REM sleep behavior disorder in early Parkinson’s disease predicts the rapid dopaminergic denervation

ObjectiveTo test the hypothesis that REM sleep behavior disorder (RBD) in early Parkinson's disease (PD) predicts rapid progression of dopaminergic denervation.Methods123I-FP-CIT single photon emission computed tomography (SPECT) scans were performed sequentially at baseline, 1 year, 2 years, and 4 years in 416 de novo patients with PD. RBD screening questionnaire scores >5 at baseline placed the participant in the likely-RBD group. Temporal changes in the specific binding ratio (SBR; caudate, putamen. sum of both, striatum) were compared between the likely-RBD and the non-likely-RBD groups for more or less affected striatum with a repeated measure ANOVA.ResultsLikely-RBD was reported in 37.7% of the drug-naïve PD patients at baseline. The likely-RBD and non-likely-RBD groups did not have significant differences in the baseline clinical features including gender, age, disease duration, UPDRS motor score, and striatal SBR. Striatal SBR decreased significantly over four years in both groups (P < .001). In the analysis of a more affected striatum, striatal SBR decreased significantly faster in the likely-RBD group than in the non-likely-RBD group (P < .05 for all), whereas it was not statistically significant for the less affected striatum. The mean striatal SBR value (mean value of both striata), especially the caudate SBR, indicated greater acceleration of denervation in the likely-RBD group than in the non-likely-RBD group over time (P < .05).ConclusionLikely-RBD in PD predicts accelerating dopaminergic denervation, thereby implicating it as a marker for a poor prognosis or distinctive subtype in PD.     

Decreased single-photon emission computed tomographic {123I}β-CIT striatal uptake correlates with symptom severity in parkinson's disease

Previous studies have utilized single-photon emission computed tomography (SPECT) to demonstrate decreased {¹²³I}β-CIT striatal uptake in idiopathic Parkinson disease (PD) patients. The present study extendss this work by examining SPECT outcome measures in a larger group of PD patients with varying disease severity. Twenty-eight l-dopa-responsive PD patients (Hoehn-Yahr stages 1–4) and 27 healthy controls had SPECT scans at 18 to 24 hours after injection of {¹²³I}β-CIT. Specific to nondisplaceable striatal uptake ratios (designated V_3″) were correlated with Hoehn-Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS) subscores. Linear discriminant function analyses utilizing striatal uptakes, putamen-to-caudate ratios, and ipsilateral-contralateral asymmetry indices were performed. Decreased striatal tracer uptake (V_3″) was correlated with total UPDRS score for both contralateral and ipsilateral striatum. Putamen uptake was relatively more reduced than caudate with mean putamen:caudate ratios of 0.50 ± 0.17 and 0.82 ± 0.09 for PD patients and controls, respectively. Ipsilateral:contralateral asymmetry was significantly greater in PD patients than controls. Discriminant function analysis utilizing V_3″ for ipsilateral and contralateral caudate and putamen correctly classified all 55 cases. These data demonstrate Marchked differences in {¹²³I}β-CIT SPECT measures in healthy controls and PD patients. The significant correlation of SPECT measures with motor severity suggests {¹²³I}β-CIT may be a useful Marchker of disease severity in PD.     

SPECT imaging of pre- and postsynaptic dopaminergic alterations in L-dopa-untreated PD

