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.     

The pattern of FP-CIT PET in pure white matter hyperintensities–related vascular parkinsonism

ObjectivesTo determine whether vascular parkinsonism (VaP) patients with visually normal dopamine transporter (DAT) scans have presynaptic dopaminergic depletion.MethodsWe enrolled 23 VaP patients who had parkinsonism, relevant diffuse subcortical white matter hyperintensities (WMH), and visually normal DAT scans, 23 Parkinson's disease (PD) patients, and 31 control subjects. By quantitatively analyzing ¹⁸F–N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) positron emission tomography, we compared the pattern of striatal DAT availability among groups. The discriminatory power of striatal DAT availability to differentiate VaP patients from control subjects or PD patients was assessed using receiver operating characteristics (ROC) analyses. Additionally, correlation analysis was performed to determine whether WMH severity or Unified Parkinson Disease Rating Scale Part III (UPDRS-III) score is related to presynaptic dopaminergic depletion in VaP.ResultsVaP patients exhibited decreased DAT availability in all striatal subregions, including posterior putamen, compared to control subjects. VaP patients and control subjects had similar patterns of anteroposterior and ventrodorsal DAT gradients in caudate and putamen level, but VaP patients exhibited significantly different patterns at putamen level, relative to PD patients. The severity of periventricular WMH was significantly correlated with all substriatal DAT availability in VaP, but not with UPDRS-III scores. The ROC analysis showed that DAT availability in caudate and posterior putamen had a fair discriminatory power when differentiating VaP patients from control subjects.ConclusionsThis study demonstrates that VaP patients with WMH exhibited diffusely decreased DAT availability without any specific regional gradients of DAT patterns distinct from either control subjects or PD patients.     

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     

DaTSCAN (123I-FP-CIT SPECT) imaging in early versus mid and late onset Parkinson's disease: Longitudinal data from the PPMI study

IntroductionIt has been reported that early onset Parkinson's Disease (PD) patients have a less profound dopaminergic degeneration. The aim of the current study was to determine whether there are longitudinal differences in dopaminergic denervation [signal reduction in 123I-FP-CIT SPECT] in early versus mid and late onset PD.MethodsDaTSCAN (123I-FP-CIT SPECT) imaging was acquired at Parkinson's Progression Markers Initiative (PPMI) imaging centers and sent to the imaging core for calculation of striatal binding ratios. Data from the PPMI database of 58 early de novo PD patients (age ≤ 50 years) were compared to those of 362 mid and late onset PD patients (age > 50 years).ResultsAlthough raw striatal binding ratios were higher in early onset versus mid/late onset PD, especially on the ipsilateral side, such differences were not observed, and were in fact reversed in the contralateral putamen, after age correction. The rate of signal decline was similar between the two groups. Interestingly, based on both raw and age-adjusted data, caudate nucleus and putamen asymmetry (contralateral/ipsilateral ratio) was more pronounced in early onset PD. Striatal asymmetry also significantly correlated with age at onset as a continuous variable.ConclusionEarly onset PD patients exhibited similar rates of decline of dopaminergic denervation compared to mid/late onset PD. These results are not supportive of a more benign disease in this subgroup. The more pronounced asymmetry in early onset PD may however signify a qualitatively different pattern of neurodegeneration compared to mid/late onset PD.     

Minimal parkinsonism in the elderly is associated with striatal dopamine loss and pontine structural damage

