Cardiovascular dysautonomia and cognitive impairment in Parkinson's disease (Review).

Cognitive impairment is a prevalent non-motor symptom of Parkinson's disease (PD), which can result in significant disability and distress for patients and caregivers. There is a marked variation in the timing, characteristics and rate at which cognitive decline occurs in patients with PD. This decline can vary from normal cognition to mild cognitive impairment and dementia. Cognitive impairment is associated with several pathophysiological mechanisms, including the accumulation of ß-amyloid and tau in the brain, oxidative stress and neuroinflammation. Cardiovascular autonomic dysfunctions are commonly observed in patients with PD. These dysfunctions play a role in the progression of cognitive impairment, the incidents of falls and even in mortality. The majority of symptoms of dysautonomia arise from changes in the peripheral autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. Cardiovascular changes, including orthostatic hypotension, supine hypertension and abnormal nocturnal blood pressure (BP), can occur in both the early and advanced stages of PD. These changes tend to increase as the disease advances. The present review aimed to describe the cognitive changes in the setting of cardiovascular dysautonomia and to discuss strategies through which these changes can be modified and managed. It is a multifactorial process usually involving decreased blood flow to the brain, resulting in the development of cerebral ischemic lesions, an increased presence of abnormal white matter signals in the brain, and a potential influence on the process of neurodegeneration in PD. Another possible explanation is this association being independent observations of PD progression. Patients with clinical symptoms of dysautonomia should undergo 24-h ambulatory BP monitoring, as they are frequently subtle and underdiagnosed.

Radioligand therapy in sympathetic-adrenal-medullary axis tumors: state of art and perspectives.

The approval in 2017 by the European Medicines Agency (EMA) and in 2018 by the US Food and Drug Administration (FDA) of radioligand therapy (RLT) led to its wide application in therapeutic management of neuroendocrine neoplasms (NENs). However, the indications are currently limited to certain specific histotypes belonging to the broader NEN's family, mainly advanced well-differentiated gastro-entero-pancreatic NENs. As a consequence, several other tumors of the NEN spectrum that can potentially benefit, due to their biological characteristics, from RLT are still ineligible and can be considered "RLT-orphans". Among those, the subgroup of NENs originating from the sympathetic-adrenal-medullary (SAM) axis can be listed. This paper discusses the state of art and perspectives of the theragnostic applications in pheochromocytomas and paragangliomas, considering both the traditional theragnostic model - with radiolabelled metaiodobenzylguanidine (MIBG) - and the innovative one with radiolabeled somatostatin analogs (SSAs), that will hopefully become available for these patients in the near future.

Relationships between neuroimaging biomarkers and glymphatic-system activity in dementia with Lewy bodies.

Alpha-synuclein deposits in the brain have been suspected to cause Parkinson's disease and dementia with Lewy bodies (DLB). It was recently revealed that the glymphatic system is largely responsible for the removal of alpha-synuclein. We investigated changes in the glymphatic system's activity by determining the DTI­ALPS (diffusion tensor image analysis along the perivascular space) index in DLB patients. Twenty-six patients with DLB and 43 healthy subjects underwent diffusion tensor imaging (DTI) scanning at our hospital during the period April 2013 to March 2023. We retrospectively computed each subject's DTI­ALPS index to evaluate his/her glymphatic-system activity and then analyzed the relationships between the subjects' DTI­ALPS index data and their DLB neuroimaging biomarker values. A significant reduction of the DTI­ALPS index was observed in the patients with DLB compared to the healthy subjects. Significant positive correlations were also detected in the DLB group between the DTI­ALPS index and the regional gray matter volume in the left insula and between the index and the specific binding ratio of 123I-N-ω-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)nortropane ([123I]-FP-CIT). These results indicate that (i) the DTI­ALPS index is a good biomarker of the progression of DLB, and (ii) this index might be effective to distinguish DLB from other neurocognitive disorders.

Associations of cerebrospinal fluid monoamine metabolites with striatal dopamine transporter binding and 123I-meta-iodobenzylguanidine cardiac scintigraphy in Parkinson's disease: Multivariate analyses.

Cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA), dopamine and serotonin metabolites, are decreased in Parkinson's disease (PD). Although some reported associations between HVA and striatal dopamine transporter (DAT) or 5-HIAA and cardiac 123I-meta-iodobenzylguanidine (MIBG) findings, respectively, whether these are direct associations remained unknown. We retrospectively reviewed 57 drug-naïve patients with PD who underwent CSF analyses and DAT and cardiac MIBG imaging. Z-score of striatal DAT specific binding ratio (Z-SBR) was measured, and the positivity of MIBG abnormalities were judged by an expert. The mean age was 75.5 ± 8.7 years. Thirty-three were MIBG-positive and 24 were MIBG-negative. 5-HIAA levels were significantly lower in the MIBG-positive group. Logistic regression analysis showed that MIBG positivity was associated with 5-HIAA level (odds ratio = 0.751, p = 0.006) but not with age, sex, and HVA. DAT Z-SBR correlated with both HVA and 5-HIAA. Multiple regression analysis showed that HVA was the only significant variable associated with Z-SBR (t = 3.510, p < 0.001). We confirmed direct associations between 5-HIAA and cardiac MIBG, and between HVA and striatal DAT binding.

Adrenal ganglioneuroma with nodal metastases on 123I-MIBG SPECT/CT and 18F-FDG PET/CT.

Ganglioneuroma is a well-differentiated tumor originating from neural crest cells of the sympathetic nervous system. Although benign, a few cases have been reported that ganglioneuroma can metastasize to other sites. We report a case of adrenal ganglioneuroma with para-aortic nodal metastases with low FDG and MIBG uptake. In order to avoid unnecessary wide excision or aggressive medication, it is important to consider the possibility of ganglioneuroma preoperatively even if with metastases.

Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease.

BACKGROUND: This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes. METHODS: In this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls. RESULTS: Significant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently. CONCLUSIONS: Our findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies.

Urodynamic study and its correlation with cardiac meta-iodobenzylguanidine (MIBG) in body-first and brain-first subtypes of Parkinson's disease.

BACKGROUND AND PURPOSE: Lower urinary tract symptoms (LUTS) are frequently observed in patients with Parkinson's disease (PD), but the underlying mechanism remains elusive. The concept of "body-first" and "brain-first" subtypes in PD has been proposed, but the correlation of PD subtype with LUTS remains unclear. We aimed to investigate the disparities in urological dysfunctions between body-first and brain-first subtypes of PD using urodynamic studies (UDS). METHODS: We reviewed patients with PD (disease duration <3 years) who had undergone UDS and completed urological questionnaires (Overactive Bladder Symptom Score [OABSS] and International Prostate Symptom Score [IPSS]) and a voiding diary. Patients were categorized as having body-first or brain-first PD based on cardiac sympathetic denervation (CSD) using cardiac meta-iodobenzylguanidine (MIBG) uptake and the presence of rapid eye movement sleep behavior disorder (RBD), assessed using a questionnaire (PD with CSD and RBD indicating the body-first subtype). RESULTS: A total of 55 patients with PD were categorized into body-first PD (n = 37) and brain-first PD (n = 18) groups. The body-first PD group exhibited smaller voiding volume and first desire volume (FDV) than the brain-first PD group (p < 0.05 in both). Also, the body-first PD group had higher OABSS and IPSS scores, and higher prevalence of overactive bladder diagnosed by OABSS, compared to the brain-first PD group. In multiple linear regression, cardiac MIBG uptake was positively correlated with FDV and voiding volume and negatively correlated with OABSS and IPSS (p < 0.05 in all). CONCLUSIONS: Patients with the body-first PD subtype exhibited more pronounced overactive bladder symptoms and impaired storage function in the early stage of disease. Additionally, cardiac MIBG was significantly associated with urological dysfunction.

Serum phosphorus levels associated with nigrostriatal dopaminergic deficits in drug-naïve Parkinson's disease.

