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Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and neuropsychiatric symptoms resulting from the loss of dopamine-producing neurons in the substantia nigra pars compacta (SNc). Dopamine transporter scan (DATSCAN), based on single-photon emission computed tomography (SPECT), is commonly used to evaluate the loss of dopaminergic neurons in the striatum. This study aims to identify a biomarker from DATSCAN images and develop a machine learning (ML) algorithm for PD diagnosis. Using 13 DATSCAN-derived parameters and patient handedness from 1309 individuals in the Parkinson's Progression Markers Initiative (PPMI) database, we trained an AdaBoost classifier, achieving an accuracy of 98.88% and an area under the receiver operating characteristic (ROC) curve of 99.81%. To ensure interpretability, we applied the local interpretable model-agnostic explainer (LIME), identifying contralateral putamen SBR as the most predictive feature for distinguishing PD from healthy controls. By focusing on a single biomarker, our approach simplifies PD diagnosis, integrates seamlessly into clinical workflows, and provides interpretable, actionable insights. Although DATSCAN has limitations in detecting early-stage PD, our study demonstrates the potential of ML to enhance diagnostic precision, contributing to improved clinical decision-making and patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The α-Synuclein Origin and Connectome (SOC) model recently proposed two different Parkinson’s Disease (PD) phenotypes clinically based on the relationship between REM sleep behavior disorder (RBD) and motor symptoms’ onset: a “body first” phenotype and a “brain first” phenotype in which RBD precedes or may follow the motor onset, respectively. A higher burden of non-motor symptoms as well as a more symmetrical clinical presentation have also been predicted in the body-first phenotype. This point has been poorly assessed through semi-quantitative striatal dopaminergic functional imaging to date. Objectives: To explore the relation between RBD onset and striatal dysfunction in PD. Methods: PD patients were retrospectively enrolled and clinical follow-up data were gathered. Presence and onset of probable RBD were evaluated classifying patients into PD-RBDpre (onset before motor symptoms), PD-RBDpost (onset after motor symptoms) and PD-RBD-. Semi-quantitative 123I-FP-CIT-DAT-SPECT imaging was performed at baseline. Mean putamen and caudate-specific binding ratios (SBR) and asymmetry index (AI) were computed. Results: Fifty-six PD patients were enrolled (10 PD-RBDpre, 19 PD-RBDpost and 27 PD-RBD-). A more symmetrical motor impairment, higher mild cognitive impairment (MCI) prevalence, lower caudate SBR and lower putamen AI were found in PD-RBDpre. A negative trend in MCI prevalence as well as a positive trend in both caudate SBR and putamen AI were found across PD-RBDpre, PD-RBDpost and PD-RBD-. Conclusions: Different patterns of striatal dopaminergic dysfunction and cognitive impairment based on RBD onset were unraveled, supporting the SOC model’s predictions. [ABSTRACT FROM AUTHOR]

Introduction: Drug-induced parkinsonism (DIP) is one of the most common iatrogenic movement disorders. It is characterized by tremors, slowness of movement, and shuffling gait with postural instability, clinically indistinguishable from idiopathic Parkinson's disease. Prior exposure to antipsychotic medications or other dopamine receptor blocking agents (DRBAs) is required for the diagnosis. Areas covered: This article aims to review the epidemiology, pathophysiology, clinical features, ancillary testing, and treatment of DIP. A literature search was undertaken in PubMed from January 2013 to January 2024. Expert opinion: A clinician's suspicion of DIP must always be present when a patient develops acute to subacute onset of parkinsonism while taking a DRBA. As DIP can be indistinguishable from idiopathic PD, ancillary testing, such as DaTscans and skin biopsy searching for alpha-synuclein deposits, are often required to make a definitive diagnosis. When DIP develops, steps should be taken to discontinue the offending agent or, in the case of antipsychotics, dose reduction or change to an agent with lower risk for DIP, such as quetiapine or clozapine. Prophylactic treatment with anticholinergics is not indicated. [ABSTRACT FROM AUTHOR]

Background: Quantitative thresholds are helpful to define an abnormal DaT SPECT in patients with suspected nigrostriatal degenerative diseases (NSDD). The optimal DaTQUANT threshold for diagnostic accuracy of DaT SPECT across combined movement and cognitive disorder populations has been previously described. Methods: We established optimal DaTQUANT thresholds that enhance the discrimination between dementia with Lewy bodies (DLB) and non-DLB dementia types, as well as between Parkinsonian syndromes (PS) and conditions not characterized by nigrostriatal degeneration (non-PS). Results: Data from a total of 303 patients were used in this retrospective analysis. Posterior putamen of the more affected hemisphere (MAH) was shown to be an accurate single-variable predictor for both DLB and PS and was comparable to the most accurate multi-variable models. Conclusions: Automated quantification with DaTQUANT can accurately aid in the differentiation of DLB from non-DLB dementias and PS from non-PS. Optimal thresholds for assisting a diagnosis of DLB are striatal binding ratio (SBR) ≤ 0.65, z-score ≤ −2.36, and a percent deviation ≤ −0.54 for the posterior putamen of the MAH. Optimal posterior putamen thresholds for assisting a diagnosis of PS are SBR ≤ 0.92, z-score ≤ −1.53, and a percent deviation ≤ −0.33, which are similar to our previously reported posterior putamen threshold values using a blended patient pool from multiple study populations. [ABSTRACT FROM AUTHOR]

Purpose: [123I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous injection, [123I]I-FP-CIT is metabolized for a small part by the enzyme CYP3A4, leading to the formation of [123I]I-nor-β-CIT. [123I]I-nor-β-CIT passes the blood-brain barrier and has a very high affinity for the serotonin transporter (SERT). The SERT is expressed in the striatum and cortical areas. So, at least theoretical, the use of frequently used CYP3A4 inhibitors (like amiodarone) may influence the specific to non-specific striatal [123I]I-FP-CIT ratio. Here we tested this novel hypothesis. Methods: Using a retrospective design, we determined the specific to non-specific striatal [123I]I-FP-CIT ratio (using BRASS software) in 6 subjects that were using an CYP3A4 inhibitor and 18 matched controls. Only subjects were included with a normal rated [123I]I-FP-CIT SPECT scan, and all participants were scanned on the same brain-dedicated SPECT system. Results: The specific to non-specific (assessed in the occipital cortex) striatal [123I]I-FP-CIT binding ratio was significantly higher in CYP3A4 users than in the control group (3.52 ± 0.33 vs. 2.90 ± 0.78, p < 0.001). Conclusion: Our preliminary data suggest that the use of CYP3A4 inhibitors may influence striatal [123I]I-FP-CIT binding ratios. This information, when reproduced in larger studies, may be relevant for studies in which quantification of [123I]I-FP-CIT SPECT imaging is used for diagnostic or research purposes. [ABSTRACT FROM AUTHOR]

