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Abstract
Eur J Nucl Med Mol Imaging (2016) 43:184–192 DOI 10.1007/s00259-015-3146-y ORIGINAL ARTICLE Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer’sdisease 1 1 1 1 Soichiro Shimizu & Kentaro Hirao & Hidekazu Kanetaka & Nayuta Namioka & 1 1 1 1 Hirokuni Hatanaka & Daisuke Hirose & Raita Fukasawa & Takahiko Umahara & 1 1 Hirohumi Sakurai & Haruo Hanyu Received: 18 March 2015 /Accepted: 14 July 2015 /Published online: 2 August 2015 The Author(s) 2015. This article is published with open access at Springerlink.com Abstract significantly higher frequency of parkinsonism in the abnor- Purpose I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3- mal DAT SPECT group than the normal DAT SPECT group. fluoropropyl) nortropane ( I-FP-CIT) dopamine transporter On the other hand, there was a higher frequency of the appear- single photon emission computed tomography (DAT SPECT) ance of rapid eye movement (REM) sleep behavior disorder in and I-metaiodobenzylguanidine (MIBG) myocardial scin- the abnormal MIBG uptake group than the normal MIBG tigraphy can be used to assist in the diagnosis of patients with uptake group. dementia with Lewy bodies (DLB). We compared the diag- Conclusion These results suggested that using a combination nostic value of these two methods in differentiating DLB from of these scintigraphic methods is a useful and practical ap- Alzheimer’s disease (AD). Furthermore, we evaluated wheth- proach to differentiate DLB from AD. er a combination of DAT SPECT and MIBG myocardial scin- tigraphy would provide a more useful means of differentiating . . . Keywords I-FP-CIT DAT SPECT MIBG myocardial between DLB and AD. . . scintigraphy Alzheimer’sdisease Dementia with Lewy Methods Patients with AD (n=57) and patients with DLB bodies (n=76) who underwent both DAT SPECT and MIBG myo- cardial scintigraphy were enrolled. The sensitivity, specificity, and accuracy of both methods as well as their combination for Introduction differentiating DLB from AD were calculated. Moreover, we examined whether symptoms of the patients with DLB were Dementia with Lewy bodies (DLB) is recognized as the sec- associated with the patterns of the abnormalities displayed on ond most common cause of degenerative dementia in older DAT SPECT and MIBG myocardial scintigraphy. people, following Alzheimer’s disease (AD). In some cases, Results The sensitivity and specificity of differentiating DLB the clinical differentiation of patients with DLB from those from AD were 72.4 and 94.4 % by the heart to mediastinum with AD may be difficult because of overlapping clinical ratio of MIBG uptake, 88.2 and 88.9 % by the specific binding and pathological features. The importance of accurate identi- ratio on DAT SPECT, and 96.1 and 90.7 % by their combina- fication of patients with DLB lies particularly in its pharma- tion, respectively. The combined use of DAT SPECT and cological management, with favorable responsiveness to cho- MIBG myocardial scintigraphy enabled more accurate differ- linesterase inhibitors but severe sensitivity to the adverse ef- entiation between DLB and AD compared with either DAT fects of neuroleptic agents [1]. SPECT or MIBG myocardial scintigraphy alone. There was a The first consensus clinical diagnostic criteria for DLB that were developed [2] had high specificity for the diagnosis of * Soichiro Shimizu probable DLB, but poor sensitivity [3]. In view of these difficul- soichiro_s@hotmail.com ties the consensus criteria were revised [4], with the addition of new features to improve the diagnosis of DLB. Abnormal find- ings on dopamine transporter (DAT) imaging were considered Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan the most important among the various neuroimaging features Eur J Nucl Med Mol Imaging (2016) 43:184–192 185 listed as one of the suggestive features of DLB, whereas findings Mini-Mental State Examination (MMSE) [31] scores between from other neuroimaging techniques, including I- 14 and 26. All subjects underwent both DAT SPECTand MIBG metaiodobenzylguanidine (MIBG) myocardial scintigraphy myocardial scintigraphy. The interval between undergoing the were listed only as supportive of DLB (commonly present in two methods of imaging was less than 2 months. Of the 133 DLB but not proven to have diagnostic specificity). patients, 57 had a diagnosis of probable AD based on the Na- I-2β-Carbomethoxy-3β-(4-iodophenyl)-N-(3- tional Institute of Neurological and Communicative Disorders fluoropropyl) nortropane ( I-FP-CIT), a ligand that binds to and Stroke and Alzheimer’s Disease and Related Disorders As- the presynaptic DAT, can be used to analyze the integrity of the sociation (NINCDS-ADRDA) criteria [32] and the other 76 had nigrostriatal projection pathway. I-FP-CIT DATsingle photon a diagnosis of probable (36 patients) and possible DLB (40 emission computed tomography (SPECT) has been used in a patients) based on the consortium on DLB international work- large number of trials to identify the in vivo loss of DATs in shop criteria [4], except for low DAT uptake in the basal ganglia, the striatum of patients with presynaptic parkinsonism [5, 6]. which was also included because one of the aims of this study Previous studies showed that DAT SPECT substantially en- was to determine whether DAT SPECT is useful for the diagno- hanced the accuracy of the