Metaiodobenzylguanidine Myocardial Scintigraphy Research Articles

Changes in Cardiac Denervation Independent of Changes in Systolic Function During Follow-up in CHF Patients

Introduction: Regional cardiac denervation in chronic heart failure (CHF) is associated with propensity towards arrhythmogenesis and with increased cardiac effects of catecholamines. The objectives of the study were to evaluate relationships between the extent of denervation utilising metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy and markers of LV systolic dysfunction in severe CHF patients, and to assess the progression of sympathetic nervous dysfunction. Methods: 123I-MIBG was performed in 41 CHF patients (mean LVEF 30 ± 7%) and was repeated in a subgroup of 14 patients after one year. The early and delayed heart to mediastinum ratio (EHMR and DHMR) and washout rate were calculated. Echocardiographic LVDs, LVDd and LVEF as well as NT-proBNP concentrations were determined at the same time points. Results: CHF was infarct-related in 68% of the patients. At baseline, EHMR and DHMR (1.7 ± 0.18 and 1.59 ± 0.18) were significantly lower than population norms (2.42 ± 0.27 and 2.60 ± 0.15, respectively). There was a weak inverse relationship between EHMR and LVDd (r = −0.37, p = 0.025) and LVDs (r = −0.30, p = 0.086), but not with LVEF. NT-proBNP concentrations also inversely correlated with DHMR (r = −0.33, p = 0.04). As regards the progression of myocardial denervation, there was a significant decrease in DHMR (1.55 ± 0.25 vs.1.26 ± 0.3, p = 0.0002), with no significant change in LV functional parameters or NT-pro-BNP levels. Conclusions: CHF is associated with marked myocardial sympathetic dysfunction, which is weakly correlated with LVD and NT-proBNP concentrations. Sympathetic nervous activity deteriorated significantly during 12 months follow-up, independently of changes in systolic function.

Amitriptyline and Lorazepam Improved Catatonia and Occipital Hypoperfusion in a Patient with DLB

A 76-year-old woman presented with catatonia, refusal to eat due to delusion, and visual hallucination. Single photon emission computed tomography showed remarkable occipital hypoperfusion and frontal hyperperfusion. (123)I metaiodobenzyl guanidine myocardial scintigraphy revealed decreased uptake. She was diagnosed as probable dementia with Lewy bodies (DLB). Intravenous or oral L-dopa had no effect on catatonia. Amitriptyline and lorazepam improved catatonia and visual hallucination. Cerebral blood flow of the frontal and occipital lobes seemed to be normalized. Occipital hypoperfusion is one of the features of DLB. Although the mechanism of perfusion abnormality in DLB remains to be clarified, our case suggested that it might be reversible.

Syncope and autonomic cardiovascular dysfunction in Parkinson disease

Background and purposeThe 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 methodsTwenty-four PD patients were studied, including 10 subjects with syncope/presyncope and 14 controls 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. ResultsDifferences 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 daytime minimum systolic blood pressure (95% CI: 0.78–0.98; p = 0.007) may be related to the occurrence of syncope/presyncope. ConclusionsThe 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.

Gammagrafía miocárdica con 123I-MIBG en el diagnóstico de la demencia con cuerpos de Lewy

Introduction Lewy body dementia (LBD) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). A cardiac post-ganglionic sympathetic denervation has been described in this condition which can be quantified by MIBG (metaiodobenzylguanidine) myocardial scintigraphy. The aim of our work was to retrospectively evaluate cardiac MIBG uptake (expressed as the heart-to-mediastinum ratio at 4 h (HMR) in patients with suspected LBD, and to examine its relationship with clinical and para-clinical data. Material and methods A total of 77 patients with clinical suspicion of LBD evaluated at our centre between September 2005 and June 2008 to whom a MIBG myocardial scintigraphy has been performed were retrospectively reviewed. International Consensus Criteria of LBD were applied to divide the sample into probable LBD, possible LBD and non-LBD. HMR values and their relationships with clinical and neuropsychological data were analysed. A subgroup of patients had FP-CIT (fluoropropyl-carbomethoxy-3β-4-iodophenyltropane) SPECT as a part of the evaluation. Results Mean HMR values were significantly lower in probable LBD group than in possible LBD and non-LBD groups. Low HMR values were associated only with reduced FP-CIT uptake in the striatum, but not with any clinical or neuropsychological item. Conclusions Low MIBG myocardial scintigraphy uptake is a robust measure in LBD, and it is not largely affected by medical conditions, or by the stage of the disease. In LBD reduced MIBG myocardial uptake is associated with nigrostriatal degeneration.