BACKGROUND: In PD, presynaptic dopamine transporters are known to be decreased, whereas postsynaptic striatal D2 receptors are proposed to be upregulated. However, the relationship between these alterations is not clear. OBJECTIVE: To evaluate the ability of SPECT to detect both the pre- and postsynaptic dopaminergic alterations of the striatum in patients with L-dopa-untreated PD. METHODS: We studied 10 L-dopa-untreated patients with clinically mild PD and 21 age-matched normal controls. Individuals had both presynaptic [123I]beta-CIT dopamine transporter and postsynaptic [123I]IBF D2 SPECT studies 1 week apart. RESULTS: In PD patients, the dopamine transporter binding potential Rv ipsilateral/contralateral to the most affected limbs was 30%/41%, 41%/50%, and 59%/68% lower than controls for caudate, anterior putamen, and posterior putamen, respectively. These bilateral Rv decreases showed a lateralized difference more reduced in the contralateral striatum as well as intrastriatal differences most reduced in the posterior putamen. In contrast, in PD patients the D2 binding potential Rv ipsilateral/contralateral was 15%/16% higher for caudate, 18%/14% higher for anterior putamen, and 28%/31% higher for posterior putamen. These bilateral Rv increases showed no lateralized differences and less marked intrastriatal differences. The motor Unified Parkinson's Disease Rating Scale scores negatively correlated with dopamine transporter Rv but not with D2 Rv. CONCLUSIONS: SPECT imaging can detect characteristic dopaminergic alterations in the striatum of dopa-untreated PD patients including the upregulation of postsynaptic D2 receptors (denervation supersensitivity). SPECT is widely available and is a promising clinical tool to evaluate PD patients.     

Anxiety is associated with striatal dopamine transporter availability in newly diagnosed untreated Parkinson's disease patients

BackgroundAnxiety is a common non-motor symptom among patients with Parkinson's disease (PD). Although the etiology of anxiety in PD is likely to be multifactorial, a dysfunction in the dopaminergic system might be implicated in its pathogenesis. The aim of our study was to investigate a possible dopaminergic mechanism involved in anxiety in newly diagnosed never-medicated PD patients using SPECT and ¹²³I-FP-CIT as the dopamine transporter ligand.MethodsThirty-four newly diagnosed, untreated PD patients with asymmetric motor symptoms were included in the study: 17 patients with right- and 17 with left-motor onset, matched for age, disease duration and motor disability constituted the group. They were all evaluated for anxiety and depression and underwent an SPECT with ¹²³I-FP-CIT. Dopamine transporter (DAT) availability values for right and left caudate and putamen were calculated and compared between patients with and without anxiety. Regression analyses were also performed in order to correlate DAT availability with the severity of the anxiety symptoms.ResultsComparison between PD patients with and those without anxiety revealed significant differences of DAT availability in all the examined regions except the right putamen. In the group of patients considered as a whole, a significant correlation was found between increased anxiety severity and decreased DAT availability in right caudate.ConclusionsWe reported an association between nigrostriatal DAT availability deficits and anxiety symptoms in newly diagnosed, untreated PD patients. Our results suggest that hypofunction of the nigrostriatal dopaminergic system may represent one of the functional anomalies involved in anxiety in PD from the earliest stages of disease and irrespective of any therapy.     

Visual assessment of dopaminergic degeneration pattern in <Superscript>123</Superscript>I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease

The aim of this study was to investigate whether visual assessment of ¹²³I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (¹²³I-FP-CIT) single photon emission computed tomography (SPECT) in addition to quantitative analyses can help to differentiate idiopathic Parkinson's disease (PD) from atypical parkinsonian syndromes (APS). From a consecutive series of patients examined with ¹²³I-FP-CIT SPECT (n = 190) over a three-year period we identified 165 patients with a clinical diagnosis of PD (n = 120) or APS (n = 45). ¹²³I-FP-CIT SPECT results were analysed visually and quantitatively and compared for PD and APS and for the subgroup of patients with early PD and APS (disease duration <5 years). According to predefined visual patterns of dopaminergic degeneration the results were graded as normal (grade 5) or abnormal (grade 1–4), distinguishing a posterior-anterior degeneration pattern (“egg shape”) from a global and severe degeneration pattern (“burst striatum”). Visual assessment of ¹²³I-FP-CIT SPECT showed significant different dopaminergic degeneration patterns for PD and APS patients. A grade 1 (“burst striatum”) degeneration pattern was predominantly associated with APS patients. In contrast to that, a grade 2 (egg shape) degeneration pattern was the characteristic finding in PD patients. In a subgroup of patients with early disease, visual assessment with identification of the burst striatum degeneration pattern provided 90% positive predictive value and 99% specificity for the diagnosis of APS. Quantitative analysis of striatal binding ratios failed to depict these different degeneration patterns in PD and APS patients. Visual assessment of the pattern of dopaminergic loss in ¹²³I-FP-CIT SPECT shows different patterns of dopaminergic degeneration for PD and APS patients. Therefore, it could provide valuable information to distinguish APS from PD patients, especially in early stages of disease. Within the first 5 years of disease, the occurrence of a burst striatum degeneration pattern has a high positive predictive value of APS.     