diagnosis of DLB compared with sis of DLB. clinical criteria alone and has a high diagnostic accuracy in dif- All patients underwent general physical, neurological, and ferentiating DLB patients from non-DLB patients [7–16]. psychiatric examinations, extensive laboratory tests, and com- On the other hand, recent studies have indicated that MIBG puted tomography (CT) or magnetic resonance imaging myocardial scintigraphy is able to detect early disturbances of (MRI) to establish a clinical diagnosis and to exclude other the sympathetic nervous system in DLB, independently of the potential causes of dementia. None of the subjects had any duration of disease and autonomic failure, and provides diagnos- history of cerebrovascular disease, other degenerative dis- tic information useful for differentiating DLB from AD [17–24]. eases, infarction in the region of the basal ganglia or intracra- The usefulness of both DAT SPECTand MIBG myocardial nial lesions on brain MRI, thyroid disease, diabetes mellitus, scintigraphy for the diagnosis of DLB has recently been sug- or previous relevant cardiac disease, nor were taking any med- gested by two meta-analysis studies [25, 26]. Moreover, the ications known to interact with the striatal binding of I-FP- utility of the combination of DAT SPECT and MIBG myocar- CIT (e.g., cocaine, amphetamines, bupropion, selective sero- dial scintigraphy was reported in patients with DLB and tonin reuptake inhibitors, etc.) [33, 34]orthataffectMIBG Parkinson syndrome (PS) [14, 15, 27–29]. Furthermore, the accumulation [35]. use of I-FP-CIT was approved by the Japanese Ministry of The Hachinski ischemic score [36] was less than 4 in all Health, Labour and Welfare in February 2014. patients. Based on the UK Parkinson’s Disease Society Brain In the present study, we performed both DAT SPECT and Bank criteria [37], parkinsonism was defined as the presence MIBG myocardial scintigraphy in patients with DLB and AD, of bradykinesia, associated with one or more of the following and compared the diagnostic value of these two methods in three features: tremor, rigidity, or postural instability. differentiating DLB from AD. We also examined whether a None of the patients with probable AD had fluctuating combination of DAT SPECT and MIBG myocardial scintig- cognition, visual hallucinations, parkinsonism, or rapid eye raphy would provide a more useful means of differentiating movement (REM) sleep behavior disorder (RBD) as deter- between DLB and AD compared with either of the two mined by three geriatric neurologists (H.H., T.U., and S.S.). methods alone. Moreover, we examined whether the particu- This study was approved by the Ethics Committee of To- lar symptoms of the DLB patients would be associated with kyo Medical University. Informed consent was obtained from the abnormalities observed on DAT SPECT and MIBG myo- all subjects (either the patients themselves or their closest rel- cardial scintigraphy. To our knowledge, this is the first study ative) before entry, following a detailed explanation of the to evaluate the diagnostic value of a combination of these two study’s aim. In accordance with the research plan, the fees of methods in differentiating DLB from AD. MIBG myocardial scintigraphy and DAT SPECTexamination for the patients with AD were paid for using the research funds of our department. All procedures were in accordance with the Materials and methods ethical standards on human investigation and with the princi- ples of the Declaration of Helsinki. Patients Image analysis A total of 133 outpatients with AD or DLB from the Memory Disorder Clinic at the Department of Geriatric Medicine, Tokyo I-MIBG myocardial scintigraphy Medical University, were enrolled in this study from March 2014 until September 2014. They had a dementia severity of 1 (mild) After the patient had rested for 15 min in the supine position, or 2 (moderate) based on the Clinical Dementia Rating [30]and 111 MBq of I-MIBG was injected intravenously. Early and 186 Eur J Nucl Med Mol Imaging (2016) 43:184–192 delayed SPECT were performed at 20 min and 4 h after the receiver-operating characteristic (ROC) analysis. For the injection, respectively. Planar imaging for 5 min in the anterior combined use of DAT SPECT and MIBG myocardial projection was performed during SPECT automatically. Pla- scintigraphy, we developed the combined DAT*MIBG nar scan and SPECT were performed with a dual-head gamma index, defined as (SBR*H/M in the delayed phase). camera equipped with a low-energy, high-resolution parallel- The cutoff values (mean−2 SD) were 1.82, 1.77, 12.38, hole collimator (PRISM 2000VP, Picker). After the scatter and 4.18 for the H/M in the early phase, the H/M in the correction, relative organ uptake was determined by setting delayed phase, washout ratio, and SBR, respectively. We the region of interest (ROI) on the anterior view [38]. The adopted the best value in ROC analysis as the cutoff heart to mediastinum (H/M) ratio was calculated by dividing value (10.18) of the DAT*MIBG index. All data were the count density of the left ventricular ROI by that of the statistically analyzed using MedCalc software (version mediastinal ROI, according to the standard method described 13.3.0.0, MedCalc Software, Mariakerke, Belgium). previously [17, 39]. The normal H/M ratios in the early phase and the delayed phase as well as the washout