IntroductionDifferential diagnosis of rest tremor (RT) disorders is challenging, often requiring 123I-ioflupane single-photon-emission-computed tomography (DaTscan), an expensive technique not available worldwide. In the current study, we investigated the performance of a new wearable mobile device termed “RT-ring” in predicting DaTscan result in patients presenting with RT based on rest tremor inertial features.MethodsConsecutive RT patients underwent RT-ring tremor analysis, surface electromyography (sEMG), and DaTscan. The RT-ring is a miniaturized mobile device that uses machine learning based on inertial tremor data to estimate the RT pattern. This electrophysiologic tremor feature has proven to accurately predict DaTscan result. The primary outcome was the RT-ring’s performance in distinguishing patients with and without striatal dopaminergic deficit.ResultsSixty-seven RT patients were enrolled, including 42 patients with striatal dopaminergic deficit and 25 with normal DaTscan. The RT-ring showed 85.0% sensitivity, 90.9% specificity, and 87.9% balanced accuracy in predicting DaTscan result, and demonstrated 96.8% agreement with sEMG in RT pattern classification.ConclusionThe RT-ring is a promising, non-invasive, user-friendly, wearable mobile device for supporting the diagnosis of tremulous Parkinson’s disease in primary care settings, especially in low-income countries with limited access to dopamine imaging.

Background: Phenotypes of CANVAS are increasingly diversified, including bradykinesia and dysautonomia, so that its primary differential diagnoses are multiple system atrophy‐cerebellar type (MSA‐c), and spinocerebellar ataxia type 3 (SCA3). This case series aims to highlight key molecular imaging findings in CANVAS. Cases: We report a case series of six patients with CANVAS who underwent nuclear medicine examinations in our center and 13 patients from the literature. These include 18F‐FDG brain positron emission tomography (PET), single photon emission computed tomography (SPECT) of dopamine transporter (DaT) activity, and 123I‐MIBG cardiac scintigraphy of noradrenergic transmission. Conclusions: In CANVAS, 18F‐FDG brain PET mainly shows cerebellar hypometabolism, with preserved brainstem and striatum metabolism, contrasting with SCA3 and MSA‐c. Dopaminergic denervation on scintigraphy seems to be associated with clinical parkinsonism, ranging from normal to severely impaired DaT SPECT. Additionally, 123I‐MIBG cardiac scintigraphy might show denervation in CANVAS, similar to SCA3, but not in most MSA‐c patients. [ABSTRACT FROM AUTHOR]

Background: As the diagnosis of Parkinson's disease (PD) is fundamentally clinical, the usefulness of ioflupane (123I) single‐photon emission computed tomography (SPECT) or DaTSCAN as a diagnostic tool has been a matter of debate for years. The performance of DaTSCAN is generally recommended in the follow‐up of patients with a clinically uncertain diagnosis, especially in those with a suspected essential tremor, drug‐induced parkinsonism, or vascular parkinsonism. However, there is a dearth of DaTSCAN findings regarding neurodegenerative parkinsonisms besides PD and atypical parkinsonisms. To date, a specific nigrostriatal dopamine uptake pattern that would help differentiate PD from the most frequent atypical parkinsonisms is yet to be described. This fact is further complicated by the possible visualization of abnormalities in the uptake pattern in patients with rarer neurodegenerative parkinsonisms. Objectives: We aimed to summarize the current literature regarding DaTSCAN findings in patients with rare neurodegenerative parkinsonisms. Methods: The PubMed database was systematically screened for studies in English or Spanish up to October 15, 2023, using search terms "DaTSCAN", "ioflupane", "DaT‐SPECT", "123I‐FP‐CIT SPECT", "dopamine transporter imaging", and "[123I] FP‐CIT SPECT". Duplicated publications and studies regarding PD, atypical parkinsonisms, dystonia‐parkinsonism, essential tremor, and parkinsonism due to non‐degenerative causes were excluded. Results: The obtained results were reviewed and summarized, including DaTSCAN findings in fragile X‐associated tremor/ataxia syndrome, prion diseases, Huntington's disease, spinocerebellar ataxia, hereditary spastic paraparesis, metabolic disorders, and other diseases (anti‐IgLON5 disease, ring chromosome 20 syndrome, chorea‐acanthocytosis, and neuronal ceroid lipofuscinosis). Conclusions: This review highlights the need to determine in the future the utility and cost‐effectiveness of DaTSCAN, both as a diagnostic and a prognostic tool, in patients with parkinsonian symptoms in rare neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Diagnosing Dementia with Lewy Bodies (DLB) remains a challenge in clinical practice. The use of 123I-ioflupane (DaTscan™) SPECT imaging, which detects reduced dopamine transporter (DAT) uptake--a key biomarker in DLB diagnosis--could improve diagnostic accuracy. However, DAT imaging is underutilized despite its potential, contributing to delays and suboptimal patient management. Methods: This review evaluates DLB diagnostic practices and challenges faced within the U.S. by synthesizing information from current literature, consensus guidelines, expert opinions, and recent updates on DaTscan FDA filings. It contrasts DAT SPECT with alternative biomarkers, provides recommendations for when DAT SPECT imaging may be indicated and discusses the potential of emerging biomarkers in enhancing diagnostic approaches. Results: The radiopharmaceutical 123I-ioflupane for SPECT imaging was initially approved in Europe (2000) and later in the US (2011) for Parkinsonism/Essential Tremor. Its application was extended in 2022 to include the diagnosis of DLB. DaTscan's diagnostic efficacy for DLB, with its sensitivity, specificity, and predictive values, confirms its clinical utility. However, US implementation faces challenges such as insurance barriers, costs, access issues, and regional availability disparities. Conclusion: 123I-ioflupane SPECT Imaging is indicated for DLB diagnosis and differential diagnosis of Alzheimer's Disease, particularly in uncertain cases. Addressing diagnostic obstacles and enhancing physician-patient education could improve and expedite DLB diagnosis. Collaborative efforts among neurologists, geriatric psychiatrists, psychologists, and memory clinic staff are key to increasing diagnostic accuracy and care in DLB management. [ABSTRACT FROM AUTHOR]

Background and purpose: Pure autonomic failure (PAF) is a rare progressive neurodegenerative disease characterized by neurogenic orthostatic hypotension at presentation, without other neurological abnormalities. Some patients may develop other central neurological features indicative of multiple system atrophy or a Lewy body disorder. There are currently no biomarkers to assess possible central nervous system involvement in probable PAF at an early stage. A possibility is to evaluate the nigrostriatal dopaminergic degeneration by imaging of dopamine transporter with DaTscan brain imaging. The objective was to evaluate subclinical central nervous system involvement using DaTscan in PAF. Methods: We retreospectively reviewed pure autonomic failure patients who were evaluated at the Autonomic Unit between January 2015 and August 2021 and underwent comprehensive autonomic assessment, neurological examination, brain magnetic resonance imaging and DaTscan imaging. DaTscan imaging was performed if patients presented with atypical features which did not meet the criteria for Parkinson's disease or multiple system atrophy or other atypical parkinsonism. Results: In this cohort, the median age was 49.5 years at disease onset, 57.5 years at presentation, and the median disease duration was 7.5 years. Five of 10 patients had an abnormal DaTscan without neurological features meeting the criteria of an alternative diagnosis. Patients with abnormal DaTscan were predominantly males, had shorter disease duration and had more severe genitourinary symptoms. Discussion: Degeneration of nigrostriatal dopaminergic neurons measured using DaTscan imaging can present in patients with PAF without concurrent signs indicating progression to widespread α‐synucleinopathy. It is advocated that DaTscan imaging should be considered as part of the workup of patients with emerging autonomic failure who are considered to have PAF. [ABSTRACT FROM AUTHOR]

