norepinephrine metabolism, in the lungs in patients with sarcoidosis. Lung I-123 MIBG kinetics was assessed in 43 patients with sarcoidosis. The range of disease duration was 1-16 years (median: 3 years). Thirteen patients had radiographic stage 0-I, 30 patients had radiographic stage II-IV. Serological clinical parameters and small fibre neuropathy, as assessed by temperature threshold testing (TTT) were measured in 39/43 patients. 31/39 patients had an abnormal TTT. Eleven healthy controls participated in this study. Both dual head planar and dual headed SPECT images of the thoracic regions were made. The uptake of I-123 MIBG and the washout percentage were calculated in sarcoidosis patients and compared with the healthy persons. Lung I-123 MIBG uptake in patients with sarcoidosis did not differ from controls. The lung washout of I-123 MIBG was significantly (p<or=0.01) decreased in sarcoidosis. Remarkably this was most clearly seen in patients with an abnormal TTT and in patients with more advanced radiographic pulmonary involvement (radiographic stages II-IV) but not in patients with decreased lung function (FVC<80% or DLCO<80%). The inflammatory process of the lungs in sarcoidosis seems not to affect pulmonary vasculature. In sarcoidosis decreased lung washout of I-123 MIBG might, at least partly, be explained by sympathetic autonomic nerve dysfunction. Future studies are needed to explore the clinical relevance of this observation.

Reduced cardiac 123 I-MIBG scintigraphy in idiopathic REM sleep behavior disorder

Idiopathic REM sleep behavior disorder (RBD) may represent prodromal synucleinopathies. We report markedly reduced cardiac (123)I-metaiodobenzylguanidine uptake, consistent with the loss of sympathetic terminals, in idiopathic RBD. We also demonstrate that this reduction is of the same magnitude as that found in patients with Parkinson disease. The results are consistent with the hypothesis that idiopathic RBD in older patients is a forme fruste of Lewy body disease.

Phenylephrine and pilocarpine eye drop test for dementia with Lewy bodies and Alzheimer's disease

Pupillary response test using dilute phenylephrine, a sympathetic agonist, and dilute pilocarpine, a cholinergic agonist, were performed in 24 patients with dementia with Lewy bodies (DLB), 40 patients with Alzheimer's disease (AD), and 23 normal elderly subjects. The mydriatic response to 0.5% phenylephrine was significantly greater in the DLB group than in the AD and control groups. The mydriatic change correlated inversely with the reduction in cardiac 123I-metaiodobenzylguanidine uptake. In contrast, miotic response to 0.0625% pilocarpine was significantly greater in the DLB and AD groups than in the control group. The pupil assay using combined phenylephrine and pilocarpine eye drop test may be useful in the detection of patients with DLB and AD and in distinguishing between them.

Myocardial 123I-MIBG scintigraphy in patients with PSP, CBD and MSA

Reduced cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) is considered to represent dysfunction of the postganglionic neurons of the cardiac sympathetic nervous system. Evidence indicates that cardiac uptake of 123I-MIBG is decreased in patients with idiopathic Parkinson’s disease (IPD), dementia with Lewy bodies (DLB) and pure autonomic failure (PAF), which have common pathological features with Lewy body formation. In the present article, we review previous reports that determined heart-mediastinum (H/M) ratios in early and delayed images of patients with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) in comparison to those of IPD and controls. The majority of reports suggest that H/M ratios of patients with PSP, CBD and MSA are comparable to those of controls, while H/M ratios of patients with IPD are significantly reduced. This reduction seen in IPD may reflect the loss and/or dysfunction of postganglionic cardiac sympathetic nerve terminals. Several authors reported mild reduction of 123I-MIBG uptake in patients with MSA and PSP. However, no degeneration of postganglionic neurons of the cardiac sympathetic nervous system has been detected in patients with these diseases. These results indicate that cardiac 123I-MIBG uptake is a sensitive tool with which to differentiate IPD from neurodegenerative diseases with extrapyramidal symptoms such as PSP, CBD and MSA.