ratios obtained from eight normal elderly controls in our institute (three men and five women, mean age 76.5±5.8 years) were 2.56±0.37, Results 2.53±0.38, and 32.90±10.26, respectively. Values were con- sidered abnormal if they were less than 2 SDs below the con- Table 1 shows the characteristics of the patients. No signifi- trol mean. For the comparison study, H/M ratios calculated cant differences in the two groups were found in terms of age, from the ROI counts obtained by delayed SPECT were used length of education, duration of disease, and MMSE scores. for analysis, because delayed scans display the neuronal up- The number of women was significantly higher in the AD take of MIBG more explicitly [17]. group (p<0.01). Mean H/M ratios of MIBG uptake in the early phase DAT SPECT imaging and specific binding ratio analysis (3.2±0.5 vs 2.2±0.8, p<0.0001, cutoff 1.82) and delayed phase (2.9±0.6 vs 1.7±0.8, cutoff 1.77, p<0.0001, Three hours after injection of approximately 185 MBq of I- Fig. 1, left) were significantly lower and mean washout FP-CIT, projection data were obtained in a 128×128 matrix ratios (21.7±10.0 vs 38.3±10.2, cutoff 12.38, p<0.0001) on a Siemens Symbia T16 mounted with low- to medium- were significantly higher in patients with DLB than in energy general purpose (LMEGP) collimators. Projection data patients with AD. ROC analysis demonstrated that there were acquired for 28 min. Data were reconstructed by ordered was no significant difference in diagnostic accuracy subset expectation maximization (OSEM) method (iteration 8, among these three ratios. The area under the curve was subset 6) using Flash 3D software (Siemens) and corrected for 0.864 for the delayed phase, 0.859 for the washout ratio, attenuation by CT. The specific binding ratio (SBR) was semi- and 0.835 for the early phase. quantitatively calculated using DAT VIEW software (Nihon Mean SBRs on DAT SPECT were markedly lower in pa- Medi-Physics, Tokyo, Japan) based on Bolt’s method, as de- tients with DLB than in those with AD (5.2±1.0 vs 2.7±1.3, scribed in detail elsewhere [40]. For this study, we used SBR cutoff 4.18, p<0.0001, Fig. 1, middle). Mean values of the as the mean value of the right and left SBRs. The control DAT*MIBG index (described in the “Materials and methods” group for DAT SPECT consisted of 18 subjects without any section) were significantly lower in patients with DLB than in present or previous neurological disease (7 men and 11 wom- those with AD (15.3±4.5 vs 4.6±3.0, cutoff 10.18, p<0.0001, en, mean age 78.6±6.5 years). The mean SBR of the controls Fig. 1, right). The sensitivity and specificity in differentiating was 5.84±0.83. Values were considered abnormal if they were DLB from AD were 72.4 and 94.4 % by the H/M ratio of less than 2 SDs below the control mean. MIBG uptake in the delayed phase, 88.2 and 88.9 % by the Statistical analysis Table 1 Characteristics of the patients AD (n=57) DLB (n=76) Values were expressed as means±SD and analyzed by Student’s t test, χ test, and one-way analysis of vari- Age (years) 81.4±6.1 80.2±4.9 ance. A p value of less than 0.05 was considered to Sex (male/female) 10/47* 42/34 indicate a statistically significant difference between the Length of education (years) 10.3±3.2 11.8±2.8 two groups. The sensitivity and specificity of the respec- Duration of disease (years) 2.8±1.2 3.2±0.9 tive diagnostic index (H/M ratios of MIBG uptake in the MMSE score 22.5±5.4 22.4±4.8 delayed phase, SBR on DAT SPECT, and combined DAT SPECT and MIBG myocardial scintigraphy) for the dif- MMSE Mini-Mental State Examination *p <0.01 ferentiation between DLB and AD were assessed using Eur J Nucl Med Mol Imaging (2016) 43:184–192 187 Fig. 1 Scatter plots of the H/M MIBG DAT-SPECT DAT-SPECT*MIBG ratio on MIBG myocardial p < 0.0001 scintigraphy in the delayed phase p < 0.0001 p < 0.0001 (left), SBR on DAT SPECT SBR SBR*H/M H/M (middle), and DAT*MIBG index (right) in patients with DLB and AD. Cutoff lines were set at 1.77 (2 SDs below the control, right), 4.18 (2 SDs below the control, middle) and 10.18 (the best value in ROC analysis, left) DLB AD AD DLB AD DLB SBR on DAT SPECT, and 96.1 and 90.7 % by the Forty-six patients showed reduced tracer uptake on both DAT*MIBG index, respectively. DAT SPECT and MIBG myocardial scintigraphy (Fig. 3, The area under the curve was 0.864 for the H/M ratio of top). Twenty-one patients showed decreased DAT uptake MIBG myocardial scintigraphy in the delayed phase, 0.923 but normal MIBG uptake (Fig. 3,middle).Ninepatients for DAT SPECT, and 0.981 for the combined use of these two showed normal DAT uptake and decreased MIBG uptake methods (Fig. 2). The combined use of the two methods en- (Fig. 3,bottom). abled more accurate differentiation of DLB from AD than either DAT SPECT or MIBG myocardial scintigraphy alone (DAT SPECT vs MIBG, p=0.170; DAT SPECTand MIBG vs MIBG, p<0.001; DAT SPECT and MIBG vs DAT SPECT, Group 1 p=0.012). Patients with DLB were categorized into three differ- ent groups by the combined use of DAT SPECT and MIBG myocardial scintigraphy. Figure 3 shows represen- H/M ratio=0.88 SBR:1.05(R:1.05, L:1.06) tative DAT SPECT and MIBG myocardial scintigraphy images of patients from the three different groups. Group 2 SBR:0.93(R:0.84, L:1.02) H/M ratio=2.74 MIBG AUC=0.864 Group 3 DAT-SPECT AUC=0.923 DAT× MIBG AUC=0.981 SBR:5.57(R:5.40, L:5.74) H/M ratio=1.24 Fig. 3 