IntroductionTo investigate whether neurodegeneration underlying Parkinson's disease (PD) accounts for a substantial proportion of cases of minimal parkinsonism in the elderly.MethodsWe recruited 48 consecutive subjects with minimal parkinsonism who visited the clinic with cognitive complaints. All subjects did not show findings compatible with PD on ¹⁸F-FP-CIT PET scans, and had no evidence of other neurodegenerative disorders. Striatal dopamine transporter (DAT) availability was quantified, and mean diffusivity (MD) values in the pons were calculated to characterize structural damage using diffusion tensor imaging. Additionally, 35 patients with PD and 21 healthy controls were included as reference groups.ResultsIndividuals with minimal parkinsonism (mean age, 73.23 ± 7.03 years) exhibited mild decrease in DAT availability in the posterior putamen, which was at a level between that of healthy controls and patients with PD. DAT availability in the caudate and anterior putamen was also mildly decreased in the minimal parkinsonism group. Individuals with minimal parkinsonism also tended to have higher MD values in the pons compared to healthy controls.ConclusionsOur results suggest that a substantial proportion of minimal parkinsonism is associated with nigrostriatal dopamine depletion and pontine structural damage, which may be related to the disease process of prodromal PD.     

Striatal [123I]β-CIT SPECT and prefrontal cognitive functions in Parkinson's disease

Summary. Twenty non-demented patients with idiopathic Parkinson's disease (PD) underwent single photon emission computed tomography (SPECT) with [¹²³I]β-CIT to further investigate the contribution of nigrostriatal dysfunction to cognitive and motor deficits. Compared to matched controls PD patients showed normal verbal intelligence, short-term memory and phasic alertness. There were significant (p < 0.05) deficits in tests of verbal working memory (digit ordering, reading span), strategic memory (story recall) and executive functions (card sorting), indicating a "prefrontal" cognitive deficit. Significant (p < 0.05) correlations were observed between dopamine transporter (DAT) density in the putamen and motor deficits as well as between DAT density in both striatal compartments (head of the caudate nucleus and putamen) and prefrontal functioning. Age was a major contributing factor to both cognitive status and nigrostriatal integrity as measured by [¹²³I]β-CIT SPECT. These results support the view that the striatum is part of a neuronal network that is mediating prefrontal cognitive functions. Received February 26, 1999; accepted August 18, 1999     

Dopaminergic degeneration and perfusional impairment in Lewy body dementia and Alzheimer’s disease

Abstract. The clinical differentiation of Lewy body dementia (LBD) from Alzheimers disease (AD) may be difficult. The aim of the present study was to assess the dopamine transporter function and the perfusional pattern in LBD and AD in vivo. Twenty patients with probable LBD and 24 with probable AD underwent on 2 separate days a brain perfusional SPECT with 99mTc-ECD and a SPECT with ¹²³I-FP-CIT, a ligand of dopamine transporter. In LBD a significantly (p<0.0005) lower ratio of specific (bilateral caudate nucleus, putamen) to non-specific (occipital cortex) ¹²³I-FP-CIT binding than in AD was reported. Perfusional data (SPM analysis) showed a significant (p<0.001) decrease of temporo-parietal blood flow in AD versus LBD, whereas in LBD a significant (p<0.001) occipital hypoperfusion with respect to AD was reported. Our findings confirm that dopaminergic nigrostriatal function is impaired in LBD. The selective occipital hypoperfusion in LBD needs to be further investigated.     

Dopamine transporter binding in chronic manganese intoxication

Abstract. Chronic exposure to manganese may induce parkinsonism similar to idiopathic Parkinsons disease (PD). However, clinical manifestations of manganism also have some features different from PD. The mechanisms of manganese-induced parkinsonism remain not fully understood. ^99mTc-TRODAT-1 is a cocaine analogue that can bind to the dopamine transporter (DAT) site reflecting the function of presynaptic dopaminergic terminals. The purpose of this study was to evaluate DAT function using ^99mTc-TRODAT-1 to investigate the integrity of the presynaptic dopaminergic terminals in manganese-induced parkinsonism. Brain ^99mTc-TRODAT-1 single photon emission computed tomography was performed in 4 patients with chronic manganese intoxication in a ferromanganese smelting plant in Taiwan. Twelve PD patients and 12 healthy volunteers served as abnormal and normal controls, respectively. Clinically, all manganism patients had a bradykinetic-rigid syndrome. The scores of the Unified Parkinsons Disease Rating Scale ranged between 19 and 64. The uptake values of the ^99mTc-TRODAT-1 were 0.868±0.136 in the right corpus striatum and 0.865±0.118 in the left, as compared with 0.951±0.059 and 0.956±0.058, respectively for the normal controls. The data were significantly higher than 0.250±0.070 and 0.317±0.066 respectively for the PD patients. Interestingly, there was a mild decrease in the uptake of ^99mTc-TRODAT-1 in the putamen and the ratio of putamen and caudate when compared with the normal controls. Although the DAT shows a slight decrease in the putamen of manganism patients as compared with that of the normal controls, the data indicate that the presynaptic dopaminergic terminals are not the main target of chronic manganese intoxication. In addition ^99mTc-TRODAT-1 SPECT can provide a useful, convenient and inexpensive tool for differentiation between chronic manganism and PD.     