BackgroundInvestigation of sex-related motor and non-motor differences and biological markers in Parkinson's disease (PD) may improve precision medicine approach.ObjectiveTo examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD.MethodsWe compared 5-year longitudinal changes in de novo, untreated PD men and women (at baseline N = 423; 65.5%male) of the Parkinson's Progression Markers Initiative (PPMI), assessing motor and non-motor manifestations of disease; and biologic measures in cerebrospinal fluid (CSF) and dopamine transporter deficit on DaTscanTM uptake.ResultsMen experienced greater longitudinal decline in self-reported motor (p

Abstract Aim [123I]Ioflupane (DaTSCAN) has a high binding affinity to the dopamine (DA) transporter (DaT) and tenfold less affinity to serotonin (5-HT) transporter (SERT). Both neurotransmitters are considered to contribute to body weight regulation. This study assesses the association between body mass index (BMI) and DaTSCAN availability in brain. Method Scans from 74 consecutive patients who had undergone DaTSCAN single-photon emission computed tomography–computed tomography (SPECT-CT) were used to obtain semi- and absolute quantitative data in several volumes of interest (VOIs). Relative semi-quantitative specific binding ratios (SBRs) from Chang attenuated SPECT were obtained from GE DaTQUANT. Absolute normalised concentration (NC) was calculated from attenuation/scatter corrected SPECT-CT images, using an adapted version of the EARL Ltd (European Association of Nuclear Medicine (EANM) Research 4 Life) template. Scans were subdivided into either degenerative parkinsonism (abnormal = 49), borderline (n = 14) or scan without evidence of dopaminergic deficit (SWEDD = 11) using visual assessment and SBR values by two nuclear medicine consultants. Results SBRs did not correlate with BMI. However, NC values correlated negatively in the entire cohort, with the strongest correlation in the frontal (r = − 0.649. p = 0.000), occipital (r = − 0.555, p = 0.000) regions and pons (r = − 0.555, p = 0.000). In the abnormal (n = 49) and SWEDD group (n = 11), NC of the frontal region was the most correlated with BMI (r = − 0.570, p = 0.000; r = − 0.813, p = 0.002, respectively). In the borderline group (n = 14), the left posterior putamen displayed the strongest correlation (r = − 0.765, p = 0.001). Conclusion Absolute NC values demonstrate a strong inverse correlation with BMI, strongest in the extrastriatal regions. Due to the predominately non-overlapping distribution of DaT and SERT, this study suggests greater involvement of SERT in obesity with possible interplay with DA transmission.

BackgroundDiagnosing Dementia with Lewy Bodies (DLB) remains a challenge in clinical practice. The use of 123I-ioflupane (DaTscan™) SPECT imaging, which detects reduced dopamine transporter (DAT) uptake—a key biomarker in DLB diagnosis—could improve diagnostic accuracy. However, DAT imaging is underutilized despite its potential, contributing to delays and suboptimal patient management.MethodsThis review evaluates DLB diagnostic practices and challenges faced within the U.S. by synthesizing information from current literature, consensus guidelines, expert opinions, and recent updates on DaTscan FDA filings. It contrasts DAT SPECT with alternative biomarkers, provides recommendations for when DAT SPECT imaging may be indicated and discusses the potential of emerging biomarkers in enhancing diagnostic approaches.ResultsThe radiopharmaceutical 123I-ioflupane for SPECT imaging was initially approved in Europe (2000) and later in the US (2011) for Parkinsonism/Essential Tremor. Its application was extended in 2022 to include the diagnosis of DLB. DaTscan’s diagnostic efficacy for DLB, with its sensitivity, specificity, and predictive values, confirms its clinical utility. However, US implementation faces challenges such as insurance barriers, costs, access issues, and regional availability disparities.Conclusion123I-ioflupane SPECT Imaging is indicated for DLB diagnosis and differential diagnosis of Alzheimer’s Disease, particularly in uncertain cases. Addressing diagnostic obstacles and enhancing physician-patient education could improve and expedite DLB diagnosis. Collaborative efforts among neurologists, geriatric psychiatrists, psychologists, and memory clinic staff are key to increasing diagnostic accuracy and care in DLB management.

Aim: [123I]Ioflupane (DaTSCAN) has a high binding affinity to the dopamine (DA) transporter (DaT) and tenfold less affinity to serotonin (5-HT) transporter (SERT). Both neurotransmitters are considered to contribute to body weight regulation. This study assesses the association between body mass index (BMI) and DaTSCAN availability in brain. Method: Scans from 74 consecutive patients who had undergone DaTSCAN single-photon emission computed tomography–computed tomography (SPECT-CT) were used to obtain semi- and absolute quantitative data in several volumes of interest (VOIs). Relative semi-quantitative specific binding ratios (SBRs) from Chang attenuated SPECT were obtained from GE DaTQUANT. Absolute normalised concentration (NC) was calculated from attenuation/scatter corrected SPECT-CT images, using an adapted version of the EARL Ltd (European Association of Nuclear Medicine (EANM) Research 4 Life) template. Scans were subdivided into either degenerative parkinsonism (abnormal = 49), borderline (n = 14) or scan without evidence of dopaminergic deficit (SWEDD = 11) using visual assessment and SBR values by two nuclear medicine consultants. Results: SBRs did not correlate with BMI. However, NC values correlated negatively in the entire cohort, with the strongest correlation in the frontal (r = − 0.649. p = 0.000), occipital (r = − 0.555, p = 0.000) regions and pons (r = − 0.555, p = 0.000). In the abnormal (n = 49) and SWEDD group (n = 11), NC of the frontal region was the most correlated with BMI (r = − 0.570, p = 0.000; r = − 0.813, p = 0.002, respectively). In the borderline group (n = 14), the left posterior putamen displayed the strongest correlation (r = − 0.765, p = 0.001). Conclusion: Absolute NC values demonstrate a strong inverse correlation with BMI, strongest in the extrastriatal regions. Due to the predominately non-overlapping distribution of DaT and SERT, this study suggests greater involvement of SERT in obesity with possible interplay with DA transmission. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurological disease that produces uncontrollable movements and a variety of other symptoms. It can be difficult to make an accurate PD diagnosis since the signs and symptoms, especially early on, might be mistaken for other medical diseases or physiological changes associated with normal aging. This research proposed novel technique in predicting PD based on dopamine transporter scan (DaTscan) images of brain using deep learning techniques. Here the aim is to collect the historical data and live DaTscan image of patients with symptoms of PD and predict disease. Initially input data have been pre-processed for image resize, noise removal and smoothening. Then the processed image has been selected based on their features using kernel-based deep convolution neural network (KDCNN). The selected deep features have been classified using reinforcement Q-learning-based neural networks (RQLNNs) to predict the presence of PD. Here experimental results show feature-selected and classified output of DaTscan brain image using the proposed model. For MRI image dataset, the proposed technique obtained accuracy of 97.5%, precision of 93%, recall of 82% and F-1 score of 87%. The proposed technique obtained accuracy of 98%, precision of 93%, recall of 80% and F-1 score of 88% for DaTscan dataset. [ABSTRACT FROM AUTHOR]