Example images of DAT SPECT and MIBG myocardial scintigraphy of patients with DLB. Group 1: low uptakes on both DAT SPECT and MIBG myocardial scintigraphy (top). Group 2: low uptake Fig. 2 ROC curves to differentiate DLB from AD. The combination of on DAT SPECT and normal on MIBG myocardial scintigraphy (middle). DAT SPECT and MIBG myocardial scintigraphy enabled more accurate Group 3: normal on DAT SPECT and low uptake on MIBG myocardial differentiation between DLB and AD. AUC area under the curve scintigraphy (bottom) 188 Eur J Nucl Med Mol Imaging (2016) 43:184–192 Table 2 shows a summary of the symptoms observed in 93.6 % for the differentiation of DLB from non-DLB using patients with DLB in the three groups. The appearance of DAT SPECT [26]. In our present study, the sensitivity and parkinsonism was significantly more frequent in patients from specificity of differentiating DLB from AD by DAT SPECT groups 1 and 2 that had abnormal DAT SPECT data, com- were 88.2 and 88.9 %, respectively, which were consistent pared with patients from group 3 that had normal DAT SPECT with the results of previous studies (sensitivities of 80 % and data (group 1 vs group 3: p<0.001; group 2 vs group 3: specificities of 90–94 %) [7–9]. p<0.001). On the other hand, the appearance of RBD in pa- In DLB, the loss of dopaminergic cells is accompanied tients of groups 1 and 3 that had abnormal MIBG uptake was by the loss of DATs (presynaptic receptors). A previous significantly more frequent compared with patients from in vitro study suggested that the loss of DAT and the loss group 2 that had normal MIBG uptake (group 1 vs group 2: of striatal dopamine content are linearly correlated [42]. Our p<0.01; group 3 vs group 2: p<0.05). result showing the significantly frequent appearance of par- kinsonism in patients with DLB who showed abnormalities on DAT SPECT was consistent with this previous in vitro study. In patients with PD, the severity of motor symptoms Discussion often correlates inversely with DAT density [43, 44]. How- ever, this association may be different in patients with DLB. In agreement with previous studies [7–26], we confirmed that Previous studies did not identify an association between the a reduction in both striatal DAT uptake and cardiac MIBG severity of parkinsonism and striatal DAT uptake in DLB uptake are characteristic features of DLB, and the combined patients [12, 45]. These results were consistent with our use of DAT SPECT and MIBG myocardial scintigraphy was results, in which no significant difference in Hoehn and Yahr more useful for differentiating DLB from AD, compared with score was observed between patients with DLB who had either of these two methods alone. Moreover, we found the low DAT uptake and those who had normal DAT uptake. presence of parkinsonism at a significantly higher frequency There appears to be a difference in DAT uptake in the basal in patients with DLB who had low DAT uptake. On the other ganglia between PD and DLB patients. Previous studies [12, hand, RBD was frequently observed in patients with DLB 46] showed that patients with DLB had significantly lower who showed abnormalities on MIBG myocardial DAT uptake mainly in the caudate nucleus. On the other scintigraphy. hand, patients with PD had significantly lower DAT uptake, Previous studies in which neuropathological autopsy was mainly in the putamen. Thus, these results suggested that performed [10, 41] suggested that DAT imaging assists in the basal ganglia pathology might differ between DLB and diagnosis of patients with DLB. A recent meta-analysis study PD. Furthermore, in patients with DLB, multifactorial pa- thology may affect the nigrostriatal connection without reported a pooled sensitivity of 86.5 % and a specificity of Table 2 DAT SPECT and MIBG myocardial scintigraphy in patients with DLB Group 1 Group 2 Group 3 Low DAT uptake, low MIBG uptake Low DAT uptake, normal MIBG uptake Normal DAT uptake, low MIBG uptake Total (n)46 21 9 Age (mean ± SD) 80.2±5.4 80.3±4.2 79.6 ± 4.6 Sex (male/female) 26/20 11/10 5/4 Prob./poss. 28 (61 %)/18 (39 %) 6 (29 %)/15 (71 %) 2 (22 %)/7 (78 %) SBR on DAT SPECT 2.29±1.03### 2.48±0.88### 5.38±0.58 H/M of MIBG 1.25±0.20*** # 2.86±0.61### 1.47±0.21 MMSE 23.2±4.3 21.0±5.1 21.9±6.0 Hoehn and Yahr score 2.2±0.9 2.2±1.2 1.0±1.4 Parkinsonism, n (%) 38 (83 %)### 18 (86 %)### 2 (22 %) Hallucination, n (%) 21 (46 %) 5 (24 %) 3 (33 %) Fluctuation, n (%) 11 (24 %) 3 (14 %) 2 (22 %) RBD, n (%) 23 (50 %)** 2 (10 %)# 4 (44 %) MMSE Mini-Mental State Examination *p<0.05; **p< 0.01; ***p< 0.001 (vs low DAT uptake/normal MIBG uptake) #p <0.05; ##p< 0.01; ###p<0.001 (vs normal DAT uptake/low MIBG uptake) Diagnosed as having DLB, as described in the manuscript Eur J Nucl Med Mol Imaging (2016) 43:184–192 189 affecting DAT binding. This was observed in a study by Liu reported that the reduction in MIBG uptake did not signifi- et al., in which parkinsonism was induced by the deposition cantly differ between patients with idiopathic RBD and DLB. of tangles in the basal ganglia [47]. The results of these studies using MIBG myocardial scintig- Many studies reported the coexistence of DLB and AD raphy, including our results, suggested a strong association pathologies. Most patients with DLB also demonstrate AD between RBD and DLB in Lewy body disease. pathology, including cortical amyloid plaques and neurofibril- IPrevious