123I]-FP/CIT SPECT imaging for distinguishing drug-induced parkinsonism from Parkinson's disease.

Parkinsonism in patients taking neuroleptic medications might be induced by dopamine receptor blockade alone or by dopamine blockade with nigrostriatal dysfunction. The differentiation between Parkinson's disease (PD) and drug-induced parkinsonism (DIP) is difficult to assess on clinical grounds alone. In this study, we have evaluated the clinical characteristics and striatal binding of (123)I-FP-CIT (N-omega-fluoropropyl-2beta-carboxymethoxy-3beta-{4-iodophenyl}tropane) in patients who developed DIP. A total of 20 patients (mean age, 62 +/- 13 years) who developed parkinsonism while on neuroleptic agents and 10 age-matched controls were enrolled. [123]-FP-CIT single-photon emission computed tomography (SPECT) was performed in all subjects. Neurological assessment was performed with the Motor part of the Unified Parkinson's Disease Rating Scale. [123]-FP-CIT binding of the entire striatum, caudate, and putamen was calculated. Patients were divided into two subgroups according to SPECT results for comparison of clinical characteristics. There were 9 patients who had normal scans and 11 who showed significantly diminished striatal binding, suggesting degeneration of the nigrostriatal system. Subanalyses of abnormal scans revealed significantly diminished binding in the caudate (P < 0.001 for right and left caudate) and putamen (P = 0.002 and P < 0.05 for right and left putamen, respectively). There were no differences in clinical features between patients with normal and abnormal scans. Symptoms included asymmetric tremor, bradykinesia, and rigidity in both groups. Freezing gait was present in two patients with normal scans. These results indicate that DIP is clinically indistinguishable from PD. Brain imaging with FP-CIT helps to determine whether DIP is entirely drug-induced or an exacerbation of subclinical PD.     

Serotonergic neurotransmission in early Parkinson's disease: A pilot study to assess implications for depression in this disorder

Abstract

Objectives. Depression, a disease usually accompanied by a serotonergic deficit, has been observed in about 40% of patients suffering from Parkinson's disease (PD). Thus, a serotonergic dysfunction in PD can be assumed. We aimed to investigate the interaction between serotonergic (5-HT) and dopaminergic activity in early PD. We hypothesized a serotonergic as well as a dopaminergic deficit in PD patients. We also assumed a correlation between these neurotransmitters indicating a relationship between dopaminergic and serotonergic function in PD. Methods. Nine unmedicated PD patients before and 12 weeks after l-dopa treatment and nine healthy subjects were examined using the loudness dependence of auditory evoked potentials (LDAEP), a promising indicator of central serotonergic function. Dopaminergic transporters (DAT) were collected using ¹²³I-FP-CIT and single photon emission computer tomography (SPECT). LDAEP values were correlated with ¹²³I-FP-CIT SPECT data. Results. A significant difference between LDAEP of controls and patients (P= 0.05) suggested lower serotonergic activity in PD. Twelve weeks after initiation of l-dopa treatment this difference was lost between patients and controls (P= 0.20). There was a trend towards a correlation between LDAEP and DAT (r= 0.65; P = 0.057) of the unmedicated patients, suggesting a low serotonergic activity may be related to a dopamine deficit in PD. Conclusions. Our results support the hypothesis that serotonergic neurotransmission is decreased in untreated PD and suggest that a low serotonergic activity may be related to the dopamine pathology in PD. This could be related to the high prevalence of depression in PD.     