123I-MIBG cardiac uptake,smell identification and 123I-FP-CIT SPECT in the differential diagnosis between vascular parkinsonism and Parkinson's disease

Vascular parkinsonism (VP) may occur as a distinct clinicopathological entity but the comorbid presence of vascular damage in Parkinson's disease (PD) is very frequent too. This differential diagnosis has therapeutic and prognostic implications but remains challenging as the usefulness of a number of supporting tools is still controversial.ObjectiveTo ascertain the clinical value of cardiac ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) SPECT, olfactory function and ¹²³I-FP-CIT SPECT as supporting tools in the differential diagnosis between VP and PD.MethodsCross-sectional study of 15 consecutive patients with suspected VP, 15 PD patients and 9 healthy subjects. Cardiac ¹²³I-MIBG SPECT (heart-to-mediastinum ratio) and olfactory testing (University of Pennsylvania Smell Identification Test-UPSIT) were performed in all of them. ¹²³I-FP-CIT SPECT was performed in VP-suspected patients.ResultsHeart-to-mediatinum ratio was significant lower in suspected VP (mean 1.45) and PD (mean 1.16) compared to control group (mean 1.69) (p = 0.017 and p < 0.0001). VP patients presented a higher ratio than PD patients (p = 0.001). Control group presented a significant higher UPSIT score (mean 30.71) when compared to both VP (mean 18.33) and PD (mean 15.29) (p = 0.001 for both groups). Those VP with a cardiac ¹²³I-MIBG non suggestive of PD were more likely to have a higher UPSIT score (p = 0.006). ¹²³I-FP-CIT SPECT imaging was heterogeneous (7/15 VP normal, 3/15 abnormal suggestive of PD and 5/15 abnormal but atypical for PD).ConclusionsThe use of cardiac ¹²³I-MIBG SPECT and to a lesser extent UPSIT could assist the differential diagnosis between VP and PD in subjects in which the diagnosis remains uncertain despite ¹²³I-FP-CIT SPECT imaging.     

Extrastriatal 123I-FP-CIT SPECT impairment in degenerative parkinsonisms

IntroductionNeuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a case-controlled region-of-interest (ROI)-based analysis of ¹²³I–N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (¹²³I-FP-CIT) images to measure extrastriatal regional deficits in PD and APS, and assess their added diagnostic value in discriminating degenerative parkinsonisms from other conditions.MethodsWe included 157 patients with early degenerative parkinsonism (mean age 72.6 years, 44% female, mean disease duration at scan 1.6 years), i.e. PD (n = 59), multiple system atrophy parkinsonian variant (MSA-P, n = 17), progressive supranuclear palsy (PSP, n = 28), corticobasal syndrome (CBS, n = 19), dementia with Lewy bodies (DLB, n = 34) as well as 58 similarly-aged control participants. ¹²³I-FP-CIT SPECT images were processed with statistical parametric mapping 12 (SPM12)-based PETPVE12 software and subjected to partial volume effect correction for ROI-based group comparisons.ResultsRelative to controls, all forms of degenerative parkinsonism showed decreased ¹²³I-FP-CIT uptake in caudate nucleus, putamen but also pallidum and insula. In addition, a significant uptake reduction was observed in thalamus for MSA-P and PSP, in midbrain for PD and PSP, and in the amygdala for PSP (ANCOVA controlling for age, sex and antidepressant medication, all Bonferroni-corrected p < 0.007). Receiver-operating characteristics area-under-the-curve showed that adding extrastriatal evaluation led to higher accuracies in separating degenerative conditions from control participants (96.1% vs 94.9% with striatal ROIs only, p = 0.045).ConclusionThis study provides evidence of a major extrastriatal ¹²³I-FP-CIT impairment, and therefore of an altered serotonergic transmission in PD and APS, confirming previous neuropathological and SERT imaging findings.     

