123I-metaiodobenzylguanidine Uptake Research Articles

Clinical characteristics of patients with Parkinson's disease with reduced 123I-metaiodobenzylguanidine uptake in the major salivary glands and heart

BackgroundParkinson's disease (PD) shows cardiac sympathetic denervation (SD) in 123I-metaiodobezylguanidine (MIBG) scintigraphy. Recently, SD in the major salivary glands (MSG-SD) was introduced as a possible radiological feature of PD. ObjectiveTo identify the clinical characteristics of patients with PD with reduced MSG and cardiac MIBG uptake (dual-SD) compared with those with reduced MSG or cardiac MIBG uptake only (single-SD). MethodsWe recruited 90 patients with PD and 30 controls and evaluated their non-motor (e.g., hyposmia, autonomic dysfunction) and motor (e.g., Movement Disorder Society-Unified Parkinson's Disease Rating Scale) features. We also assessed MIBG uptake in the MSG and heart using a quantitative semi-automatic method, and compared MIBG uptakes between PD and controls. We set cut-off values for optimal sensitivity and specificity, and compared the clinical characteristics of patients with PD between dual- and single-SD groups. ResultsMSG and cardiac MIBG uptakes were significantly reduced in PD. Sixty-one patients had dual-SD, 25 had single-SD, and four had non-SD. In patients with PD with normal cardiac SD, 76.5% (13/17) of whom showed abnormalities only in MSG-SD. When clinical characteristics were compared between the dual-SD and single−/non-SD groups, patients in the dual-SD group were older and had more severe hyposmia and autonomic dysfunction, except motor features. Multiple logistic regression analysis identified age as an important confounder. ConclusionsPatients with PD with dual-SD have more severe non-motor features than other patients. Autonomic dysfunction might progress independently from dopaminergic degeneration. Furthermore, our findings indicate that aging is a crucial factor in PD progression.

Power spectral analysis of heart rate variability is useful as a screening tool for detecting sympathetic and parasympathetic nervous dysfunctions in Parkinson’s disease

BackgroundParkinson’s disease (PD) is a progressive neurodegenerative disorder that causes motor symptoms and autonomic dysfunction. However, autonomic function tests commonly performed in PD can only evaluate either the sympathetic or parasympathetic nervous system. Therefore, the purpose of this pilot study is to investigate whether power spectral analysis of heart rate variability could detect both sympathetic and parasympathetic nervous dysfunctions in patients with PD.MethodsSeventeen patients with PD and 11 healthy control subjects underwent electrocardiogram recording for the spectral analysis of heart rate variability to obtain values of low-frequency (LF) (0.04–0.15 Hz) and high-frequency (HF) (0.15–0.4 Hz) powers. Moreover, we examined the coefficient of variation of R–R intervals (CVRR) as a parameter of parasympathetic function in all participants and performed 123I-metaiodobenzylguanidine scintigraphy to measure the heart-to-mediastinum ratio as a parameter of cardiac sympathetic innervation in patients with PD.ResultsThe median age of control subjects and PD patients was 63 and 66 years old, respectively. The median Hoehn and Yahr scale of PD patients was stage 2. The values of resting LF and HF powers widely varied. The median values of resting LF powers of control subjects and PD patients and those of HF powers were 169 and 70 ms2, 279 and 65 ms2, respectively, the difference was statistically insignificant. Approximately 41% of patients with PD had values below the first quartile of resting LF powers (< 58 ms2) or HF powers (< 50 ms2); however, no control subject had such low values. Positive correlations were found between resting LF powers and heart-to-mediastinum ratios of 123I-metaiodobenzylguanidine uptake (r = 0.6) and between resting HF powers and CVRRs (r = 0.7). The resting LF power was also associated with CVRRs and constipation. Furthermore, a positive correlation was observed between resting LF powers and resting HF powers in patients with PD (r = 0.8).ConclusionsThe power spectral analysis of heart rate variability may be useful as a screening tool for detecting autonomic dysfunctions by detecting low resting LF and HF powers in patients with PD. Sympathetic and parasympathetic nerves may be concurrently damaged in patients with PD.