studies [14, 15, 27–29] showed that the com- lary tangles [4, 48, 49]. On the other hand, a study by the bined use of DAT SPECT and MIBG myocardial scintigra- Alzheimer’s Disease Neuroimaging Initiative reported that phy improved the diagnostic accuracy for PS and DLB. 45.5 % of patients with a diagnosis of AD before death also Camacho et al. showed that there was a positive association had DLB pathology [50]. O’Brien et al. reported that 63 % of between the results of DAT SPECT and those of MIBG patients whose diagnosis had changed from possible DLB at myocardial scintigraphy. Moreover, a close association be- baseline to probable DLB at follow-up demonstrated abnor- tween DAT SPECT and the presence of parkinsonism was malities on DAT imaging [11]. In our study, three patients with also found [14], which is consistent with our present study. AD had abnormal DAT uptake. Particularly for our present One study reported that both DAT SPECT and MIBG myo- study, to determine whether DAT SPECT is useful for the cardial scintigraphy showed high diagnostic accuracy (90 %) diagnosis of DLB, we only used the clinical signs from the to differentiate DLB from the other dementias [15]. consortium on DLB international workshop criteria [4] for the Novellino et al. reported that the combined use of both diagnosis of DLB. Based on strict diagnostic criteria, these DAT SPECT and MIBG myocardial scintigraphy in patients three patients were considered as possible DLB. Therefore, with mixed tremors and additional extrapyramidal symptoms for these three patients, careful follow-up and observation of can help differentiate patients with essential tremor from the appearance of characteristic clinical signs of DLB are those with PD and parkinsonism [28]. Kim et al. reported necessary. that the combined use of these techniques can predict the In our study, the sensitivity and specificity in differentiating prognosis of patients with drug-induced parkinsonism [29]. DLB from AD using the H/M ratio of MIBG uptake were 72.4 These two studies suggested that the combined use of DAT and 94.4 %, respectively. Various studies have reported the SPECT and MIBG myocardial scintigraphy is useful for the diagnostic accuracy of MIBG myocardial scintigraphy. Sev- diagnosis of Lewy body disease, which is usually difficult. eral single-center studies [17–23] have demonstrated lower We categorized patients with DLB into three different myocardial MIBG uptake in patients with DLB than in pa- groups from the results of both DAT SPECT and MIBG tients with the other dementias, with high sensitivity and spec- myocardial scintigraphy. Approximately 40 % of the patients ificity (both were approximately 90 %). The usefulness of displayed abnormalities on either DAT SPECT or MIBG MIBG myocardial scintigraphy in the diagnosis of DLB was myocardial scintigraphy. Moreover, parkinsonism was found recently suggested by a meta-analysis study [25]. In this study, at a significantly higher frequency in patients with DLB who MIBG myocardial scintigraphy demonstrated a high pooled had low DAT uptake than in those who had normal DAT sensitivity (98 %) and specificity (94 %) in the differential uptake. On the other hand, RBD was frequently observed in diagnosis of DLB and the other dementias. However, a recent patients with DLB who displayed abnormalities on MIBG multicenter study in Japan [24] reported a sensitivity of myocardial scintigraphy. Patients displaying low uptake on 68.9 % and a specificity of 87.0 % in all patients, which was both DAT SPECT and MIBG myocardial scintigraphy dem- consistent with our study. Moreover, this study reported that onstrated typical clinical symptoms, suggesting an associa- the sensitivity and specificity in university hospitals were 91.1 tion between abnormalities on DAT SPECT or MIBG myo- and 84.8 %, respectively. The variation in these results might cardial scintigraphy and clinical symptoms. Furthermore, the be a result of selection bias. More typical DLB patients might combined use of DAT SPECT and MIBG myocardial scin- have been enrolled in the single-center studies. Moreover, the tigraphy was suggested to enable the detection of patients fact that the mean age of patients with DLB in our study was with abnormalities on only either of the methods. However, 80.2 years, which is higher than that of the other studies, may we would like to note that for patients in whom either DAT also be a reason, because myocardial MIBG uptake is known SPECT or MIBG myocardial scintigraphy cannot be per- to significantly decrease with age [51]. formed (e.g., DAT: patients with an infarction in the basal In our study, the patients with DLB who showed abnormal- ganglia, patients who are unable to stop the use of medica- ities on MIBG myocardial scintigraphy had a significantly tions that affect DAT uptake, etc.; MIBG: patients with heart higher frequency of RBD. Miyamoto et al. reported markedly disease or diabetes mellitus, or patients taking medications reduced MIBG uptake in patients with idiopathic RBD, PD, that affect MIBG uptake, etc.), the other method can be and DLB [52, 53]. On the other hand, a more profound reduc- used. Our results showed that there was no significant dif- tion in cardiac MIBG uptake was reported in patients with ference between DAT SPECT and MIBG myocardial scin- DLB compared with patients with PD [54]. One study [53] tigraphy (p=0.170) in diagnostic accuracy evaluated by 190 Eur J Nucl Med Mol Imaging (2016) 43:184–192 ROC analysis. Moreover, when there is difficulty in diag- References nosing the patient after performing either of these methods, it is suggested that the other method should be performed. 1. McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen- Mansfield J, et al. Dementia with Lewy bodies. Lancet Neurol This study has several critical limitations. Firstly, this study 2004;3:19–28. was carried out in a single memory disorder clinic; therefore, the 2. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, number of patients enrolled in each treatment group was relative- Hansen LA, et al. Consensus guidelines for the clinical and patho- ly small. Secondly, to determine whether DAT SPECT is useful logic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47: for the diagnosis of DLB, we used the consortium on DLB 1113–24. international workshop criteria [4] as well as low DAT uptake 3. Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, et al. in the basal ganglia. However, there appeared to be no problems Movement Disorders Society Scientific Issues Committee report: in using these criteria, as all patients with DLB in this study were SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 2003;18:467–86. doi:10. probable DLB patients based on the strict DLB international 1002/mds.10459. workshop criteria [4]. Thirdly, the DAT*MIBG index is an orig- 4. McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman inal index that we devised for this study. Statistical weighting was H, et al. Diagnosis and management of dementia with Lewy bodies: not taken into account when setting this index. Therefore, further third report of the DLB Consortium. Neurology 2005;65:1863–72. doi:10.1212/01.wnl.0000187889.17253.b1. studies are necessary to examine the validity of the DAT*MIBG 5. Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van index. A potential limitation of the present study is the lack of Royen E, et al. Accurate differentiation of parkinsonism and essen- autopsy confirmation in all cases. We carefully applied rigorous tial tremor using visual assessment of [123I]-FP-CIT SPECT imag- standardized sets of diagnostic criteria, all of which have been ing: the [123I]-FP-CIT study group. Mov Disord 2000;15:503–10. 6. Booij J, Speelman JD, Horstink MW, Wolters EC. The clinical shown to have a positive predictive value of greater than 80 % benefit of imaging striatal dopamine transporters with [123I]FP- when judged by postmortem diagnosis [55, 56]. Further large CIT SPET in differentiating patients with presynaptic parkinsonism multicenter studies, with consideration of the results of patholog- from those with other forms of parkinsonism. Eur J Nucl Med ical examination, are required to confirm our results. 2001;28:266–72. In conclusion, a combination of DAT SPECT and MIBG 7. Walker Z, Costa DC, Walker RW, Shaw K, Gacinovic S, Stevens T, et al. Differentiation of dementia with Lewy bodies from myocardial scintigraphy improved the sensitivity of the detec- Alzheimer’s disease using a dopaminergic presynaptic ligand. J tion of patients with DLB. In particular, this method may pro- Neurol Neurosurg Psychiatry 2002;73:134–40. vide a powerful differential diagnostic tool when it is difficult 8. McKeith I, O’Brien J, Walker Z, Tatsch K, Booij J, Darcourt J, et al. to differentiate patients with DLB from those with AD using Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, either DAT SPECT or MIBG myocardial scintigraphy alone. multicentre study. Lancet Neurol 2007;6:305–13. doi:10.1016/ S1474-4422(07)70057-1. 9. O’Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn Acknowledgments We thank H. Hirose of the Department of Nuclear D, et al. Dopamine transporter loss visualized with FP-CIT SPECT Medicine of Tokyo Medical University for his support and technical in the differential diagnosis of dementia with Lewy bodies. Arch assistance. We are also grateful to the medical editors of the Department Neurol 2004;61:919–25. doi:10.1001/archneur.61.6.919. of International Medical Communications of Tokyo Medical University for reviewing the manuscript. 10. Walker Z, Jaros E, Walker RW, Lee L, Costa DC, Livingston G, et al. Dementia with Lewy bodies: a comparison of clinical diagno- sis, FP-CIT single photon emission computed tomography imaging Compliance with ethical standards All procedures were in accor- and autopsy. J Neurol Neurosurg Psychiatry 2007;78:1176–81. doi: dance with the ethical standards on human investigation and with the 10.1136/jnnp.2006.110122. principles of the Declaration of Helsinki. 11. O’Brien JT, McKeith IG, Walker Z, Tatsch K, Booij J, Darcourt J, et al. Diagnostic accuracy of 123I-FP-CIT SPECT in possible de- Conflicts of interest None. mentia with Lewy bodies. Br J Psychiatry 2009;194:34–9. doi:10. 1192/bjp.bp.108.052050. Ethical approval All procedures performed in studies involving hu- 12. Walker Z, Costa DC, Walker RW, Lee L, Livingston G, Jaros E, man participants were in accordance with the ethical standards of the et al. Striatal dopamine transporter in dementia with Lewy bodies institutional and/or national research committee and with the 1964 Dec- and Parkinson disease: a comparison. Neurology 2004;62:1568– laration of Helsinki and its later amendments or comparable ethical standards. 