Correlation of Parkinson's disease severity and duration with 123I-FP-CIT SPECT striatal uptake.

The variability in clinical features and the masking effects of drug therapy in Parkinson's disease (PD) can affect clinical assessment of disease severity. The aim of this study was to assess the imaging of dopamine transporters using 123I-FP-CIT SPECT and its correlation with disease staging, severity, and duration. Differences between the clinical severity of the onset and non-onset side and the corresponding striatal uptake ratios were also examined. Forty-one patients with PD (nine unilateral, 32 bilateral clinical features) were studied. Clinical severity was determined by using the Unified Parkinson's Disease Rating Score (UPDRS). Unilateral UPDRS was calculated from unilateral arm and leg resting and action tremor, rigidity, finger taps, hand movements, alternating movements, and leg agility. 123I-FP-CIT striatal uptake was expressed as the ratio of specific:nonspecific (SP:NS) uptake for defined brain areas. Patients with PD who had unilateral symptoms showed a significant difference between the ipsilateral and contralateral SP:NS ratios in both the caudate and putamen, but there was a considerable overlap between between the two sides. This result was repeated in patients with bilateral symptoms and there was overlap of SP:NS ratios between the two groups. For the whole group of patients with PD, striatum, caudate, and putamen SP:NS ratios correlated with disease severity assessed by UPDRS and duration of disease. The SP:NS ratios correlated with the bradykinesia subscore but not with rigidity or tremor subscore. In conclusion, this study provides further evidence that the SP:NS ratio is a robust measure of disease severity correlating with duration of PD. However, variability in uptake values suggest that factors other than nigrostriatal degeneration may contribute to disease severity. Correlation with bradykinesia but not with tremor may indicate an origin for tremor outwith the dopamine transporter system. 123I-FP-CIT SPECT offers significant potential in defining the nigrostriatal changes in PD.     

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug‐naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross‐sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single‐photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [¹²³I]FP‐CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age‐moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. © 2014 International Parkinson and Movement Disorder Society     

[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

OBJECTIVES: The main neuropathological feature in Parkinson's disease is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine (DA) transporters in the striatum. [123I]beta-CIT single photon emission computed tomography (SPECT) studies have demonstrated this loss of striatal DA transporter content in Parkinson's disease in vivo. However, studies with this radioligand also showed that an adequate imaging of the striatal DA transporter content could only be performed on the day after the injection of radioligand, which is not convenient for outpatient evaluations. Recently, a new radioligand [123I]FP-CIT, with faster kinetics than beta-CIT, became available for imaging of the DA transporter with SPECT, and the applicability of this ligand was tested in patients with early and advanced Parkinson's disease, using a one day protocol. METHODS: [123I]FP-CIT SPECT was performed in six patients with early and 12 patients with advanced Parkinson's disease, and in six age matched healthy volunteers. RESULTS: Compared with an age matched control group striatal [123I]FP-CIT uptake in patients with Parkinson's disease was decreased, and this result was measurable three hours after injection of the radioligand. In the Parkinson's disease group the uptake in the putamen was reduced more than in the caudate nucleus. The contralateral striatal uptake of [123I]FP-CIT was significantly lower than the ipsilateral striatal uptake in the Parkinson's disease group. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. A subgroup of patients with early Parkinson's disease also showed significantly lower uptake in the putamen and lower putamen:caudate ratios than controls. CONCLUSION: [123I]FP-CIT SPECT allows a significant discrimination between patients with Parkinson's disease and age matched controls with a one day protocol, which will be to great advantage in outpatient evaluations.     