Background: Genetic risk factors impact around 15% of Parkinson's disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative‐based data, various studies have been published on GBA‐PD cohorts which suggested possible differences in dopaminergic nigrostriatal denervation pattern, particularly in caudate and putamen nuclei. Methods: This retrospective study included two consecutive homogenous cohorts of GBA‐PD and idiopathic (I‐PD) patients. Each consecutive GBA‐PD patient has been matched with a 1:1 pairing method with a consecutive I‐PD subject according to age, age at disease onset, sex, Hoehn & Yahr (H&Y) staging scale and comorbidity level (CCI). Semiquantitative volumetric data by the DaTQUANTTM software integrated in the DaTSCAN exam performed at time of the diagnosis (SPECT imaging performed according to current guidelines of I‐123 FPCIT SPECT imaging) were extrapolated. Bilateral specific binding ratios (SBR) at putamen and caudate levels were calculated, using the occipital lobes uptake. The Mann–Whitney test was performed to compare the two cohorts while the Spearman's test was used to find correlations between motor and volumetric data in each group. Bonferroni correction was used to account for multiple comparisons. Results: Two cohorts of 25 patients each (GBA‐PD and I‐PD), were included. By comparing GBA‐PD and I‐PD patients, lower SBR values were found in the most affected anterior putamen and left caudate of the GBA‐PD cohort. Furthermore, in the GBA‐PD cohort the SBR of the most affected posterior putamen negatively correlated with the H&Y scale. However, none of these differences or correlations remained significant after Bonferroni correction for multiple comparisons. Conclusions: We observed differences in SBR values in GBA‐PD patients compared with I‐PD. However, these differences were no longer significant after Bonferroni multiple comparisons correction highlighting the need for larger, longitudinal studies. [ABSTRACT FROM AUTHOR]

Purpose: In routine practice, dopamine transporter (DAT) imaging is frequently used as a diagnostic tool to support the diagnosis of Parkinson's disease or dementia with Lewy bodies. In 2008, we published a review on which medications and drugs of abuse may influence striatal [123I]I-FP-CIT binding and consequently may influence the visual read of an [123I]I-FP-CIT SPECT scan. We made recommendations on which drugs should be withdrawn before performing DAT imaging in routine practice. Here, we provide an update of the original work based on published research since 2008. Methods: We performed a systematic review of literature without language restriction from January 2008 until November 2022 to evaluate the possible effects of medications and drugs of abuse, including the use of tobacco and alcohol, on striatal DAT binding in humans. Results: The systematic literature search identified 838 unique publications, of which 44 clinical studies were selected. Using this approach, we found additional evidence to support our original recommendations as well as some new findings on potential effect of other medications on striatal DAT binding. Consequently, we updated the list of medications and drugs of abuse that may influence the visual read of [123I]I-FP-CIT SPECT scans in routine clinical practice. Conclusion: We expect that a timely withdrawal of these medications and drugs of abuse before DAT imaging may reduce the incidence of false-positive reporting. Nevertheless, the decision to withdraw any medication must be made by the specialist in charge of the patient's care and considering the pros and cons of doing so. [ABSTRACT FROM AUTHOR]

Introduction: Dopaminergic scintigraphic imaging is a cornerstone to support the diagnosis in dementia with Lewy bodies. To clarify the current state of knowledge on this imaging modality and its impact on clinical diagnosis, we performed an updated systematic review of the literature. Methods: This systematic review was carried out according to PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through June 2022 was performed using the following search algorithm: (a) "Lewy body" [TI] OR "Lewy bodies" [TI] and (b) ("DaTscan" OR "ioflupane" OR "123ip" OR "123?ip" OR "123 ip" OR "123i-FP-CIT" OR "FPCIT" OR "FP-CIT" OR "beta?CIT" OR "beta CIT" OR "CIT?SPECT" OR "CIT SPECT" OR "Dat?scan*" OR "dat scan*" OR "dat?spect*" OR "SPECT"). Risk of bias and applicability concerns of the studies were evaluated using the QUADAS-2 tool. Results: We performed a qualitative analysis of 59 studies. Of the 59 studies, 19 (32%) addressed the diagnostic performance of dopamine transporter imaging, 15 (25%) assessed the identification of dementia with Lewy bodies in the spectrum of Lewy body disease and 18 (31%) investigated the role of functional dopaminergic imaging in distinguishing dementia with Lewy bodies from other dementias. Dopamine transporter loss was correlated with clinical outcomes in 19 studies (32%) and with other functional imaging modalities in 15 studies (25%). Heterogeneous technical aspects were found among the studies through the use of various radioligands, the more prevalent being the [123I]N‑ω‑fluoropropyl‑2β‑carbomethoxy‑3β‑(4‑iodophenyl) nortropane (123I-FP-CIT) in 54 studies (91.5%). Image analysis used visual analysis (9 studies, 15%), semi-quantitative analysis (29 studies, 49%), or a combination of both (16 studies, 27%). Conclusion: Our systematic review confirms the major role of dopaminergic scintigraphic imaging in the assessment of dementia with Lewy bodies. Early diagnosis could be facilitated by identifying the prodromes of dementia with Lewy bodies using dopaminergic scintigraphic imaging coupled with emphasis on clinical neuropsychiatric symptoms. Most published studies use a semi-quantitative analytical assessment of tracer uptake, while there are no studies using quantitative analytical methods to measure dopamine transporter loss. The superiority of a purely quantitative approach to assess dopaminergic transmission more accurately needs to be further clarified. [ABSTRACT FROM AUTHOR]