INTRODUCTION: A major component of Lewy bodies is phosphorylated α-synuclein. This post-translational modification of α-synuclein, phosphorylation, may consume a great amount of serum phosphorus. We aimed to investigate serum phosphorus levels and their associations with clinical phenotype and the degeneration of cardiac sympathetic and nigrostriatal dopaminergic neurons in patients with Parkinson's disease (PD). MATERIALS AND METHODS: We examined serum phosphorus levels in 127 participants (drug-naïve PD, 97; age- and sex-matched controls, 30). Associations of serum phosphorus levels with clinical features, heart-to-mediastinum (H/M) ratio on cardiac 123I-metaiodobenzylguanidine scintigraphy and striatal specific binding ratio of 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) were examined. RESULTS: Serum phosphorus levels were 3.4 ± 0.5 mg/dL in patients with PD and were not different from those in controls after controlling for age and sex (p = 0.850). Serum phosphorus levels were significantly lower in patients with PD and decreased H/M ratio than in those with PD and normal H/M ratio (3.3 ± 0.4 mg/dL vs. 3.6 ± 0.5 mg/dL, p = 0.003). Lower serum phosphorus levels were significantly associated with more severe degeneration of nigrostriatal dopaminergic neurons in patients with PD and decreased H/M ratio. However, this association was not observed in patients with PD and normal H/M ratio. CONCLUSIONS: Serum phosphorus levels and their association with nigrostriatal dopaminergic degeneration are different between patients with decreased H/M ratio and those with normal H/M ratio. Serum phosphorus levels may reflect the degree of nigrostriatal dopaminergic degeneration in patients with decreased H/M ratio, namely, Body-First PD.

Dopa-responsive Rest Tremor Preceding Tachyphemia in Progressive Supranuclear Palsy: A Case Report.

Progressive supranuclear palsy (PSP) is characterized by progressive postural instability, falls, and supranuclear vertical gaze abnormalities. In this report, we present the case of a 71-year-old woman with dopa-responsive rest tremor followed by tachyphemia and postural instability. She initially presented with dopa-responsive slowness and tremor in the right hand. Two years later, she developed speech difficulties (tachyphemia) and a propensity for falls. Based on the diagnostic criteria for PSP, the patient was diagnosed with probable PSP-RS. The clinical manifestations observed in our patient are unique and are considered important for illustrating a broad spectrum of PSP syndrome.

Quantitative assessment of cardiac 123iodo-metaiodobenzylguanidine SPECT/CT in patients with arrhythmogenic right ventricular cardiomyopathy: Novel insight in disease monitoring.

BACKGROUND: The heart-to-mediastinum ratio (H/M-Ratio) of 123iodo-metaiodobenzylguanidine (123I-MIBG) represents state-of-the-art assessment for sympathetic dysfunction in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to evaluate quantitative reconstruction of 123I-MIBG uptake and to demonstrate its correlation with echocardiographic parameters. METHODS: Cardiac innervation was assessed in 23 patients diagnosed with definite ARVC or borderline ARVC and 12 patients with other cardiac disease presenting arrhythmia, using quantitative 123I-MIBG Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) imaging. Tracer uptake was evaluated in the left (LV) and right ventricle (RV) based on a CT scan after quantitative image reconstruction. The relationship between tracer uptake and echocardiographic parameter data was examined. RESULTS: Absolute quantification of 123I-MIBG uptake in the LV and RV is feasible and correlates accurately with the gold standard H/M Ratio. When comparing sensitivity and specificity, the area under the curve (AUC) favors standardized uptake value (SUV) of the RV over the right-ventricle-to-mediastinum-ratio (RV/M-Ratio) for diagnosing ARVC. A reduced RV-SUV in patients with definite ARVC is associated with reduced RV function. RV polar maps revealed globally reduced 123I-MIBG uptake without segment-specific reduction in the RV. CONCLUSIONS: Quantitative 123I-MIBG SPECT in ARCV patients offers robust potential for clinical reporting and demonstrates a significant correlation with RV function. Segmental RV analysis needs to be evaluated in larger samples. In summary, cardiac 123I-MIBG imaging using SUV could facilitate image-guided therapy in patients diagnosed with ARVC.

Response-adapted consolidation therapy strategy for patients with metastatic high-risk neuroblastoma: Results of the SMC NB-2014 study.