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

[(123)I]-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.

123I-MIBG Myocardial Scintigraphy in the Diagnosis of Lewy Body Dementia

Introduction Lewy body dementia (LBD) is the second most common cause of neurodegenerative dementia after Alzheimer's disease (AD). A cardiac post-ganglionic sympathetic denervation has been described in this condition which can be quantified by MIBG (metaiodobenzylguanidine) myocardial scintigraphy. The aim of our work was to retrospectively evaluate cardiac MIBG uptake (expressed as the heart-to-mediastinum ratio at 4h (HMR) in patients with suspected LBD, and to examine its relationship with clinical and para-clinical data. Material and methods A total of 77 patients with clinical suspicion of LBD evaluated at our centre between September 2005 and June 2008 to whom a MIBG myocardial scintigraphy has been performed were retrospectively reviewed. International Consensus Criteria of LBD were applied to divide the sample into probable LBD, possible LBD and non-LBD. HMR values and their relationships with clinical and neuropsychological data were analyzed. A subgroup of patients had FP-CIT (fluoropropyl-carbomethoxy-3β-4-iodophenyltropane) SPECTas a part of the evaluation. Results Mean HMR values were significantly lower in probable LBD group than in possible LBD and non-LBD groups. Low HMR values were associated only with reduced FP-CIT uptake in the striatum, but not with any clinical or neuropsychological item. Conclusions Low MIBG myocardial scintigraphy uptake is a robust measure in LBD, and it is not largely affected by medical conditions, or by the stage of the disease. In LBD reduced MIBG myocardial uptake is associated with nigrostriatal degeneration.

P1.190 Detection of Lewy body disease in patients with late-onset depression, anxiety and psychotic disorder with myocardial meta-iodobenzylguanidine scintigraphy

Katsuji Kobayashi, Hisashi Sumiya, Hiroyuki Nakano, Noriko Akiyama, Katsumi Urata and Yoshifumi Koshino Department of Psychiatry, Awazu Neuropsychiatric Sanatorium, 88 Yatano-machi, Komatsu-shi, Ishikawa-ken, 923-0342, Japan Department of Psychiatry and Neurobiology, Kanazawa University Graduate School of Medical Sciences, 13-1, Takara-machi, Kanazawashi, Ishikawa-ken, 920-8641, Japan Department of Nuclear Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1, Takara-machi, Kanazawa-shi, Ishikawa-ken, 920-8641, Japan Department of Nuclear Medicine, Yawata Medical Center Hospital, 12-7, Yawata, Komatsu-shi, Ishikawa-ken, 923-8551, Japan Correspondence to: Dr K. Kobayashi, E-mail: k-koba@ta2.so-net.ne.jp

Cardiac neurotransmission imaging with 123I-meta-iodobenzylguanidine in postural tachycardia syndrome

BackgroundPostural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterised by excessive tachycardia of unknown aetiology. Whether this condition involves abnormal cardiac sympathetic innervation or function remains elusive....

Predictor of underlying myocardial damage in normally functioning left ventricle with narrow QRS complex: relationship between QRS duration at right ventricle pacing and iodine-123 metaiodobenzylguanidine myocardial scintigraphy