Background: A hallmark of Parkinson's disease (PD) is progressive loss of dopamine terminals in the basal ganglia, with clinical symptoms including motor and non‐motor manifestations such as bradykinesia, rigidity, and cognitive impairment. Dopamine transporter single‐photon emission computed tomography (DaT‐SPECT) can be used to assess dopaminergic denervation by detecting loss of striatal dopamine transporters (DaT). Objective: We examined DaT binding scores' (DaTbs) association with motor outcomes in PD and explored its usefulness as a predictor of disease progression. Faster dopaminergic denervation in the basal ganglia was hypothesized to have stronger correlation and predictive value for poor motor outcomes. Methods: Data was analyzed from the Parkinson's Progression Markers Initiative. DaTbs in the putamen and caudate nucleus were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) scores for walking and balance difficulties, gait difficulties, and presence of dyskinesias. A predictive model using baseline speed of drop in DaT binding score was performed for each motor outcome. Results: All motor outcomes had mild, significantly negative correlation with DaTbs in the putamen and caudate nucleus, with similar degree of correlation per region. Speed of drop was predictive of only substantial gait difficulties when evaluated in the putamen but not the caudate. Conclusions: These findings suggest that analyzing speed of drop in DaTbs, which occurs early in the motor phase of the disease, may be helpful for predicting clinical outcomes in PD. Longer observation of this cohort may provide further data to investigate DaTbs as a prognostic marker in PD. [ABSTRACT FROM AUTHOR]

Abstract Background Dopamine transporter (DAT) imaging of striatum is clinically used in Parkinson’s disease (PD) and neurodegenerative parkinsonian syndromes (PS) especially in the early disease stages. The aim of the present study was to evaluate the diagnostic performance of the recently developed tracer for DAT imaging [18F]FE-PE2I PET/CT to the reference standard [123I]FP-CIT SPECT. Methods Ninety-eight unselected patients referred for DAT imaging were included prospectively and consecutively and evaluated with [18F]FE-PE2I PET/CT and [123I]FP-CIT SPECT on two separate days. PET and SPECT scans were categorized independently by two blinded expert readers as either normal, vascular changes, or mixed. Semiquantitative values were obtained for each modality and compared regarding effect size using Glass’ delta. Results Fifty-six of the [123I]FP-CIT SPECT scans were considered abnormal (52 caused by PS, 4 by infarctions). Using [18F]FE-PE2I PET/CT, 95 of the 98 patients were categorized identically to SPECT as PS or non-PS with a sensitivity of 0.94 [0.84–0.99] and a specificity of 1.00 [0.92–1.00]. Inter-reader agreement for [18F]FE-PE2I PET with a kappa of 0.97 [0.89–1.00] was comparable to the agreement for [123I]FP-CIT SPECT of 0.96 [0.76–1.00]. Semiquantitative values for short 10-min reconstructions of [18F]FE-PE2I PET/CT were comparable to longer reconstructions. The effect size for putamen/caudate nucleus ratio was significantly increased using PET compared to SPECT. Conclusions The high correspondence of [18F]FE-PE2I PET compared to reference standard [123I]FP-CIT SPECT establishes [18F]FE-PE2I PET as a feasible PET tracer for clinical use with favourable scan logistics.

Background: Task specific tremor (TST) is a poorly understood entity without any standard treatments, that may subsequently develop tremor during additional tasks, later develop postural/kinetic tremor (essential tremor criteria), and later develop Parkinson's disease. The pathophysiology is not understood as it has features of tremor, dystonia, and parkinsonism. Objectives: To assess response of TST to apomorphine and thus infer pathophysiology. Methods: We administered sublingual apomorphine to 8 patients diagnosed with Parkinson's disease based on clinical criteria and dopamine imaging, who all initially presented with TST and later presented other parkinsonian signs and dopamine imaging deficits. Results: Apomorphine improved TST, which was refractory to oral levodopa and other tremor therapies, in 6/8 subjects. Discussion: These results offer a treatment option for TST, which is usually refractory to other pharmacologic treatments, in patients with other parkinsonian features, and infers a dopaminergic pathophysiology of TST. [ABSTRACT FROM AUTHOR]

Background: Dopamine transporter (DAT) imaging of striatum is clinically used in Parkinson's disease (PD) and neurodegenerative parkinsonian syndromes (PS) especially in the early disease stages. The aim of the present study was to evaluate the diagnostic performance of the recently developed tracer for DAT imaging [18F]FE-PE2I PET/CT to the reference standard [123I]FP-CIT SPECT. Methods: Ninety-eight unselected patients referred for DAT imaging were included prospectively and consecutively and evaluated with [18F]FE-PE2I PET/CT and [123I]FP-CIT SPECT on two separate days. PET and SPECT scans were categorized independently by two blinded expert readers as either normal, vascular changes, or mixed. Semiquantitative values were obtained for each modality and compared regarding effect size using Glass' delta. Results: Fifty-six of the [123I]FP-CIT SPECT scans were considered abnormal (52 caused by PS, 4 by infarctions). Using [18F]FE-PE2I PET/CT, 95 of the 98 patients were categorized identically to SPECT as PS or non-PS with a sensitivity of 0.94 [0.84–0.99] and a specificity of 1.00 [0.92–1.00]. Inter-reader agreement for [18F]FE-PE2I PET with a kappa of 0.97 [0.89–1.00] was comparable to the agreement for [123I]FP-CIT SPECT of 0.96 [0.76–1.00]. Semiquantitative values for short 10-min reconstructions of [18F]FE-PE2I PET/CT were comparable to longer reconstructions. The effect size for putamen/caudate nucleus ratio was significantly increased using PET compared to SPECT. Conclusions: The high correspondence of [18F]FE-PE2I PET compared to reference standard [123I]FP-CIT SPECT establishes [18F]FE-PE2I PET as a feasible PET tracer for clinical use with favourable scan logistics. [ABSTRACT FROM AUTHOR]

Our patient had a symptomatic AC that underwent fenestration with complete resolution of her symptoms. Due to the severity of the symptoms, the patient underwent neurosurgical intervention with AC fenestration. Keywords: tremor; Holmes; arachnoid cyst; neurosurgery; MRI; DATScan EN tremor Holmes arachnoid cyst neurosurgery MRI DATScan 998 1000 3 06/20/23 20230601 NES 230601 Arachnoid cyst (AC) is a fluid-filled malformation of the arachnoid tissue.[1] Congenital, genetic, and traumatic factors have been suggested as the underlying mechanisms. [Extracted from the article]

Abstract Background Diagnosis of Parkinson’s disease (PD) is informed by the presence of progressive motor and non-motor symptoms and by imaging dopamine transporter with [123I]ioflupane (DaTscan). Deep learning and ensemble methods have recently shown promise in medical image analysis. Therefore, this study aimed to develop a three-stage, deep learning, ensemble approach for prognosis in patients with PD. Methods Retrospective data of 198 patients with PD were retrieved from the Parkinson’s Progression Markers Initiative database and randomly partitioned into the training, validation, and test sets with 118, 40, and 40 patients, respectively. The first and second stages of the approach extracted features from DaTscan and clinical measures of motor symptoms, respectively. The third stage trained an ensemble of deep neural networks on different subsets of the extracted features to predict patient outcome 4 years after initial baseline screening. The approach was evaluated by assessing mean absolute percentage error (MAPE), mean absolute error (MAE), Pearson’s correlation coefficient, and bias between the predicted and observed motor outcome scores. The approach was compared to individual networks given different data subsets as inputs. Results The ensemble approach yielded a MAPE of 18.36%, MAE of 4.70, a Pearson’s correlation coefficient of 0.84, and had no significant bias indicating accurate outcome prediction. The approach outperformed individual networks not given DaTscan imaging or clinical measures of motor symptoms as inputs, respectively. Conclusion The approach showed promise for longitudinal prognostication in PD and demonstrated the synergy of imaging and non-imaging information for the prediction task.