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.

1064 An analysis of the relationship between muscle sympathetic nerve activity and cardiac 123I-metaiodobenzylguanidine uptake in patients with Parkinson's disease

1064 An analysis of the relationship between muscle sympathetic nerve activity and cardiac 123I-metaiodobenzylguanidine uptake in patients with Parkinson's disease

Abnormality of the left ventricular sympathetic nervous function assessed by I-123 metaiodobenzylguanidine imaging in pediatric patients with neurocardiogenic syncope.

The purpose of this study was to assess the left ventricular sympathetic nervous system function in the patients with neurocardiogenic syncope (NCS) using I-123 metaiodobenzylguanidine (MIBG) imaging of the heart, and to compare the plasma noradrenaline (NA) and MIBG results of tilt positive and tilt negative patients following a head-up tilt test (HUT). The study included 30 patients. Their physical and laboratory examinations did not show a pathology that may be the cause of their syncope. HUT test was positive in 13 patients and negative in 17 patients. Plasma NA concentrations were higher in the HUT positive than the HUT negative group at the beginning and at the 10th minute of the test. Specific I-123 MIBG uptake assessed as the cardiac to mediastinal activity ratio in the delayed image was significantly higher in HUT positive group. The higher levels of MIBG uptake and plasma NA observed in HUT positive patients may reflect the greater capacity of NA storage in cardiac adrenergic neuronal tissue in patients with NCS. The results of this study support the critical role of autonomic nervous system in the pathophysiology of NCS and the excessive sympathetic nervous stimulation as the trigger of paradox reflex.

Onset age and severity of motor impairment are associated with reduction of myocardial 123I-MIBG uptake in Parkinson’s disease

Objectives: To elucidate the factors associated with severity of cardiac sympathetic nerve involvement in idiopathic Parkinson’s disease (PD). Methods:123I-metaiodobenzylguanidine uptake was examined in 88 patients with PD. The ratio of...

Carvedilol improves left ventricular function in heart failure patients with idiopathic dilated cardiomyopathy and a wide range of sympathetic nervous system function as measured by iodine 123 metaiodobenzylguanidine

Background. Carvedilol treatment reduces the mortality rate in patients with congestive heart failure. It is not known whether carvedilol treatment is effective in heart failure patients with substantial cardiac sympathetic nerve dysfunction. The goal of this study was to determine the effect of chronic carvedilol treatment in patients with cardiac sympathetic nerve dysfunction of varying severity. Methods and Results. In 22 congestive heart failure patients with idiopathic cardiomyopathy, sympathetic nerve function was assessed before and after 7.2 ± 2.7 months of carvedilol treatment with the use of iodine 123 metaiodobenzylguanidine (MIBG) imaging, radionuclide ventriculography, and transmyocardial norepinephrine sampling. Patients with relatively advanced impairment of cardiac sympathetic nerve function, as manifested by a baseline I-123 MIBG ratio lower than 1.40, had a statistically significant improvement in I-123 heart-mediastinum ratio with carvedilol treatment, from 1.26 ± 0.12 to 1.39 ± 0.20 ( P = .004). Of 10 patients with a baseline I-123 MIBG ratio lower than 1.40, 9 had an increase in the heart-mediastinum ratio with carvedilol treatment. Left ventricular ejection fraction increased from 25.4% ± 7.8% to 37.3% ± 14.7% ( P < .001), with no difference between patients with relatively advanced versus relatively preserved cardiac sympathetic nerve function. Conclusions. Most patients with congestive heart failure show a favorable response in left ventricular function to carvedilol treatment, regardless of the baseline level of cardiac sympathetic nervous system function, as assessed by neuronal imaging with I-123 MIBG. Patients with relatively advanced impairment of baseline I-123 MIBG uptake are most likely to show evidence of improved cardiac sympathetic nervous system function in response to carvedilol therapy. (J Nucl Cardiol 2002;9:608-15)