Seven tesla MRI of the substantia nigra in patients with rapid eye movement sleep behavior disorder

IntroductionSusceptibility-weighted imaging of the substantia nigra (SN) both at 7 and 3 Tesla (T) has shown high accuracy in distinguishing patients with Parkinson's disease (PD) and healthy subjects (HS). Patients with rapid eye movement (REM) behavior disorder (RBD) can develop synucleinopathies, and such risk is higher with dopamine transporter single photon emission tomography (123I-FP-CIT SPECT) evidence of nigro-striatal dysfunction. We aimed at evaluating SN 7T magnetic resonance imaging (7T-MRI) in patients with RBD and determining the agreement between MRI and 123I-FP-CIT SPECT.MethodsFifteen patients with idiopathic RBD confirmed by polysomnography and a recent 123I-FP-CIT SPECT underwent a 7T MR by using three-dimensional gradient-recalled-echo multiecho susceptibility-weighted imaging of the SN; the findings were randomly presented with those of 14 HS and 28 patients with PD and blindly evaluated by an expert neuroradiologist, according to recently published criteria. MRI and SPECT results were also compared.ResultsNine subjects with RBD had abnormal SPECT; among them, the findings of 7T-MRI were rated abnormal in eight. Out of six subjects with RBD with normal SPECT, the 7T-MRI findings of five were rated normal. The Cohen's kappa statistic value of agreement was 0.722.ConclusionGradient-recalled-echo multiecho susceptibility-weighted imaging of the SN at 7T is abnormal in 60% of patients with RBD. The 7T-MRI and 123I-FP-CIT SPECT results showed good agreement. 7T-MRI of the SN could represent a safe marker for neurodegenerative disease in patients with RBD, however longitudinal study is warranted.     

Imaging of dopamine transporters with [123I]FP-CIT SPECT does not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson's disease

Parkinson's disease (PD) is characterized neuropathologically by degeneration of the nigrostriatal dopaminergic pathway. With natural aging there is loss of dopaminergic cells in the substantia nigra and, consequently, loss of dopamine transporters in the striatum. It has been suggested that PD is caused by an accelerated rate of cell death. Conceptually, symptoms in idiopathic PD become apparent after a critical level of cell loss, the "symptom threshold." It has been suggested that this symptom threshold is independent of age. In this study, [123I]FP-CIT SPECT was used to assess the effect of aging on the density of striatal dopamine transporters in vivo in controls (n = 36) and early, drug-naive, patients with PD (n = 32). We found a significant age-associated decline of [123I]FP-CIT binding to striatal dopamine transporters in controls, but not in parkinsonian patients. This finding might give further support for the existence of an age-independent threshold in PD. In a subgroup of patients with hemi-PD, we found a significant loss of dopamine transporters bilaterally in the caudate nucleus and putamen. This loss was more pronounced in the putamen than in the caudate nucleus and the contralateral binding was significantly lower than the ipsilateral binding. By using age-corrected data, we estimated that in our particular patient group motor signs started when the loss of [123I]FP-CIT binding ratios in the putamen was 46-64%.     

Residual striatal dopaminergic nerve terminals in very long‐standing Parkinson's disease: A single photon emission computed tomography imaging study

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long‐standing PD has not yet been specifically explored. Therefore, we performed [¹²³I]‐FP‐CIT single photon emission computed tomography (SPECT) in 15 patients with very long‐standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [¹²³I]‐FP‐CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD. © 2010 Movement Disorder Society     

Hyperdopaminergism in lenticulostriate stroke-related restless legs syndrome: an imaging study