Keywords: -galactosidase; DaTscan; GLB1; lysosomal storage disorder; nigrostriatal degeneration EN -galactosidase DaTscan GLB1 lysosomal storage disorder nigrostriatal degeneration 825 828 4 08/05/22 20220801 NES 220801 GM1-gangliosidosis is a rare lysosomal storage disorder caused by biallelic I GLB1 i variants leading to -galactosidase deficiency.1,2 Level of residual enzymatic activity at least partly explains its phenotypic heterogeneity, including variability in age at symptom onset, clinical severity, and progression rate.1-3 Three phenotypes are described, including infantile-onset (type I) and late infantile/juvenile-onset (type II) forms, which are lethal in early childhood, and late-onset form (type III), which manifests between late childhood and the third decade.1,2 GM1-gangliosidosis type III, whose milder phenotype usually permits survival into adulthood,2 manifests as a complex syndrome featuring skeletal dysplasia, corneal opacities, progressive generalized dystonia with prominent oromandibular and bulbar involvement, akinetic-rigid parkinsonism, and cognitive decline in later stages.1 Despite neuropathology demonstrates selective deposition of glycosphingolipids (ie the substrate of -galactosidase) in the basal ganglia leading to prominent striatal neuronal loss,4,5 in vivo evidence suggesting nigrostriatal degeneration is extremely scant.6 We report abnormal presynaptic dopaminergic imaging and long-term follow-up of a case of GM1-gangliosidosis type III whose genotype and biochemical analysis were previously reported.7 Case Report A 32-year-old White British female was born prematurely at 32 gestational weeks. Abnormal DaTscan in GM1-Gangliosidosis Type III Manifesting with Dystonia-Parkinsonism. [Extracted from the article]

Background: Parkinsonian syndrome (PS) is a broad category of neurodegenerative movement disorders that includes Parkinson disease, multiple system atrophy (MSA), progressive supranuclear palsy, and corticobasal degeneration. Parkinson disease (PD) is the second most common neurodegenerative disorder with loss of dopaminergic neurons of the substantia nigra and, thus, dysfunction of the nigrostriatal pathway. In addition to the motor symptoms of bradykinesia, rigidity, tremors, and postural instability, nonmotor symptoms such as autonomic dysregulation (AutD) can also occur. Heart rate variability (HRV) has been used as a measure of AutD and has shown to be prognostic in diseases such as diabetes mellitus and cirrhosis, as well as PD. I-123 ioflupane, a gamma ray-emitting radiopharmaceutical used in single-photon emission computed tomography (SPECT), is used to measure the loss of dopaminergic neurons in PD. Through the combination of SPECT and HRV, we tested the hypothesis that asymmetrically worse left-sided neuronal loss would cause greater AutD. Methods: 51 patients were enrolled on the day of their standard of care I-123 ioflupane scan for the work-up of possible Parkinsonian syndrome. Demographic information, medical and medication history, and ECG data were collected. HRV metrics were extracted from the ECG data. I-123 ioflupane scans were interpreted by a board-certified nuclear radiologist and quantified by automated software to generate striatal binding ratios (SBRs). Statistical analyses were performed to find correlations between the HRV and SPECT parameters. Results: 32 patients were excluded from the final analysis because of normal scans, prior strokes, cardiac disorders and procedures, or cancer. Abnormal I-123 ioflupane scans were clustered using T-SNE, and one-way ANOVA was performed to compare HRV and SBR parameters. The analysis was repeated after the exclusion of patients taking angiotensin-converting enzyme inhibitors, given the known mechanism on autonomic function. Subsequent analysis showed a significant difference between the high-frequency domains of heart rate variability, asymmetry of the caudate SBR, and putamen-to-caudate SBR. Conclusion: Our results support the hypothesis that more imbalanced (specifically worse left-sided) neuronal loss results in greater AutD. [ABSTRACT FROM AUTHOR]

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Objective: This study aimed to determine the prevalence and clinical features of Parkinson's disease (PD)/PD dementia (PD/PDD) or dementia with Lewy bodies (DLB) in idiopathic normal pressure hydrocephalus (iNPH). Methods: Patients with iNPH who were admitted to the Department of Neurology, Juntendo University School of Medicine over the past 10 years have been retrospectively analyzed. The diagnosis of iNPH and concomitant PD/PDD or DLB was established using diagnostic criteria. Motor symptoms were assessed by the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III. 123I-ioflupane single-photon emission computed tomography (DaT-SPECT) and cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC)-based assay were performed for alpha synuclein aggregation. Results: Overall, 79 patients met the criteria for iNPH, of which 34 developed iNPH without accompanying disorders (iNPHa; 43%), 23 developed iNPH with comorbid PD/PDD (iNPHc + PD/PDD; 29.1%), and 8 developed iNPH with comorbid DLB (iNPHc + DLB; 10.1%). Significant differences in facial expansion and upper-limb parkinsonism were observed with a comorbidity of either PD/PDD or DLB. The specific binding ratio (SBR) of DaTscan was reduced in iNPHa (p = 0.02), but it reduced further with comorbid PD/PDD (p < 0.01) or DLB (p < 0.01). RT-QuIC was positive for all 13 comorbid PD/PDD and negative for all 19 iNPHa. Conclusion: These results highlight that synucleinopathies coexist with iNPH. These can be differentiated by performing DaTscan and RT-QuIC, which can affect its clinical features. [ABSTRACT FROM AUTHOR]

Background: Quantitative thresholds are helpful to define an abnormal DaT SPECT in patients with suspected nigrostriatal degenerative diseases (NSDD). The optimal DaTQUANT threshold for diagnostic accuracy of DaT SPECT across combined movement and cognitive disorder populations has been previously described. Methods : We established optimal DaTQUANT thresholds that enhance the discrimination between dementia with Lewy bodies (DLB) and non-DLB dementia types, as well as between Parkinsonian syndromes (PS) and conditions not characterized by nigrostriatal degeneration (non-PS). Results: Data from a total of 303 patients were used in this retrospective analysis. Posterior putamen of the more affected hemisphere (MAH) was shown to be an accurate single-variable predictor for both DLB and PS and was comparable to the most accurate multi-variable models. Conclusions: Automated quantification with DaTQUANT can accurately aid in the differentiation of DLB from non-DLB dementias and PS from non-PS. Optimal thresholds for assisting a diagnosis of DLB are striatal binding ratio (SBR) ≤ 0.65, z-score ≤ -2.36, and a percent deviation ≤ -0.54 for the posterior putamen of the MAH. Optimal posterior putamen thresholds for assisting a diagnosis of PS are SBR ≤ 0.92, z-score ≤ -1.53, and a percent deviation ≤ -0.33, which are similar to our previously reported posterior putamen threshold values using a blended patient pool from multiple study populations.