13. Morgan S, Kemp P, Booij J, Costa DC, Padayachee S, Lee L, et al. Differentiation of frontotemporal dementia from dementia with Lewy bodies using FP-CIT SPECT. J Neurol Neurosurg Informed consent Informed consent was obtained from all individual Psychiatry 2012;83:1063–70. doi:10.1136/jnnp-2012-302577. participants included in the study. 14. Camacho V, Marquié M, Lleó A, Alvés L, Artigas C, Flotats A, et al. Cardiac sympathetic impairment parallels nigrostriatal degen- Open Access This article is distributed under the terms of the Creative eration in probable dementia with Lewy bodies. Q J Nucl Med Mol Commons Attribution 4.0 International License (http:// Imaging 2011;55:476–83. creativecommons.org/licenses/by/4.0/), which permits unrestricted use, 15. Treglia G, Cason E, Cortelli P, Gabellini A, Liguori R, Bagnato A, distribution, and reproduction in any medium, provided you give appro- et al. Iodine-123 metaiodobenzylguanidine scintigraphy and iodine- priate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 123 ioflupane single photon emission computed tomography in Eur J Nucl Med Mol Imaging (2016) 43:184–192 191 Lewy body diseases: complementary or alternative techniques? J a 2-year follow-up study. Arch Gerontol Geriatr 2013;56:124–8. doi:10.1016/j.archger.2012.05.001. Neuroimaging 2014;24:149–54. doi:10.1111/j.1552-6569.2012. 00774.x. 30. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL. A new 16. Spehl TS, Frings L, Hellwig S, Weiller C, Hüll M, Meyer PT, et al. clinical scale for the staging of dementia. Br J Psychiatry 1982;140: Role of semiquantitative assessment of regional binding potential in 566–72. 123I-FP-CIT SPECT for the differentiation of frontotemporal de- 31. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. a prac- mentia, dementia with Lewy bodies, and Alzheimer’s dementia. tical method for grading the cognitive state of patients for the clini- Clin Nucl Med 2015;40:e27 –33. doi:10.1097/RLU. cian. J Psychiatr Res 1975;12:189–98. 32. McKhann G, Drachman D, Folstein M, Katzman R, Price D, 17. Yoshita M, Taki J, Yamada M. A clinical role for [(123)I]MIBG Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of myocardial scintigraphy in the distinction between dementia of the the NINCDS-ADRDA Work Group under the auspices of Alzheimer’s-type and dementia with Lewy bodies. J Neurol Department of Health and Human Services Task Force on Neurosurg Psychiatry 2001;71:583–8. Alzheimer’s Disease. Neurology 1984;34:939–44. 18. Watanabe H,Ieda T,KatayamaT,Takeda A,AibaI, DoyuM, etal. 33. Booij J, Kemp P. Dopamine transporter imaging with [(123)I]FP- Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake in de- CIT SPECT: potential effects of drugs. Eur J Nucl Med Mol mentia with Lewy bodies: comparison with Alzheimer’sdisease. J Imaging 2008;35:424–38. doi:10.1007/s00259-007-0621-0. Neurol Neurosurg Psychiatry 2001;70:781–3. 34. Djang DS, Janssen MJ, Bohnen N, Booij J, Henderson TA, Herholz 19. Oide T, Tokuda T, Momose M, Oguchi K, Nakamura A, Ohara S, K, et al. SNM practice guideline for dopamine transporter imaging et al. Usefulness of [123I]metaiodobenzylguanidine ([123I]MIBG) with 123I-ioflupane SPECT 1.0. J Nucl Med 2012;53:154–63. doi: myocardial scintigraphy in differentiating between Alzheimer’sdis- 10.2967/jnumed.111.100784. ease and dementia with Lewy bodies. Intern Med 2003;42:686–90. 35. Solanki KK, Bomanji J, Moyes J, Mather SJ, Trainer PJ, Britton 20. Hanyu H, Shimizu S, Hirao K, Kanetaka H, Iwamoto T, Chikamori KE. A pharmacological guide to medicines which interfere with the T, et al. Comparative value of brain perfusion SPECT and biodistribution of radiolabelled meta-iodobenzylguanidine [(123)I]MIBG myocardial scintigraphy in distinguishing between (MIBG). Nucl Med Commun 1992;13:513–21. dementia with Lewy bodies and Alzheimer’sdisease.Eur JNucl 36. Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Med Mol Imaging 2006;33:248–53. doi:10.1007/s00259-005- Marshall J, et al. Cerebral blood flow in dementia. Arch Neurol 1921-x. 1975;32:632–7. 21. Wada-Isoe K, Kitayama M, Nakaso K, Nakashima K. Diagnostic 37. Daniel SE, Lees AJ. Parkinson’s Disease Society Brain Bank, markers for diagnosing dementia with Lewy bodies: CSF and London: overview and research. J Neural Transm Suppl 1993;39: MIBG cardiac scintigraphy study. J Neurol Sci 2007;260:33–7. 165–72. doi:10.1016/j.jns.2007.03.016. 38. Kobayashi H, Momose M, Kanaya S, Kondo C, Kusakabe K, 22. Estorch M, Camacho V, Paredes P, Rivera E, Rodríguez-Revuelto Mitsuhashi N. Scatter correction by two-window method standard- A, Flotats A, et al. Cardiac (123)I-metaiodobenzylguanidine imag- izes cardiac I-123 MIBG uptake in various gamma camera systems. ing allows early identification of dementia with Lewy bodies during Ann Nucl Med 2003;17:309–13. life. Eur J Nucl Med Mol Imaging 2008;35:1636–41. doi:10.1007/ 39. Braune S, Reinhardt M, Schnitzer R, Riedel A, Lücking CH. s00259-008-0828-8. Cardiac uptake of [123I]MIBG separates Parkinson’s disease from 23. Noguchi-Shinohara M, Tokuda T, Yoshita M, Kasai T, Ono K, multiple system atrophy. Neurology 1999;53:1020–5. Nakagawa M, et al. CSF alpha-synuclein levels in dementia with 40. Tossici-Bolt L, Hoffmann SM, Kemp PM, Mehta RL, Fleming JS. Lewy bodies and Alzheimer’s disease. Brain Res 2009;1251:1–6. Quantification of [123I]FP-CIT SPECT brain images: an accurate doi:10.1016/j.brainres.2008.11.055. technique