ObjectiveThe pathophysiology of restless legs syndrome (RLS) involves a dopaminergic dysregulation that remains poorly understood, with controversial data from the literature. Stroke-related RLS is a rare condition that involves primarily the basal ganglia, the paramedian pons, and the thalamus. Given these elements, we studied dopaminergic metabolism in patients with RLS secondary to lenticulostriate infarction using structural and nuclear imaging in the striatum ipsilateral to the infarction area, as compared to the contralateral side. We hypothesized that dopaminergic metabolism would be impaired in the striatum ipsilateral to stroke.MethodsIn this observational case-control study, we aimed to prospectively include patients with RLS secondary to lenticulo-striate infarction, for analyses of dopamine dysfunction ipsilateral to stroke as compared to the contralateral striatum and to a control population. Four patients fulfilled inclusion criteria with either de novo RLS or major exacerbation of RLS existing prior to stroke, and all four patients were included. Structural imaging was performed using brain magnetic resonance imaging, and the stroke-induced metabolic modifications were assessed by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET). Dopamine reuptake via DAT was explored using ¹²³I-FP-CIT SPECT. PET with ¹⁸F-FDOPA was used to evaluate the functional integrity of the presynaptic dopaminergic synthesis.ResultsThe only structure damaged in all patients was the body of the caudate nucleus, right-sided for three and left-sided for one, as illustrated by magnetic resonance imaging. ¹⁸F-FDG PET showed a hypometabolism in the infarcted area, the ipsilateral thalamus, and the contralateral cerebellum. All patients displayed, in the ipsilateral putamen, increased dopaminergic tone.ConclusionThe present findings suggest that increased dopaminergic tone in the striatum may participate in the pathogenesis of RLS. These observations should encourage further research on RLS symptomatic with well-defined lesions as a promising way to further improve our understanding of its pathophysiology.     

BDNF levels and nigrostriatal degeneration in “drug naïve” Parkinson's disease patients. An “in vivo” study using I-123-FP-CIT SPECT

IntroductionParkinson's Disease (PD) is a common neurodegenerative disorder, characterized by a progressive loss of dopaminergic neurons and whose cause remains unclear. Brain-Derived Neurotrophic factor (BDNF) is a protein involved in dopaminergic cells survival. Previous studies have shown decreased serum BDNF levels in PD patients.Aim and objectivesThe aim of the study was to evaluate serum BDNF levels in a group of recently diagnosed non-medicated PD patients and its relationship with the nigrostriatal system degeneration using I-123-FP-CIT.Methods30 recently diagnosed, unmedicated PD patients were included in this study. Serum BDNF levels were measured twice using a sandwich enzyme linked immunoabsorbent assay and compared with levels of 27 unrelated Caucasian healthy adults.A I-123-FP-CIT SPECT was performed in all PD Patients in order to assess the association between serum BDNF levels and I-123-FP CIT uptake in several brain areas using a volumetric semi-automatic method.ResultsPD patients showed lower serum BDNF levels (Median = 49.61, IQ range: 43.55 to 61.82) than the controls (Median = 68.82, IQ range: 51.87 to 88.14) (U = 211.00, z = -3.10, p = 0.002). BDNF levels in PD patients correlated with both caudate (Spearman r = 0.58, p = 0.001 for ispilateral and r 0.55, p = 0.002 for contralateral) and putamen (Spearman r = 0.68, p < 0.001 for ipsilateral and r = 0.80, p < 0.001 for contralateral) I-123-FP-CIT uptake ratios.ConclusionsSerum BDNF levels were lower in recently diagnosed, untreated PD patients compared to controls. These lower levels were significantly correlated with the I-123-FP-CIT uptake ratios.     

SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson's disease with urinary dysfunction.