Washout rate of iodine-123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy is correlated with the degree of myocardial damage. The aim of this study is to ascertain whether there is any relationship between QRS complex duration at right ventricle (RV) pacing and the degree of myocardial damage assessed by I-123 MIBG myocardial scintigraphy in normally functioning left ventricle. The study included 22 patients (10 men and 12 women, ranging in age from 48 to 89 years), with atrioventricular (AV) block (n = 15) and sick sinus syndrome (n = 7). All patients had baseline QRS duration of less than 120 ms and received implantation of a DDD-mode permanent pacemaker. Iodine-123 MIBG myocardial scintigraphy was performed before the pacemaker implantation, and QRS duration at RV pacing at a rate of 70 ppm was calculated immediately after the implantation. With the use of RV pacing, QRS duration was prolonged ranging from 122.4 to 185.6 ms with a mean of 153.2 +/- 15.2 ms. Washout rate of I-123 MIBG myocardial scintigraphy (WR) was calculated as ranging from 5.0 to 83.0% with a mean of 44.2 +/- 17.5%. There was a strong correlation between WR and QRS duration at RV pacing (r = 0.735, p < 0.001). It was confirmed that WR of I-123 MIBG was correlated positively with QRS duration at RV pacing. Measurement of QRS duration may be helpful to evaluate the degree of underlying myocardial damage even in the normally functioning left ventricle.

P1.22 Progression of thermal sweating dysfunction and findings on [123I]metaiodobenzylguanidine myocardial scintigraphy in Parkinson's disease patients

P1.22 Progression of thermal sweating dysfunction and findings on [123I]metaiodobenzylguanidine myocardial scintigraphy in Parkinson's disease patients

Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction

Objective: To clarify the features of pure akinesia (PA) and progressive supranuclear palsy (PSP) in the early stage of disease.Methods: We investigated 15 PA and 41 PSP patients' clinical and radiologic features including head MRI, ethyl cysteinate dimmer-single photon emission-computed tomography (ECD-SPECT) and iodine-123 meta-iodobenzyl guanidine (123I-MIBG) myocardial scintigraphy. In ECD-SPECT study, cerebral blood flow (CBF) reduction was quantitatively expressed as Z-score, and that in the frontal lobe was evaluated.Results: Many PSP patients claimed falls as the initial symptom but no PA patients did. Eye movement, as well as optokinetic nystagmus elicitation, was more frequently disturbed in PSP. Dementia, dysarthria and rigidity were also more frequent in PSP than in PA. Midbrain tegmentum atrophy in head MRI was more frequently observed in PSP. CBF in the frontal lobe, especially in the frontal eye field, was significantly lower in PSP than in PA. MIBG myocardial scintigraphy showed no difference between two groups.Discussion: PA and PSP show distinct symptoms from the early stage, indicating that they are distinct disorders. The occurrence of falls and eye movement disturbance, as well as CBF reduction at the frontal eye field, is very important for distinguishing these disorders.

Cardiac sympathetic denervation in Parkinson’s disease linked to SNCA duplication

Parkinson’s disease (PD) linked to SNCA multiplication is an autosomal dominant trait of familial PD, and is characterized by early age at onset, autonomic disturbance, and rapidly progressive dopa-responsive parkinsonism, followed by dementia [1]. Reduced cardiac uptake of meta-iodobenzylguanidine (MIBG) on MIBG myocardial scintigraphy or Xuorodopamine on positron emission tomography has been reported in patients with SNCA multiplication as well as PD [2, 4, 7, 9]. Recently, we reported a profound depletion of the cardiac sympathetic nerve in patients with Lewy bodies as in PD and dementia with Lewy bodies (DLB) but not in patients without Lewy bodies as in multiple system atrophy (MSA), progressive supranuclear palsy (PSP), PD linked to Parkin mutations, and Alzheimer disease (AD), which strongly suggests that the presence of Lewy bodies is linked to the profound depletion of the cardiac sympathetic nerve, accounting for reduced cardiac uptake of MIBG or Xuorodopamine [5, 6]. In this study, we immunohistochemically examined heart tissues from three patients with PD linked to SNCA duplication and three control subjects (aged 74.3 § 19.0 years) to determine whether the cardiac sympathetic nerve is pathologically involved. The proband (patient 1) developed parkinsonism at age 61 and died at age 70. Her uncle (patient 2), who was also her husband, developed parkinsonism at age 71 and died at age 78. Their elder son (patient 3) developed parkinsonism at age 39 and died at age 54. The clinical and neuropathological Wndings of these patients were reported by Wakabayashi [10]. Quantitative PCR analysis demonstrated that all the patients were heterozygous for SNCA duplication [3]. In each of the six subjects, blocks were taken from the anterior wall of the left ventricle and the paravertebral sympathetic ganglia as previously described [5]. A 4m thick paraYn-embedded sections were immunostained with antibodies against tyrosine hydroxylase (TH) (TH16; Sigma, St. Louis, MO), phosphorylated neuroWlament (NF) (SMI-31; Sternberger Immunochemicals, Baltimore) or phosphorylated -synuclein (#64; WAKO, Osaka, Japan), using the avidin–biotinperoxidase complex method with a Vectastain ABC kit (Vector, Burlingame, CA). In controls, numerous TH(Fig. 1a) and NF-immunoreactive (ir) (Fig. 1e) axons were seen both in the epicardial nerve fascicles and in the myocardium. However, there were no -synuclein aggregates in either the epicardial nerve fascicles (Fig. 1i) or myocardium. The number of the epicardial nerve fascicles examined of controls 1, 2, and 3 S. Orimo (&) Department of Neurology, Kanto Central Hospital, 6-25-1 Kami-Yoga, Setagaya-ku, Tokyo 158-8531, Japan e-mail: orimo@kanto-ctr-hsp.com