Influence of antidepressant use on 123I-MIBG heart and lung uptakes in the diagnosis of Lewy body disease

ObjectiveThe clinical significance of decreased physiological lung uptake of 123I-metaiodobenzylguanidine (MIBG) has not been well investigated. This study aimed to elucidate the association between a decrease in lung MIBG uptake with antidepressant intake and the myocardial MIBG uptake in patients who were clinically diagnosed with Lewy body disease (LBD) and patients who were diagnosed as not having LBD.MethodsWe retrospectively reviewed the heart and lung uptakes on 167 consecutive MIBG scans, antidepressant status, and clinical diagnosis of LBD. The images were visually classified into two groups: decreased lung uptake and preserved lung uptake. A semi-quantitative analysis was performed using the heart-to-mediastinum ratio (H/M), lung-to-mediastinum ratio (L/M), and myocardial washout rate (WR).ResultsAll 17 patients with decreased lung uptake were on treated with antidepressants, while none of the 150 patients with preserved lung uptake were treated with any antidepressants. Of the 17 patients with decreased lung uptake, 6 patients were clinically diagnosed as LBD and other 11 were clinically diagnosed as non-LBD. There was not significant difference in early H/M, delayed H/M, and myocardial WR between the 11 non-LBD patients with decreased lung uptake and 83 non-LBD patients with preserved lung uptake (2.87 ± 0.69 vs. 2.89 ± 0.44, 3.09 ± 0.48 vs. 2.98 ± 0.59, and 21.8 ± 11.3% vs. 21.1 ± 12.5%, respectively). Moreover, in LBD patients, there were no significant differences in those values between six patients with decreased lung uptake and 67 patients with preserved lung uptake (1.68 ± 0.32 vs. 1.73 ± 0.42, 1.34 ± 0.21 vs. 1.54 ± 0.57, 46.2 ± 22.8% vs. 42.8 ± 21.3%, respectively).ConclusionsAntidepressants probably blocked MIBG uptake in the lungs, and a decreased lung uptake was not significantly associated with heart uptake. A remarkable decrease in lung uptake can be a signal to check a patient’s medication status.

123I metaiodobenzylguanidine (MIBG) uptake predicts early relapse of neuroblastoma using semi-quantitative SPECT/CT analysis

Objective123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of neuroblastoma (NB). MIBG uptake is correlated with norepinephrine transporter expression; hence, it is expected that high-MIBG tumors would be more highly differentiated and have a better prognosis than those with lower expression. We have introduced a method of assessing MIBG accumulation semi-quantitatively using SPECT/CT fusion images. The purpose of this study was to evaluate the relationship of 123I MIBG uptake measured by semi-quantitative values of SPECT/CT and early relapse of NB.MethodsWe studied the cases of 11 patients (5 males and 6 females, age 5–65 months, median age 20 months) with histopathologically proven NB between April 2010 and March 2015. The early-relapse group was defined as patients who had relapsed within 3 years after the first 123I MIBG SPECT/CT exam. Other patients were classified as the delay-relapse group. Uptake of MIBG was evaluated using the count ratio of tumor and muscles. T/Mmax and T/Mmean were defined as follows: T/Mmax = max count of tumor/max count of muscle, T/Mmean = mean count of tumor/mean count of muscle.ResultsThe average T/Mmean values of the early-relapse group and delay-relapse group were 2.65 ± 0.58 and 7.66 ± 2.68, respectively. The T/Mmean values of the early-relapse group were significantly lower than those of delay-relapse group (p < 0.05). The average T/Mmax of the early-relapse group and delay-relapse group were 8.86 ± 3.22 and 16.20 ± 1.97, respectively. There was no significant difference in T/Mmax values between the two groups.ConclusionsLow 123I MIBG uptake using semi-quantitative SPECT/CT analysis was correlated with early relapse of NB.

Cardiac sympathetic dysfunction associated with dopaminergic depletion in striatal subregions in de novo Parkinson's disease

Objective: It has been documented that low cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) at early stage of illness is associated fast decline in motor and cognitive function in patients with Parkinson's disease (PD). The aim of this study is to investigate the association between cardiac sympathetic dysfunction and striatal subregional dopaminergic depletion in patients with PD.

Sympathetic nervous activity and hemoglobin levels in de novo Parkinson's disease.