We studied a correlation of urinary dysfunction with nigrostriatal dopaminergic deficit in Parkinson's disease (PD) by single-photon emission computed tomography (SPECT) imaging of dopamine transporter with [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT). Eleven patients were enrolled in the study, including four men and seven women, with a mean age of 64 years. Seven patients had urinary symptoms 1-5 years after the onset of motor disorder, which included nighttime frequency in six, urinary retardation in four, daytime frequency in one and urge urinary incontinence in one. Using a SPECT camera, the ratio specific to nondisplaceable [123I]-beta-CIT uptake, designated as "striatal V3" was obtained in the caudate, anterior and posterior putamen 24 h after the tracer injection. The striatal V3 was compared in patients with and without urinary dysfunction, and between men and women, using unpaired Student's t-test. Correlation of motor dysfunction and duration of illness with urinary dysfunction, was also analyzed. In the patients, there was a reduction of [123I]-beta-CIT binding in the striatum on both sides, particularly in the putamen contralateral to the affected body side. The striatal V3 of the caudate (p<0.01, Rt; p<0.05, Lt), anterior putamen (p<0.05, Rt) and posterior putamen (p<0.05, Rt) in patients with urinary dysfunction was significantly reduced than those without urinary dysfunction. No sex difference was seen in reduction of [123I]-beta-CIT binding. Urinary dysfunction in PD was more common in patients with higher Unified Parkinson's Disease Rating Scale (UPDRS) score, higher Hoehn-Yahr grade, but not in those with longer duration of disease, although there was no statistical significance. It is likely that our results reflect the association of urinary dysfunction and degeneration of the nigrostriatal dopaminergic cells in PD.     

123I]beta-CIT SPECT imaging assessment of the rate of Parkinson's disease progression.

BACKGROUND: [123I]beta-CIT and SPECT imaging of the dopamine transporter is a sensitive biomarker of PD onset and severity. OBJECTIVE: In this study, the authors examine the change in [123I]beta-CIT uptake in sequential SPECT scans to assess the rate of progression of the dopaminergic terminal loss in patients with PD. METHODS: Patients with PD (n = 32) and healthy controls (n = 24) recruited from the Yale Movement Disorders Center underwent repeat [123I]beta-CIT SPECT imaging during a 1- to 4-year period. The primary imaging outcome was the ratio of specific to nondisplaceable striatal activity. Disease severity was assessed by Hoehn and Yahr staging, and Unified Parkinson Disease Rating Scale after 12 hours off drug. RESULTS: Sequential SPECT scans in PD subjects demonstrated a decline in [123I]beta-CIT striatal uptake of approximately 11.2%/year from the baseline scan, compared with 0.8%/year in the healthy controls (p < 0.001). Although [123I]beta-CIT striatal uptake in the PD subjects was correlated with clinical severity, the annual percentage loss of [123I]beta-CIT striatal uptake did not correlate with the annual loss in measures of clinical function. CONCLUSIONS:- The rate of dopaminergic loss in PD is significantly greater than that of healthy controls, and [123I]beta-CIT SPECT imaging provides a quantitative biomarker for the progressive nigrostriatal dopaminergic degeneration in PD. As new protective and restorative therapies for PD are developed, dopamine transporter imaging offers the potential to provide an objective endpoint for these therapeutic trials.     

Assessing dopaminergic function in Parkinson’s disease: levodopa kinetic-dynamic modeling and SPECT

Abstract. Levodopa pharmacokinetic-phamacodynamic (PK-PD) modeling may be able to test the functional integrity of the nigrostriatal dopaminergic system in Parkinsons disease (PD). [¹²³I]-FP-CIT SPECT imaging of striatal dopamine transporters has also been introduced for the evaluation of presynaptic dopaminergic homeostasis. We aimed to assess the intrapatient relation between levodopa PK-PD and SPECT measures of dopaminergic function in PD. Thirty-five PD patients, 1 to 4 on the Hoehn and Yahr (H&Y) scale, enrolled in the study. Each patient was examined by levodopa PK-PD modeling and SPECT imaging. Primary measure outcomes were the levodopa half-life in the effect compartment (t1/2_eq) for PKPD modeling and the ratio of specific to non specific (SP/NSP) tracer striatal uptake for SPECT. Levodopa t1/2_eq was highly significantly correlated with H&Y scale (r = –0.815, p < 0.0001), Unified Parkinsons disease Rating Scale (UPDRS) (r = –0.691, p < 0.0001) and PD symptom duration (r = –0.647, p < 0.0001). SPECT contralateral putamen SP/NSP ratio showed the most significant correlations with clinical indicators of disease severity: H&Y, r = –0.526, p < 0.002; UPDRS, r = –0.523, p < 0.002; symptom duration, r = –0.513, p < 0.002. Significant correlations were observed between levodopa t1/2_eq and putamen SP/NSP ratios, yielding the closest correlation for the contralateral region (r = 0.522, p < 0.002). An indirect PK-PD dopaminergic functional variable and direct SPECT measures of presynaptic dopaminergic system homeostasis were in close agreement with clinical data and correlated to each other. Levodopa PK-PD modeling can be a practical clinical tool indirectly assessing the functional integrity of the nigrostriatal dopaminergic system in PD patients.     