PSP-Like Phenotype in Genetically Confirmed SCA12 Keywords: SCA12; PSP; atypical parkinsonism; DaTSCAN EN SCA12 PSP atypical parkinsonism DaTSCAN 326 328 3 02/23/23 20230201 NES 230201 Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansions in the protein phosphatase 2 regulatory subunit B beta (PPP2R2B) gene in chromosome 5q.[1] The prevalence of SCA12 is high in Northern parts of India because of the common founder effect, and most of the affected families belong to the Agrawal community.[2] The commonest presenting symptom of SCA12 is the action tremors of upper limbs, which may precede the ataxia by many years.[[3]] Phenotypic spectrum of SCA12 also includes various non-ataxic manifestations, such as dystonia, parkinsonism, and cognitive impairment.[[1], [3]] Rarely, SCA12 can present as an "atypical atypical parkinsonism" and pose a diagnostic challenge.[5] A 61-year-old man from Punjab, India, presented with a history of progressive difficulty in walking, which worsened over the past 3 years with episodes of frequent falls. One should consider SCA12 in the differential diagnosis of atypical atypical parkinsonism with a PSP-like phenotype in a patient of ethnic origin where SCA12 is prevalent, even in the absence of family history. [Extracted from the article]

Herein, we present a rare patient with hereditary spastic paraparesis (HSP) in whom significant parkinsonism was involved in the clinic. Besides, the dopamine transport single-photon emission computed tomography scan also showed decreased tracer uptake in the bilateral striatum. Via the presentation of this patient, we discuss the parkinsonian findings in patients with HSP. We think that the observations of dopaminergic neuron vulnerability in HSP patients raise the possibility that degeneration of central dopaminergic neurons may contribute to the phenotype of HSP. The documentation of these rare variants will aid to understand the unknown pathophysiology of the disease course. [ABSTRACT FROM AUTHOR]

Aims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan). Methods: We retrospectively identified 47 patients (17 Alzheimer's dementia, 10 idiopathic Parkinson's disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores. Results: DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right p < 0.01, putamen right p < 0.05, left p < 0.05) and between pNfH and putamen (right p < 0.05; left p < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results. Conclusion: We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases. [ABSTRACT FROM AUTHOR]

Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms. [ABSTRACT FROM AUTHOR]

Aims: Neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) are biomarkers for neuroaxonal damage. We assessed whether NfL and other biomarker levels in the CSF are correlated to the loss of presynaptic dopamine transporters in neurons as detected with dopamine transporter SPECT (DaTscan).Methods: We retrospectively identified 47 patients (17 Alzheimer’s dementia, 10 idiopathic Parkinson’s disease, 7 Lewy body dementia, 13 progressive supranuclear palsy or corticobasal degeneration) who received a DaTscan and a lumbar puncture. DaTscan imaging was performed according to current guidelines, and z-scores indicating the decrease in uptake were software based calculated for the nucleus caudatus and putamen. The CSF biomarkers progranulin, total-tau, alpha-synuclein, NfL, and pNfH were correlated with the z-scores.Results: DaTscan results in AD patients did not correlate with any biomarker. Subsuming every movement disorder with nigrostriatal neurodegeneration resulted in a strong correlation between putamen/nucleus caudatus and NfL (nucleus caudatus right p < 0.01, putamen right p < 0.05, left p < 0.05) and between pNfH and putamen (right p < 0.05; left p < 0.042). Subdividing in disease cohorts did not reveal significant correlations. Progranulin, alpha-synuclein, and total-tau did not correlate with DaTscan results.Conclusion: We show a strong correlation of NfL and pNfH with pathological changes in presynaptic dopamine transporter density in the putamen concomitant to nigrostriatal degeneration. This correlation might explain the reported correlation of impaired motor functions in PD and NfL as seen before, despite the pathological heterogeneity of these diseases.

Introduction. Neuroimaging plays an increasingly important role in the diagnosis of parkinsonian syndromes. Aim of the study. In this paper, the authors elaborate on the necessity of using magnetic resonance imaging (MRI) in Parkinson’s Disease (PD) and its potential role in differential diagnosis versus other neurodegenerative parkinsonian syndromes such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal syndrome. State of the art. The currently known characteristic abnormalities are listed and tabulated, current recommendations are sum- marised and sample images are provided. As routine MRI scanning in PD remains controversial, the authors’ aim is to show the pros and cons in clinical practice. Additionally, the rationale for functional imaging examination, including [ 123I]-FP-CIT SPECT (DaTSCAN) and [99mTc]- HMPAO-SPECT, [18F]-FDG-PET, [123I]-mIBG-SPECT is discussed. Clinical vignette. This paper is accompanied by two illustrative clinical cases in which neuroimaging studies played a key role in diagnosis and further management. Conclusions. Neuroimaging can be helpful in differentiating PD from both atypical and symptomatic parkinsonism. Nevertheless, extensive neurological assessment in a majority of PD cases is sufficient to make a diagnosis. A network of specialists in movement disorders should be established in order to enable better, faster and more precise diagnosis of parkinsonism. [ABSTRACT FROM AUTHOR]