Sympathetic nervous denervation may be associated with the development of anemia. We aimed to investigate the association between sympathetic nervous denervation and hemoglobin levels in patients with Parkinson's disease (PD). As indices of sympathetic nervous denervation, we investigated resting norepinephrine levels, increased norepinephrine levels after tilt-up, cardiac uptake of 123I-metaiodobenzylguanidine, supine blood pressure, and the degree of orthostatic hypotension in 132 patients with de novo PD. Older age, female sex, severe motor dysfunction, and lower body mass index were associated with decreased hemoglobin levels. After adjustment for these covariables, resting norepinephrine levels were negatively associated with hemoglobin levels. Hemoglobin levels were not associated with cardiac sympathetic denervation or orthostatic intolerance. Hemoglobin levels in PD seem to be closely related to noradrenergic nervous activity and nigrostriatal dopaminergic degeneration. In contrast to expectations, decreased hemoglobin levels were associated with increased whole-body sympathetic nervous activity in PD.

Clinical profiles of late-onset psychiatric patients exhibiting incidental REM sleep without atonia.

Rapid eye movement (REM) sleep without atonia (RWA), which is a hallmark of REM sleep behavior disorder (RBD) on polysomnography (PSG), may represent specific characteristics of prodromal Parkinson's disease (PD)/dementia with Lewy bodies (DLB), even when dream-enactment behavior is absent. We investigated the clinical profiles associated with PD/DLB in late-onset psychiatric patients exhibiting incidental RWA. Among patients who underwent PSG in our psychiatric ward, eight with incidental RWA, nine with idiopathic RBD, and seven with PD or DLB who had preceding RBD were included. Clinical variables, including the percentage of RWA in the total REM sleep (%RWA), were compared among the three groups. The frequency of depressive disorders as a primary psychiatric diagnosis and antidepressant usage were significantly higher in the incidental RWA group than in the other groups. There were no differences in the prevalence of supportive features of DLB among the three groups. The median %RWA was significantly lower in the incidental RWA group than in the other groups. Although the cardiac 123I-metaiodobenzylguanidine uptake was significantly higher in the incidental RWA group compared with the other groups, the groups showed overlap in the specific binding ratios on dopamine transporter imaging. All patients in the three groups exhibited cingulate island sign ratios on brain perfusion single-photon emission computed tomography within a threshold of 0.281, which is the optimal cut-off value for a diagnosis of DLB. In this series, late-onset psychiatric patients with incidental RWA partially shared common clinical profiles with idiopathic RBD and PD/DLB.

Focal reduction in left ventricular 123I-metaiodobenzylguanidine uptake and impairment in systolic function in patients with Anderson-Fabry disease

BackgroundAbnormalities of cardiac sympathetic innervation have been demonstrated in Anderson-Fabry disease (AFD). We aimed to investigate the relationship between regional left ventricular (LV) denervation and regional function abnormalities. MethodsTwenty-four AFD patients (43.7 ± 12.8 years) were studied by 123I-metaiodobenzylguanidine (MIBG) cardiac imaging and speckle-tracking echocardiography. Segmental tracer uptake was estimated according to 0 to 4 score, and total defect score (TDS) was calculated for each patient. ResultsSegmental longitudinal strain worsened as MIBG uptake score increased (P < 0.001). By ROC analysis, a segmental longitudinal strain > − 16.2% predicted a segmental MIBG uptake score ≥1, with 79.7% sensitivity and 65.3% specificity. Segmental MIBG uptake defects were found in 13 out 24 AFD patients. LV mass index (60.8 ± 10.1 vs. 41.4 ± 9.8 g/h2.7), relative wall thickness (0.51 ± 0.06 vs. 0.40 ± 0.06), systolic pulmonary artery pressure (35.2 ± 6.7 vs. 27.2 ± 4.2 mmHg), and longitudinal strain (− 14.3 ± 2.7 vs. −19.4 ± 1.8%) were significantly higher in patients with segmental defect (all P < 0.01). At multivariate linear regression analysis, global longitudinal strain was independently associated with TDS (B = 3.007, 95% confidence interval 1.384 to 4.630, P = 0.001). ConclusionsReduced cardiac MIBG uptake reflects the severity of cardiac involvement in AFD patients. LV longitudinal function impairment seems to be an earlier disease feature than regional myocardial denervation.