Association between dopaminergic dysfunction and anxiety in de novo Parkinson's disease

ObjectivesTo explore the relationships between nigrostriatal dysfunction and neuropsychiatric symptoms (including anxiety, depression and apathy) in a large cohort of newly diagnosed, drug-naïve Parkinson disease (PD) patients compared to a cohort of healthy controls (HC).MethodsThis is a cross-sectional analysis of the Parkinson's Progression Markers Initiative (PPMI) cohort at baseline, including 405 PD patients and 187 HC. Nigrostriatal degeneration was evaluated by means of SPECT DAT scan. Relationships between neuropsychiatric symptoms and DAT uptakes were analysed by means of stepwise multiple regression analysis.ResultsIn the PD group, lower DAT uptake in the right caudate was associated with higher STAI trait subscore (β = −2.939, 95%CI: −4.634 to −1.254, p = 0.001). Depression and apathy scores were not related with DAT uptakes. No associations were found in the HC group.ConclusionsOur cross-sectional analysis of the PPMI data shows that lower caudate DAT uptake is associated with higher level of anxiety. The data strengthens the relationship between dopaminergic dysfunction and neuropsychiatric symptoms in early PD.     

Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP.

It is often difficult to differentiate clinically between Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP).The objective of this work was to investigate whether combined pre‐ and postsynaptic dopaminergic single photon emission computed tomography (SPECT) scanning can reliably demonstrate changes in the nigrostriatal dopaminergic system and help differentiate between normal controls, PD, MSA, and PSP patients. We performed SPECT evaluation of the dopamine transporter (DAT) and dopamine D2 receptors (D2). SPECT scans using [¹²³I]β‐CIT (for DAT) and [¹²³I]IBF (for D2) were performed in 18 patients with PD (12 dopa‐naïve and 6 on levodopa and/or dopamine agonists), 7 with MSA of the striatonigral degeneration type, 6 with PSP, and 29 normal controls. Antiparkinsonian drugs were withheld for at least 12 hours before the scans. DAT and D2 binding potentials (Rv = V₃/V₂) were measured for caudate, anterior, and posterior putamen on the sides ipsilateral and contralateral to the worst motor symptoms. DAT binding in the posterior putamen was markedly reduced in all patients. However, D2 binding in posterior putamen was significantly increased in dopa‐untreated PD, being greater than the normal range in 4 of 12 (33%), and it was significantly reduced in MSA, being below the normal range in 5 of 7 (71%). None of the patients with PD showed reduced D2 binding below the normal range in posterior putamen. The degree of DAT binding could not discriminate between the patient groups. The ratio of posterior putamen to caudate percentage D2 Rv compared with the controls showed an opposite pattern between PD or PSP and MSA; the caudate was greater in 16 of 18 with PD and 6 of 6 with PSP, whereas caudate was less in 5 of 7 with MSA. These findings suggest that DAT SPECT may be useful in differentiating parkinsonism from controls and D2 SPECT in further differentiating MSA from Parkinson's disease and possibly PSP. © 2002 Movement Disorder Society.