Background: Even though a significant fraction of Parkinson's disease (PD) patients presents with only minor or no motor asymmetry, the motor symptoms in PD typically start on one side of the body and worse symptoms on the side of the disease onset usually persist long after the disease has become clinically bilateral. The asymmetric presentation of PD has been studied over the years, with some studies showing slower progression in PD subjects with asymmetric disease presentation. In other studies, however, it was not possible to relate the asymmetry to disease progression. Objective: The main objective of the present study was to assess the effect of asymmetry at disease onset on disease progression. Methods: Using the data available in the Parkinson's Progression Markers Initiative (PPMI) database, at baseline, 423 subjects with de-novo PD were included in the study. Instead of dichotomizing the subjects in asymmetric and symmetric, we kept the asymmetry index and the non-motor, disability, and motor progression at one-, three-, and five-year follow-up continuous. Pearson's r correlational analysis and the coefficient of determination R2 were used to correlate asymmetry indices and disease progression. Results: There was no correlation between neither clinically, nor DatSCAN defined asymmetry and non-motor, motor, and disability progression in the de-novo PD subjects with a 5-year follow-up. Conclusion: Asymmetry at disease onset does not predict progression of PD. Further studies are needed to investigate whether early detection of asymmetry on clinical grounds could successfully distinguish between PD and symmetric types of atypical parkinsonism in the early stages of the disease. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of Parkinson's disease (PD) is informed by the presence of progressive motor and non-motor symptoms and by imaging dopamine transporter with [123I]ioflupane (DaTscan). Deep learning and ensemble methods have recently shown promise in medical image analysis. Therefore, this study aimed to develop a three-stage, deep learning, ensemble approach for prognosis in patients with PD. Methods: Retrospective data of 198 patients with PD were retrieved from the Parkinson's Progression Markers Initiative database and randomly partitioned into the training, validation, and test sets with 118, 40, and 40 patients, respectively. The first and second stages of the approach extracted features from DaTscan and clinical measures of motor symptoms, respectively. The third stage trained an ensemble of deep neural networks on different subsets of the extracted features to predict patient outcome 4 years after initial baseline screening. The approach was evaluated by assessing mean absolute percentage error (MAPE), mean absolute error (MAE), Pearson's correlation coefficient, and bias between the predicted and observed motor outcome scores. The approach was compared to individual networks given different data subsets as inputs. Results: The ensemble approach yielded a MAPE of 18.36%, MAE of 4.70, a Pearson's correlation coefficient of 0.84, and had no significant bias indicating accurate outcome prediction. The approach outperformed individual networks not given DaTscan imaging or clinical measures of motor symptoms as inputs, respectively. Conclusion: The approach showed promise for longitudinal prognostication in PD and demonstrated the synergy of imaging and non-imaging information for the prediction task. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar disorder (BD) has been suggested to be a risk factor for the development of Parkinson's disease (PD). Standard treatment of BD includes drugs that are known to induce drug-induced parkinsonism (DIP). Clinical differentiation between PD and DIP is crucial and might be aided by functional neuroimaging of the dopaminergic nigrostriatal pathway.Methods: Twenty consecutive BD patients with parkinsonism were clinically assessed and underwent 123I-ioflupane dopamine transporter single-photon emission computer tomography (SPECT). Imaging data of BD patients with pathological scans were further compared to a population of 40 de novo PD patients.Results: Four BD patients had abnormal scans, but their clinical features and cumulative exposure to both antipsychotic drugs and lithium were similar to those of BD patients with normal dopamine transporter imaging. BD patients with pathological scans had putaminal binding ratio and putamen-to-caudate ratios higher than those of PD patients despite a similar motor symptom burden.Conclusions: Up to 20% of BD patients with parkinsonism might have an underlying dopaminergic deficit, which would not be due to cumulative exposure to offending drugs and is ostensibly higher than expected in the general population. This supports the evidence that BD represents a risk factor for subsequent development of neurodegenerative parkinsonism, the nature of which needs to be elucidated.

Objectives: Bipolar disorder (BD) has been suggested to be a risk factor for the development of Parkinson's disease (PD). Standard treatment of BD includes drugs that are known to induce drug-induced parkinsonism (DIP). Clinical differentiation between PD and DIP is crucial and might be aided by functional neuroimaging of the dopaminergic nigrostriatal pathway. Methods: Twenty consecutive BD patients with parkinsonism were clinically assessed and underwent 123I-ioflupane dopamine transporter single-photon emission computer tomography (SPECT). Imaging data of BD patients with pathological scans were further compared to a population of 40 de novo PD patients. Results: Four BD patients had abnormal scans, but their clinical features and cumulative exposure to both antipsychotic drugs and lithium were similar to those of BD patients with normal dopamine transporter imaging. BD patients with pathological scans had putaminal binding ratio and putamen-to-caudate ratios higher than those of PD patients despite a similar motor symptom burden. Conclusions: Up to 20% of BD patients with parkinsonism might have an underlying dopaminergic deficit, which would not be due to cumulative exposure to offending drugs and is ostensibly higher than expected in the general population. This supports the evidence that BD represents a risk factor for subsequent development of neurodegenerative parkinsonism, the nature of which needs to be elucidated. [ABSTRACT FROM AUTHOR]

Aim: Dopamine transporter (DAT) imaging with [123I] FP-CIT (DaTSCAN) is an established diagnostic tool in parkinsonism and dementia. Using a low energy high resolution and sensitivity (LEHRS) collimator and step and shoot continuous scanning mode, Swiftscan single photon emission computed tomography (SPECT) (GE Healthcare) enhances sensitivity and enables time or dose reduction. In this phantom and clinical study, we aim to validate a 25% reduction of the acquisition time using Swiftscan and its lack of effect on visual or quantitative analysis.Methods: Anthropomorphic striatal phantom with fillable striata was used. SPECT data from 30 normals (12 men, 18 women; age range, 39–91 years; mean, 71 years ± 11) and 30 patients with Parkinson disease or other neurodegenerative disease with extra-pyramidal syndrome (16 men, 14 women; age range, 43–84 years; mean, 69 years ± 10) were also included. Both phantom and clinical data were acquired using Swiftscan and reconstructed with full-time and 25%-time reduction. Striatal binding ratios (SBRs) were calculated using DaTQUANT software.Results: Both in phantom experiments and in clinical cases, visual analysis remained stable and SBRs were not significantly different whether using Swiftscan or Swiftscan with 25%-time reduction (p < 0.001). There was an excellent inter-rater agreement and no effect of time reduction on diagnosis or on image quality.Conclusion: Using Swiftscan step and shoot continuous SPECT mode, 25%-time reduction can be applied to DaTSCAN acquisition protocols, without impairing visual or quantitative analysis.

Aim: The second consensus statement for the diagnosis of multiple system atrophy type cerebellar (MSA-C) includes pons and middle cerebellar peduncle (MCP) atrophy as MRI features. However, other MRI abnormalities such as MCP hyperintensity, hot cross bun sign (HCB), putaminal hypointensity and hyperintense putaminal rim have been described. Objectives: To evaluate, in patients with sporadic late-onset cerebellar ataxia (SLOCA), the discriminative value of several MRI features for the diagnosis of MSA-C, to follow their evolution during the course of MSA-C, and to search for correlations between these MRI features and clinical signs. Methods: Consecutive patients referred for SLOCA underwent comprehensive clinical evaluation and laboratory investigations, brain MRI, DaTscan and a 1-year follow-up. Results: Among 80 patients, 26 had MSA-C, 22 another diagnosis, and 32 no diagnosis at the end of the follow-up. At baseline, MCP hyperintensity and HCB were more frequent in patients finally diagnosed with MSA-C than in other patients with SLOCA (p < 0.0001), and had the highest specificity (98.5%) and positive predictive value (91.7%) for the diagnosis of MSA-C, compared to all other MRI signs. The most relevant MRI sequence regarding HCB sign was the T2-proton density (DP) weighted. All MRI features were more frequent with disease duration. No correlation was found between any MRI feature and neither clinical data, nor dopaminergic neuronal loss (p = 0.5008), except between vermis atrophy and UPDRSIII score. Conclusion: MCP hyperintensity and HCB sign should be added into the list of additional features of possible MSA-C. MRI signal abnormalities suggestive of MSA-C should be searched for in suitable sequence. [ABSTRACT FROM AUTHOR]