Striatal dopamine activity and myocardial 123I-metaiodobenzylguanidine uptake in early Parkinson's disease

IntroductionDopamine transporter imaging and myocardial 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy have been widely used to diagnose and discriminate degenerative parkinsonism. Many studies have reported that both imaging findings are associated with a variety of motor and non-motor phenomena in Parkinson's disease (PD). However, the association between striatal dopamine activity and myocardial 123I-MIBG uptake has not been well investigated. The objective of this study is to identify the dopamine transporter activity of the corpus striatum and thalamus according to myocardial 123I-MIBG uptake in PD. MethodsNinety-six newly diagnosed, non-medicated PD patients were enrolled. All patients underwent 123I-MIBG myocardial scintigraphy, positron emission tomography (PET) using 18FN-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and T1-weighted magnetic resonance imaging (MRI). Patients were stratified into normal and decreased 123I-MIBG groups according to their delayed heart-to-mediastinum ratio (cutoff value = 1.78). After normalizing the PET images with spatially normalized MRI, the regional standardized uptake value ratios (SUVRs) were analyzed with a volume-of-interest template between the two groups. ResultsThirty-one patients showed normal myocardial 123I-MIBG uptake, and 65 patients showed reduced uptake. The SUVR of the globus pallidus in the group with reduced 123I-MIBG uptake was significantly lower than the SUVR in the normal 123I-MIBG uptake group. The heart-to-mediastinum ratio was correlated well with the SUVR of the globus pallidus, independent of age, disease duration, and the severity of motor symptoms. ConclusionEarly PD patients with normal 123I-MIBG uptake showed a relatively preserved dopamine reserve in the globus pallidus than patients with reduced 123I-MIBG uptake.

Focal Reduction in Cardiac 123I-Metaiodobenzylguanidine Uptake in Patients With Anderson-Fabry Disease.

It remains to be elucidated whether cardiac sympathetic nervous activity is impaired in patients with Anderson-Fabry disease (AFD).Methods and Results:We performed 123I-meta-iodobenzylguanidine (MIBG) scintigraphy and gadolinium-enhanced cardiovascular magnetic resonance (CMR) in 5 AFD patients. MIBG uptake in the inferolateral wall, where wall thinning and delayed enhancement were noted on CMR, was significantly lower compared with the anteroseptal wall. The localized reduction in MIBG uptake was also noted in 2 patients with no obvious abnormal findings on CMR. Cardiac sympathetic nervous activity is impaired in AFD before development of structural myocardial abnormalities. (Circ J 2016; 80: 2550-2551).

Rhinorrhea in Parkinson's disease: A consecutive multicenter study in Japan

Recent reports suggest that rhinorrhea, defined as the presence of a runny nose unrelated to respiratory infections, allergies, or sinus problems, occurs more frequently among patients with Parkinson's disease (PD) than among healthy controls. We conducted a questionnaire survey in a multicenter study throughout Japan and compared the frequency of rhinorrhea between 231 PD and 187 normal control (NC) subjects. After excluding patients with rhinitis or paranasal sinusitis, a total of 159 PD and 59 NC subjects were included in our analysis. Rhinorrhea occurred more frequently in PD patients than NC subjects (33.3% vs. 11.9%; P=0.01). Among PD patients, rhinorrhea was more common in men than women (P=0.005). Rhinorrhea was not correlated with disease duration, modified Hoehn and Yahr score, disease type (akinesia rigidity vs. tremor dominant), or cardiac sympathetic function (evaluated by 123I-metaiodobenzylguanidine uptake). To our knowledge, this is the first multicenter study on the frequency of PD-related rhinorrhea in Asian countries.

Role of cardiac sympathetic nerves in preventing orthostatic hypotension in Parkinson's disease

PurposeCardiac sympathetic denervation is associated with orthostatic hypotension (OH) in Parkinson's disease (PD); however, the physiological role of cardiac sympathetic nerves has yet to be elucidated. To clarify the role of the heart in orthostatic stress, we evaluated whether cardiac sympathetic nerves can alter cardiac activity and systolic blood pressure (BP) in association with elevations or depressions of total peripheral resistance during the head-up tilt test. MethodsNinety-five PD patients and 17 normal controls were enrolled. Using impedance cardiography, we measured total peripheral resistance, stroke volume, heart rate, and systolic BP during the head-up tilt test. Cardiac denervation was defined as a heart-to-mediastinum ratio <1.7 for cardiac 123I-metaiodobenzylguanidine uptake on delayed images. ResultsAt 60° tilt, total peripheral resistance decreased from the initial value in 49 PD patients. Among these, 36 patients exhibited cardiac denervation with severe reductions in systolic BP but little change in stroke volume; among these patients 22 had OH. The remaining 13 patients without cardiac denervation exhibited significant increases in stroke volume and well-preserved systolic BP with no OH. On the other hand, 46 patients had elevations in total peripheral resistance and reduced stroke volume, but little change in systolic BP, regardless of the presence or absence of cardiac denervation. Only one of these patients experienced OH. ConclusionUnder orthostatic stress, cardiac sympathetic denervation with failure to increase total peripheral resistance leads to large reductions in systolic BP. However, patients without cardiac denervation exhibited a positive inotropic response against vasodilatation, which may prevent OH.

Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease

The glucocerebrosidase gene (GBA) is a known risk factor of Parkinson's disease (PD). We sequenced entire coding exons and exon/intron boundaries of GBA in 147 Japanese familial PD (FPD) patients from 144 families and 100 unrelated control subjects. Twenty-seven of 144 (18.8%) of index patients were heterozygous for known Gaucher disease mutations, suggesting that GBA heterozygous mutations are strongly associated with FPD (odds ratio = 22.9, 95% confidence interval = 3.1–171.2). The frequency was significantly higher in autosomal dominant PD (ADPD) compared with autosomal recessive PD. According to clinical assessments, PD patients with GBA mutations exhibited typical manifestations of PD or dementia with Lewy bodies (DLB), such as L-dopa responsive parkinsonism with psychiatric problems and/or cognitive decline. Interestingly, they also presented with reduced myocardial 123I-metaiodobenzylguanidine uptake. Our findings suggest that heterozygous GBA mutations are strong risk factors in FPD, especially for autosomal dominant PD. Some patients with GBA heterozygous mutations develop clinical features of DLB. We speculate that GBA dysfunction may promote Lewy body formation, resulting in more severe PD or DLB phenotypes that are inherited in families.

Reduced cardiac 123I-metaiodobenzylguanidine uptake in patients with spinocerebellar ataxia type 2: a comparative study with Parkinson’s disease

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder characterized by cerebellar ataxia, supranuclear ophthalmoplegia, and peripheral neuropathy. Autonomic nervous system dysfunction is often present. This study evaluated the cardiac sympathetic function in patients with SCA2 using (123)I-metaiodobenzylguanidine (MIBG) in comparison with patients with Parkinson's disease (PD) and control subjects. Nine patients with SCA2, nine patients with PD, and nine control subjects underwent (123)I-MIBG imaging studies from which early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates were calculated. Early (F = 12.3, p < 0.0001) and late (F = 16.8, p < 0.0001) H/M ratios were significantly different among groups. In controls, early and late H/M ratios (2.2 ± 0.12 and 2.1 ± 0.20) were significantly higher than in patients with SCA2 (1.9 ± 0.23 and 1.8 ± 0.20, both p < 0.05) and with patients with PD (1.7 ± 0.29 and 1.4 ± 0.35, both p < 0.001). There was also a significant difference in washout rates among groups (F = 11.7, p < 0.0001). In controls the washout rate (19.9 ± 9.6%) was significantly lower (p < 0.005) than in patients with PD (51.0 ± 23.7%), but not different from that in SCA2 patients (19.5 ± 9.4%). In SCA2 patients, in a multivariable linear regression analysis only the Scale for the Assessment and Rating of Ataxia score was independently associated with early H/M ratio (β = -0.12, p < 0.05). (123)I-MIBG myocardial scintigraphy demonstrated an impairment of cardiac sympathetic function in patients with SCA2, which was less marked than in PD patients. These results suggest that (123)I-MIBG cardiac imaging could become a useful tool for analysing the pathophysiology of SCA2.

Catecholamines influence myocardial 123I MIBG uptake in neuroblastoma patients

Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. 30 neuroblastoma patients were retrospectively assessed on cardiac 123I MIBG uptake and urinary catecholamine dopamine and metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA). Cardiac 123I MIBG uptake was quantified by heart-to-mediastinum (H/M) ratios, which were calculated into standard deviation scores (SDS) using age-specific reference values. In 17 (57%) and 12 patients (40%) H/M ratio measurements were below -1.0 and -2.0 SDS at diagnosis. A significant inverse correlation between the average of urine metabolites HVA and VMA, and H/M ratio SDS was observed (r -.39, p = 0.04). Furthermore, there was a significant correlation between the urinary catecholamine metabolite HVA and H/M ratio SDS (r -.40, p=0.04). Routine calculation of H/M ratios in 123I MIBG scintigrams of neuroblastoma patients is not helpful because it will not identify cardiac ventricular dysfunction in this patient category. A low H/M ratio on 123I MIBG scintigraphy is explained by increased cathecholamine levels secreted by neuroblastoma tumours.