Transcranial sonography of the substantia nigra and MIBG myocardial scintigraphy: Complementary role in the diagnosis of Parkinson's disease

Both transcranial sonography (TCS) of the substantia nigra (SN) and metaiodobenzylguanidine (MIBG) myocardial scintigraphy have been determined to be useful for the diagnosis of Parkinson's disease (PD). In the present study, we performed both tests in 65 consecutive Japanese patients with idiopathic PD. In 30 PD patients (46.2%), the midbrain was adequately displayed by TCS allowing quantitative measurements of SN hyperechogenic areas. No significant correlation was found between the area of SN echogenicity and the reduction of myocardial uptake of MIBG. However, if the cut-off value was appropriately set, 29 patients (97%) were identified as abnormal by combined TCS and MIBG myocardial scintigraphy. Since TCS and MIBG myocardial scintigraphy can distinctively detect PD-related pathological phenomenon, it is expected that the combination of these tests could contribute to an accurate diagnosis of PD.

Effect of spinal cord stimulation on cardiac adrenergic nerve function in patients with cardiac syndrome X

In patients with cardiac syndrome X (CSX) who present with refractory angina episodes, spinal cord stimulation (SCS) has beneficial effects. The mechanisms of SCS, however, remain speculative. We assessed the effects of SCS on cardiac sympathetic function in these patients. We studied 11 CSX patients treated by SCS for refractory angina (mean age, 60 +/- 9 years; 5 men and 6 women), both during SCS therapy (SCS-ON) and after withdrawal of SCS therapy (SCS-OFF), using a randomized crossover design. Planar and single photon emission computed tomography iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy and technetium 99m sestamibi (MIBI) bicycle exercise stress testing were performed at the end of each period. Compared with 10 healthy control subjects, CSX patients showed a lower heart-mediastinum ratio for MIBG uptake (2.19 +/- 0.3 vs 1.69 +/- 0.3, P = .001) and a higher cardiac MIBG uptake score (4.0 +/- 2.5 vs 19.7 +/- 27, P = .08). There were no differences in CSX patients during the SCS-ON and SCS-OFF phases of the study in heart-mediastinum ratio (1.74 +/- 0.3 vs 1.69 +/- 0.3, P = .13), cardiac washout rate of MIBG (42.9% +/- 14% vs 43.3% +/- 14%, P = .08), or MIBG defect score (18.7 +/- 25 vs 19.7 +/- 27, P = .22). Reversible perfusion defects during the SCS-OFF phase were detected in 8 patients; an improvement in perfusion defects was observed in 2 patients (25%) during the SCS-ON phase. Our data confirm the presence of abnormal cardiac adrenergic nerve function in CSX patients. SCS was unable to result in significant improvement of cardiac MIBG uptake abnormalities, suggesting that its therapeutic effects are unlikely to be mediated by modulation of cardiac adrenergic nerve activity.

パーキンソン病およびレビー小体型認知症の早期診断法の確立とその病態機序に関する研究

[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.