BACKGROUND: Tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) and incorporation of 131I-metaiodobenzylguanidine (131I-MIBG) treatment have shown positive outcomes in high-risk neuroblastoma. However, more optimized treatment strategies are still needed. PROCEDURE: The NB-2014 study was a nonrandomized, prospective trial that examined survival outcomes in metastatic high-risk neuroblastoma patients using response-adapted consolidation therapy. We used post-induction residual 123I-MIBG status at metastatic sites as a treatment response marker. Patients achieving complete resolution of MIBG uptake at metastatic sites underwent a reduced first HDCT/auto-SCT with a 20% dose reduction in HDCT. After the first HDCT/auto-SCT, patients with remaining MIBG uptake received dose-escalated (18 mCi/kg) 131I-MIBG treatment. In contrast, those with complete resolution of MIBG at metastatic sites received a standard dose (12 mCi/kg) of 131I-MIBG. We compared survival and toxicity outcomes with a historical control group from the NB-2009. RESULTS: Of 65 patients treated, 63% achieved complete resolution of MIBG uptake at metastatic sites following induction chemotherapy, while 29% of patients still had MIBG uptake at metastatic sites after the first HDCT/auto-SCT. The 3-year event-free survival (EFS) and overall survival (OS) rates were 68.2% ± 6.0% and 86.5% ± 4.5%, respectively. Compared to NB-2009, EFS was similar (p = .855); however, NB-2014 had a higher OS (p = .031), a lower cumulative incidence of treatment-related mortality (p = .036), and fewer acute and late toxicities. CONCLUSIONS: Our results suggest that response-adaptive consolidation therapy based on chemotherapy response at metastatic sites facilitates better treatment tailoring, and appears promising for patients with metastatic high-risk neuroblastoma.

Predictors of appropriate therapies delivered by the implantable cardioverter-defibrillator in patients with coronary artery disease during long-term period.

This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.

Accuracy of patient-specific I-131 dosimetry using hybrid whole-body planar-SPECT/CT I-123 and I-131 imaging.

PURPOSE: This study aimed to assess the accuracy of patient-specific absorbed dose calculations for tumours and organs at risk in radiopharmaceutical therapy planning, utilizing hybrid planar-SPECT/CT imaging. METHODS: Three Monte Carlo (MC) simulated digital patient phantoms were created, with time-activity data for mIBG labelled to I-123 (LEHR and ME collimators) and I-131 (HE collimator). The study assessed the accuracy of the mean absorbed doses for I-131-mIBG therapy treatment planning. Multiple planar whole-body (WB) images were simulated (between 1 to 72 h post-injection (p.i)). The geometric-mean image of the anterior and posterior WB images was calculated, with scatter and attenuation corrections applied. Time-activity curves were created for regions of interest over the liver and two tumours (diameters: 3.0 cm and 5.0 cm) in the WB images. A corresponding SPECT study was simulated at 24 h p.i and reconstructed using the OS-EM algorithm, incorporating scatter, attenuation, collimator-detector response, septal scatter and penetration corrections. MC voxel-based absorbed dose rate calculations used two image sets, (i) the activity distribution represented by the SPECT images and (ii) the activity distribution from the SPECT images distributed uniformly within the volume of interest. Mean absorbed doses were calculated considering photon and charged particle emissions, and beta emissions only. True absorbed doses were calculated by MC voxel-based dosimetry of the known activity distributions for reference. RESULTS: Considering photon and charged particle emissions, mean absorbed dose accuracies across all three radionuclide-collimator combinations of 3.8 ± 5.5% and 0.1 ± 0.9% (liver), 5.2 ± 10.0% and 4.3 ± 1.7% (3.0 cm tumour) and 15.0 ± 5.8% and 2.6 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. Considering charged particle emissions, accuracies of 2.7 ± 4.1% and 5.7 ± 0.7% (liver), 3.2 ± 10.2% and 9.1 ± 1.7% (3.0 cm tumour) and 13.6 ± 5.7% and 7.0 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. CONCLUSION: The hybrid WB planar-SPECT/CT method proved accurate for I-131-mIBG dosimetry, suggesting its potential for personalized treatment planning.

Navigating new horizons: Prospects of NET-targeted radiopharmaceuticals in precision medicine.

In the evolving landscape of precision medicine, NET-targeted radiopharmaceuticals are emerging as pivotal tools for the diagnosis and treatment of a range of conditions, from heart failure and neurodegenerative disorders to neuroendocrine cancers. This review evaluates the advancements offered by 18F-labeled PET tracers and 211At alpha-particle therapy, juxtaposed with current 123I-MIBG SPECT and 131I-MIBG therapies. The enhanced spatial resolution and capability for quantitative analysis render 18F-labeled PET tracers potential candidates for improved detection and management of diseases. Alpha-particle therapy with 211At may offer increased specificity and tumoricidal efficacy, pointing towards a shift in therapeutic protocols. While preliminary data is promising, these innovative approaches require thorough validation against current modalities. Ongoing clinical trials are pivotal to confirm the expected clinical benefits and to address safety concerns. This review underscores the need for rigorous research to verify the clinical utility of NET-targeted radiopharmaceuticals, which may redefine precision medicine paradigms and significantly impact patient care.