Combination of transcranial sonography, olfactory testing, and MIBG myocardial scintigraphy as a diagnostic indicator for Parkinson’s disease

Appropriate diagnostic biomarkers are useful for improving speed and accuracy of a diagnosis. Substantia nigra (SN) hyperechogenicity visualized by transcranial sonography (TCS), olfactory dysfunction, and the reduced uptake of (123) I-metaiodobenzylguanidine (MIBG) in myocardial scintigraphy have been suggested as potential biomarkers for the identification of Parkinson's disease (PD). To evaluate the diagnostic potential of these tests and to determine whether combining them increases their diagnostic power. Subjects were 44 patients with clinically diagnosed PD and 36 healthy controls. TCS of the SN, the odor stick identification test for Japanese (OSIT-J), and MIBG myocardial scintigraphy were conducted. Eleven patients with PD (25%) and four controls (11%) were excluded because of an insufficient acoustic temporal bone window in the TCS. Thus, 33 patients with PD and 32 healthy controls were finally included. The diagnostic sensitivity of TCS, OSIT-J, and MIBG myocardial scintigraphy was 78.8%, 84.8%, and 60.6%, respectively. The specificity of TCS and OSIT-J was 93.8% and 78.1%, respectively. The combination of TCS of the SN and OSIT-J substantially increased the sensitivity to a sufficient level for discriminating patients with PD from controls. TCS of the SN and olfactory testing play complementary roles in increasing diagnostic power in PD. As both tests are easy to perform, noninvasive, and inexpensive, the combination of TCS of the SN and olfactory testing may contribute to early and accurate diagnosis of PD.

Effects of peripheral lymphocyte subpopulations and the clinical correlation with Parkinson's disease

To understand the characteristics of peripheral immunity in patients with Parkinson's disease (PD), we investigated the natural killer (NK) cell activity and lymphocyte subpopulations including regulatory T (Treg) cells and type 17 helper T (Th17) cells. Peripheral blood was collected from 29 PD patients (mean age 70.4 years) and 30 healthy controls (mean age 68.9 years). NK cell activity was measured by a calcein acetoxymethyl ester release assay using NK-sensitive K562 cells, peripheral NK cells and lymphocytes subsets were analyzed using flow cytometry techniques. Comparison of the two groups demonstrated that the percentage of NK cells increased and that of helper T cells, particularly type 1 (Th1), decreased in patients with PD. There was no evidence of Th1/Th2 or Treg/Th17 cell predominance in PD. Moreover, the increase of NK cells and the decrease of Th1 cells correlated with Unified Parkinson's Disease Rating Scale scores and the heart-to-mediastinum ratios based on myocardial (123) I-metaiodobenzylguanidine uptake, both of which represent disease severity in patients with PD. Our investigation indicates that a certain proportion of NK cells and other lymphocytes in the peripheral blood of patients with PD and their association with disease severity may reflect the effect of innate immunity in patients with PD in addition to the effect of dopaminergic-related agents.

Olfactory deficits and cardiac 123I‐MIBG in Parkinson's disease related to the LRRK2 R1441G and G2019S mutations

It has been proposed that olfactory tests and metaiodobenzylguanidine cardiac scintigraphy may help diagnose idiopathic Parkinson's disease in the premotor phase. However, it is not clear what value these tests have in all patients with Parkinson's disease and, particularly, in those who carry mutations in LRRK2. The objective was to analyze olfactory dysfunction and the changes in cardiac I-metaiodobenzylguanidine uptake in patients with Parkinson's disease carrying the R1441G and G2019S mutations in LRRK2, and in patients with Parkinson's disease with no known mutations. Patients with Parkinson's disease were screened for R1441G and G2019S LRRK2 gene mutations and classified as LRRK2 mutation carriers or noncarriers. A total of 190 patients with Parkinson's disease (44 LRRK2 mutation carriers) were tested for olfactory dysfunction using the Brief Smell Identification Test. Cardiac (123) I-metaiodobenzylguanidine scintigraphy was performed on 90 patients with Parkinson's disease (27 LRRK2 mutation carriers). Thirty-six percent of patients with LRRK2 mutations have hyposmia, compared to 75% of noncarrier patients with Parkinson's disease (P < .001). Sixty-six percent of LRRK2 mutation carriers have low early metaiodobenzylguanidine uptake, compared to 86% of noncarriers (P = .048). Similarly, the heart/mediastinum ratio in delayed metaiodobenzylguanidine images appeared to differ between these groups of patients with Parkinson's disease, although these results did not reach statistical significance. The data obtained indicate that olfactory and cardiac impairment is less prevalent when Parkinson's disease is associated with mutations in LRRK2, although the underlying mechanisms for this difference remain unclear. Thus, such screening would be less useful to detect the premotor phase in asymptomatic relatives who carry mutations in LRRK2 than in cases not associated with LRRK2.