Decreased cardiac uptake of MIBG is a potential biomarker for the presence of Lewy bodies

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) has been reported in patients with Parkinson's disease (PD), dementia with Lewy bodies (DLB) and pure autonomic failure (PAF). This imaging approach is a sensitive diagnostic tool that possibly differentiates PD and DLB from other movement disorders and Alzheimer's disease (AD). We recently reported cardiac sympathetic denervation in PD, DLB and PAF, which accounts for the decreased cardiac uptake of MIBG in these disorders. Patients with PD, DLB and PAF have Lewy bodies (LBs) in the nervous system, whereas patients with multiple system atrophy (MSA), progressive supranuclear palsy, corticobasal degeneration, AD and parkin-associated PD 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 decreased cardiac uptake of MIBG is a potential biomarker for the presence of LBs. We infer that MIBG myocardial scintigraphy is a non-invasive tool that allows us to detect LBs during life.

Degeneration of cardiac sympathetic nerve begins in the early disease process of Parkinson's disease.

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [(123)I] MIBG myocardial scintigraphy has been reported in the early stages of Parkinson's disease (PD), which suggests involvement of the cardiac sympathetic nerve in the early disease process of PD. For confirmation, we immunohistochemically examined cardiac tissue, sympathetic ganglia and medulla oblongata of 20 patients with incidental Lewy body disease (ILBD), which is thought to be a presymptomatic stage of PD, and 10 control subjects, using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). Immunoreactive nerve fibers of fascicles in the epicardium were well preserved in 10 of the 20 patients with ILBD and in the control subjects. In contrast, TH-immunoreactive nerve fibers had nearly disappeared in six subjects and were moderately decreased in four of the 20 patients with ILBD. Neuronal cell loss in the dorsal vagal nucleus and the sympathetic ganglia was not detectable in any of the ILBD patients examined. These findings suggest that degeneration of the cardiac sympathetic nerve begins in the early disease process of PD and that it occurs before neuronal cell loss in the dorsal vagal nucleus.

Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [(123)I] 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.

Cardiac sympathetic denervation in Lewy body disease

[ 123I] meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is a useful diagnostic tool to differentiate Parkinson's disease and dementia with Lewy bodies (Lewy body disease) from other related movement disorders, PARK2, and Alzheimer's disease. Postmortem study revealed that cardiac sympathetic denervation occurs in Lewy body disease and indicates the presence of Lewy pathology, which accounts for the decreased cardiac uptake of MIBG in Lewy body disease. Moreover, degeneration of cardiac sympathetic nerve precedes the neuronal loss in the sympathetic ganglia.

Value of 123 I-MIBG radioactivity in the differential diagnosis of DLB from AD

To evaluate the diagnostic reliability of cardiac iodine-123 metaiodobenzylguanidine ((123)I-MIBG) radioactivity in discriminating dementia with Lewy bodies (DLB) from Alzheimer disease (AD) regardless of parkinsonism. The diagnosis of DLB may be confounded by the absence of parkinsonism. This highlights the need to improve the accuracy of antemortem diagnosis of DLB without parkinsonism. Cardiac sympathetic denervation was examined using myocardial (123)I-MIBG scintigraphy in 37 patients with DLB, 42 patients with AD, and 10 normal elderly controls. The DLB patients consisted of seven patients without parkinsonism (DLB/P-) and 30 patients with parkinsonism (DLB/P+) at the time of the study. The heart-to-mediastinum uptake ratio (H/M ratio) of myocardial MIBG uptake was decreased in both the DLB groups vs the AD group (p < 0.0001) and control group (p < 0.0001). The washout rate (WR) was higher in the DLB group than in the control group (p < 0.0001) and AD group (p < 0.0001). No differences were found between the AD and control groups or between the DLB/P+ and DLB/P- groups in either the early or delayed H/M ratio or WR. In discriminating between DLB and AD, regardless of parkinsonism, the delayed H/M ratio had a sensitivity of 100%, a specificity of 100%, and a positive predictive value of 100% at a cutoff value of 1.68. Our results indicate that dementia with Lewy bodies results in cardiac sympathetic denervation and that iodine-123 metaiodobenzylguanidine myocardial scintigraphy is a sensitive tool for discriminating dementia with Lewy bodies from Alzheimer disease even in patients without parkinsonism.