for measurement of the specific binding ratio. Eur J Nucl 24. Mitsuhiro Y, Miharu S, Heii A, Hiroyuki A, Eizo I, Takashi A, et al. Med Mol Imaging 2006;33:1491–9. doi:10.1007/s00259-006- Diagnostic accuracy of cardiac sympathetic imaging with 123I- 0155-x. MIBG myocardial scintigraphy in dementia with Lewy bodies: a 41. Costa DC, Walker Z, Walker RW, Fontes FR. Dementia with Lewy multicenter study. PLoS One 2015;10(3):e0120540. doi:10.1371/ bodies versus Alzheimer’s disease: role of dopamine transporter journal.pone.0120540. imaging. Mov Disord 2003;18 Suppl 7:S34–8. doi:10.1002/mds. 25. Treglia G, Cason E. Diagnostic performance of myocardial inner- vation imaging using MIBG scintigraphy in differential diagnosis 42. Bezard E, Dovero S, Prunier C, Ravenscroft P, Chalon S, Guilloteau between dementia with lewy bodies and other dementias: a system- D, et al. Relationship between the appearance of symptoms and the atic review and a meta-analysis. J Neuroimaging 2012;22:111–7. level of nigrostriatal degeneration in a progressive 1-methyl-4-phe- doi:10.1111/j.1552-6569.2010.00532.x. nyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of 26. Papathanasiou ND, Boutsiadis A, Dickson J, Bomanji JB. Parkinson’s disease. J Neurosci 2001;21:6853–61. Diagnostic accuracy of 123I-FP-CIT (DaTSCAN) in dementia with 43. Benamer HT, Patterson J, Wyper DJ, Hadley DM, Macphee GJ, Lewy bodies: a meta-analysis of published studies. Parkinsonism Grosset DG. Correlation of Parkinson’s disease severity and dura- Relat Disord 2012;18:225–9. doi:10.1016/j.parkreldis.2011.09. tion with 123I-FP-CIT SPECT striatal uptake. Mov Disord 2000;15:692–8. 27. Spiegel J, Möllers MO, Jost WH, Fuss G, Samnick S, Dillmann U, 44. Morrish PK. How valid is dopamine transporter imaging as a sur- et al. FP-CIT and MIBG scintigraphy in early Parkinson’s disease. rogate marker in research trials in Parkinson’sdisease?Mov Disord Mov Disord 2005;20:552–61 . doi:10.1002/mds.20369. 2003;18 Suppl 7:S63–70. doi:10.1002/mds.10581. 28. Novellino F, Arabia G, Bagnato A, Cascini GL, Salsone M, 45. Ziebell M, Andersen BB, Pinborg LH, Knudsen GM, Stokholm J, Nicoletti G, et al. Combined use of DAT-SPECT and cardiac Thomsen G, et al. Striatal dopamine transporter binding does not MIBG scintigraphy in mixed tremors. Mov Disord 2009;24: 2242–8. doi:10.1002/mds.22771. correlate with clinical severity in dementia with Lewy bodies. J Nucl Med 2013;54:1072–6. doi:10.2967/jnumed.112.114025. 29. Kim JS, Oh YS, Kim YI, Yang DW, Chung YA, You IR, et al. Combined use of 123I-metaiodobenzylguanidine (MIBG) scintig- 46. Ziebell M, Andersen BB, Thomsen G, Pinborg LH, Karlsborg M, raphy and dopamine transporter (DAT) positron emission tomogra- Hasselbalch SG, et al. Predictive value of dopamine transporter phy (PET) predicts prognosis in drug-induced parkinsonism (DIP): SPECT imaging with [123I]PE2I in patients with subtle 192 Eur J Nucl Med Mol Imaging (2016) 43:184–192 parkinsonian symptoms. Eur J Nucl Med Mol Imaging 2012;39: 52. Miyamoto T, Miyamoto M, Inoue Y, Usui Y, Suzuki K, Hirata K. Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep 242–50. doi:10.1007/s00259-011-1976-9. 47. Liu Y, Stern Y, Chun MR, Jacobs DM, Yau P, Goldman JE. behavior disorder. Neurology 2006;67:2236–8. doi:10.1212/01. Pathological correlates of extrapyramidal signs in Alzheimer’sdis- wnl.0000249313.25627.2e. ease. Ann Neurol 1997;41:368–74. doi:10.1002/ana.410410312. 53. Miyamoto T, Miyamoto M, Suzuki K, Nishibayashi M, Iwanami 48. Aarsland D, Perry R, Brown A, Larsen JP, Ballard C. M, Hirata K. 123I-MIBG cardiac scintigraphy provides clues to the Neuropathology of dementia in Parkinson’s disease: a prospective, underlying neurodegenerative disorder in idiopathic REM sleep community-based study. Ann Neurol 2005;58:773–6. doi:10.1002/ behavior disorder. Sleep 2008;31:717–23. ana.20635. 54. Suzuki M, Kurita A, Hashimoto M, Fukumitsu N, Abo M, Ito Y, 49. Ballard C, Ziabreva I, Perry R, Larsen JP, O’Brien J, McKeith I, et al. Impaired myocardial 123I-metaiodobenzylguanidine uptake et al. Differences in neuropathologic characteristics across the Lewy in Lewy body disease: comparison between dementia with Lewy body dementia spectrum. Neurology 2006;67:1931–4. doi:10. bodies and Parkinson’s disease. J Neurol Sci 2006;240:15–9. doi: 1212/01.wnl.0000249130.63615.cc. 10.1016/j.jns.2005.08.011. 50. Toledo JB, Cairns NJ, Da X, Chen K, Carter D, Fleisher A, et al. 55. Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom Clinical and multimodal biomarker correlates of ADNI neuropath- J, Relkin N, et al. Practice parameter: diagnosis of dementia (an ological findings. Acta Neuropathol Commun 2013;1:65. doi:10. evidence-based review). Report of the Quality Standards 1186/2051-5960-1-65. Subcommittee of the American Academy of Neurology. 51. Sakata K, Iida K, Mochizuki N, Ito M, Nakaya Y. Physiological Neurology 2001;56:1143–53. changes in human cardiac sympathetic innervation and activity 56. McKeith IG, Ballard CG, Perry RH, Ince PG, O’Brien JT, Neill D, assessed by (123)I-metaiodobenzylguanidine (MIGB) imaging. et al. Prospective validation of consensus criteria for the diagnosis Circ J 2009;73:310–5. of dementia with Lewy bodies. Neurology 2000;54:1050–8.
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European Journal of Nuclear Medicine and Molecular Imaging – Unpaywall
Published: Aug 2, 2015