Aurora Kinase A inhibition enhances DNA damage and tumor cell death with 131I-MIBG therapy in high-risk neuroblastoma.

BACKGROUND: Neuroblastoma is the most common extra-cranial pediatric solid tumor. 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 131I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma. RESULTS: Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of 131I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels. CONCLUSION: The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.

Radio theranostics in paragangliomas and pheochromocytomas.

This continuing education aims to present in a clear and easy-to-understand manner the biology of paragangliomas and pheochromocytomas (PPGLs), the functional imaging studies available for their diagnosis and therapeutic planning, the requirements necessary to administer radioligand therapy (RLT) and the characteristics of these treatments (inclusion criteria, administration protocols, adverse effects and future perspectives). In this pathology we have two RLT options: [131I]MIBG and [177Lu]Lu-DOTA-TATE. The indication for treatment is determined by the expression of its therapeutic target in functional imaging studies, allowing precision and personalized medicine. Although most of the results we have for both treatments have as origin small retrospective series, RLT is presented as a safe and well-tolerated therapeutic option in PPGLs with slow-moderate progression or with uncontrollable symptoms, obtaining high disease control rates.

Reduced cardiac 123I-MIBG uptake is a robust biomarker of Lewy body disease in isolated rapid eye movement sleep behaviour disorder.

Cardiac 123I-MIBG scintigraphy is used to assess the function of postganglionic presynaptic cardiac sympathetic nerve endings. 123I-MIBG cardiac uptake is markedly reduced in patients with isolated rapid eye movement sleep behaviour disorder, similar to Parkinson's disease and dementia with Lewy bodies. As a result, it can be used as an early biomarker of isolated rapid eye movement sleep behaviour disorder. Most patients with isolated rapid eye movement sleep behaviour disorder develop synucleinopathies: Parkinson's disease, dementia with Lewy bodies or multiple system atrophy. We aimed to investigate whether cardiac postganglionic denervation is present in patients with isolated rapid eye movement sleep behaviour disorder, as well as its possible usefulness as a marker for Lewy body disease status. This retrospective cohort study examined 306 patients (236 men and 70 women; mean age: 68.2 years; age range: 43-87 years) with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder who were followed for 1-3 months and underwent 123I-MIBG scintigraphy. We retrospectively analysed data from 306 patients with polysomnography-confirmed isolated rapid eye movement sleep behaviour disorder, and their longitudinal outcomes were documented at two centres. Among isolated rapid eye movement sleep behaviour disorder patients, reduced 123I-MIBG uptake was observed in the early and delayed images in 84.4 and 93.4% of patients, respectively, whereas 88.6% of the patients had a high washout rate. This large Japanese two-cohort study (n = 306) found that 91 patients (29.7%) developed an overt synucleinopathy (51 Parkinson's disease, 35 dementia with Lewy bodies, 4 multiple system atrophy, and 1 cerebellar ataxia) during a mean follow-up duration of 4.72 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.4% at 5 years, 41.4% at 8 years and 52.5% at 10 years. On the other hand, among patients with heart-to-mediastinum ratio < 2.2 in the delayed images (n = 286), 85 (29.7%) developed Parkinson's disease or dementia with Lewy bodies during a mean follow-up duration of 4.71 ± 3.94 years, with a conversion risk of 14.5% at 3 years, 25.6% at 5 years, 42.0% at 8 years and 51.0% at 10 years. Among the 33 patients who underwent repeat 123I-MIBG scintigraphy, there was a progressive decline in uptake over the next 4.2 years, with patients exhibiting reduced uptake progressing to Parkinson's disease or dementia with Lewy bodies. In contrast, patients without decreased 123I-MIBG uptake progressed to multiple system atrophy. Reduced cardiac 123I-MIBG uptake was detected in over 90% of isolated rapid eye movement sleep behaviour disorder patients, with progression to Parkinson's disease or dementia with Lewy bodies, rather than multiple system atrophy, over time. Reduced 123I-MIBG uptake is a robust maker for Lewy body disease among isolated rapid eye movement sleep behaviour disorder patients.

Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

Chagas Cardiomyopathy and Myocardial Sympathetic Denervation.

PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.