Does cardiovascular autonomic dysfunction contribute to fatigue in Parkinson's disease?

Patients with Parkinson's disease often complain of fatigue, and although cardiac sympathetic denervation is thought to be associated with fatigue, this link remains unclear. Previously, we detected cardiac sympathetic denervation in patients with Parkinson's disease using dobutamine, a selective beta-1 stimulant. To clarify the involvement of autonomic dysfunction in fatigue in Parkinson's disease, we conducted autonomic function tests on 33 patients with Parkinson's disease (mean age, 66.1 ± 5.6 years; 20 men, 13 women) and evaluated their relationships to fatigue. We divided patients into 2 groups, fatigued (n = 12) and nonfatigued (n = 21), based on an average score ≥ 3.3 on the Parkinson fatigue scale. Autonomic function tests included the coefficient of variation of R-R intervals, head-up tilt test, norepinephrine and dobutamine infusion tests, and cardiac (123) I-metaiodobenzylguanidine scintigraphy. The coefficient of variation of R-R intervals and the systolic blood pressure changes accompanying the head-up tilt test did not show significant differences between the 2 groups; however, the pressor responses in the norepinephrine and dobutamine infusion tests were significantly greater in the fatigued group than in the nonfatigued group. The (123) I-metaiodobenzylguanidine heart-to-mediastinal uptake ratio was lower in the fatigued group than in the nonfatigued group. Partial correlation analyses, using disease duration and Hoehn and Yahr stage as control variables, also demonstrated significant correlations between the Parkinson fatigue scale score and the results of the autonomic function tests and cardiac (123) I-metaiodobenzylguanidine uptake. Our results suggest that autonomic dysfunction, including cardiac sympathetic denervation, is associated with fatigue in patients with Parkinson's disease.

Meta‐analysis of 123I‐MIBG cardiac scintigraphy for the diagnosis of Lewy body–related disorders

Patients with parkinsonism pose a diagnostic challenge. Parkinson's disease may be difficult to distinguish from multiple system atrophy and progressive supranuclear palsy, whereas Parkinson's disease and dementia with Lewy bodies can be difficult to distinguish from Alzheimer's disease and other dementias. A number of studies have found diminished cardiac (123) I-metaiodobenzylguanidine uptake in Lewy body-related conditions (Parkinson's disease and Lewy body dementia). In 2005, the Dementia With Lewy Bodies Consortium considered (123) I-metaiodobenzylguanidine cardiac scintigraphy a "supportive" diagnostic feature, based on limited evidence. We report a meta-analysis of the literature and an assessment of the utility of (123) I-metaiodobenzylguanidine for the diagnosis of dementia with Lewy bodies and Parkinson's disease. A search was conducted of articles published between 1950 and June 2010. Forty-six studies involving neuropsychiatric and movement disorders, comprising 2680 subjects, were included in the analysis. A mixed-effects regression model was used to analyze the delayed mean heart-to-mediastinum ratio of (123) I-metaiodobenzylguanidine uptake. (123) I-metaiodobenzylguanidine cardiac scintigraphy sensitively detected and specifically distinguished 2 diagnostic clusters: (1) Parkinson's disease, dementia with Lewy bodies, and rapid eye movement sleep behavior disorder; and (2) normal controls and patients with Alzheimer's disease, multiple system atrophy, progressive supranuclear palsy, vascular dementia, and frontotemporal dementia. The area under the receiver operating characteristic curve was 0.987 at a cluster discriminatory heart-to-mediastinum ratio threshold of 1.77. This threshold yielded 94% sensitivity and 91% specificity for the discrimination of these diagnostic clusters. (123) I-metaiodobenzylguanidine cardiac scintigraphy can accurately distinguish between 2 movement disorders, Parkinson's disease and multiple system atrophy, and between 2 common causes of dementia, Alzheimer's disease and dementia with Lewy bodies. © 2011 Movement Disorder Society.