Substantia nigra echogenicity is correlated with nigrostriatal impairment in Machado-Joseph disease

BackgroundSeveral studies have demonstrated increased substantia nigra (SN) echogenicity in Parkinson's disease (PD) and Machado-Joseph disease (MJD). Pathological substrate of PD is characterized by dopaminergic nigrostriatal cell loss, also found in MJD. Also, SN hyperechogenicity might be associated with nigrostriatal dysfunction in PD, when comparing dopamine transporter binding with SN echogenicity. The present study aimed to correlate the SN echogenic size and striatal dopamine transporter density in MJD patients.MethodsWe performed TCS in 30 subjects and SPECT with [^99mTc]-TRODAT-1 in 18 subjects with MJD. Fifteen healthy subjects matched for age and gender formed a control group. TCS and [^99mTc]-TRODAT-1 SPECT findings from both MJD patients and control subjects were compared.ResultsThere were no differences regarding age (p = 0.358) or gender (p = 0.566) between groups (MJD versus control group). Mean DAT binding potentials and SN echogenicity were significantly different between groups. There was a significant negative correlation with regard to the SN echogenic size and the ipsilateral striatal TRODAT-1 uptake: the higher the SN echogenicity, the lower the DAT uptake in the ipsilateral cerebral hemisphere.ConclusionIncrease in SN echogenic size likely correlates with presynaptic dopaminergic nigrostriatal dysfunction in MJD, suggesting a concurrent in vivo pathophysiological mechanism.     

The interaction between dopamine transporter function,gender differences,and possible laterality in depression

The Dopamine Transporter (DAT) can reflect the general state of striatal dopamine activity. This current study examined the role of DAT in depressed patients before and after bupropion treatment. Twenty-three patients with major depression were treated with bupropion for 8 weeks. Before and after the treatment, they and 20 normal subjects received the radioligand ^99mTc-TRODAT-1 single photon emission tomography scan (SPECT). Subjects were assessed with the Hamilton Depression Rating Scale. All DAT images were spatially normalized to an averaged brain template, and the specific binding ratios of the striatum, caudate, and putamen were calculated according the formulae of: [region counts] / [occipital counts] - 1. Depressed patients had greater DAT availability on both sides of the striatum. DAT binding was significantly decreased in the striatum after bupropion treatment. Women had higher initial and final DAT binding in the right and left caudate when compared to depressed men. DAT binding decreased in all areas of the brain in women after successful antidepressant treatment, but only in the right caudate of men. Depressed patients had a greater availability of DAT; it was decreased after bupropion treatment.Women seemed to have more DAT availability.     

Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease

We studied whether the ¹²³I‐FP‐CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 ± 12.7 years) underwent the ¹²³I‐FP‐CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and ¹²³I‐FP‐CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with ¹²³I‐FP‐CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia. © 2008 Movement Disorder Society     

The role of <Superscript>123</Superscript>I-FP-CIT-SPECT in the differential diagnosis of Parkinson and tremor syndromes: a critical assessment of 125 cases

¹²³I-FP-CIT-SPECT is useful in the differential diagnosis of Parkinson’s disease (PD) and tremor syndromes. Recently, there have been reports on normal nigrostriatal uptake of radio ligands in PD patients, referred to as scans without evidence of dopaminergic deficit (SWEDDs). Furthermore, a dopaminergic deficit has been described in some cases of different tremor types. We sought to clarify the occurrence of SWEDDs in PD and a possible association of various tremor types with PD. We performed a retrospective case analysis of 125 patients with diagnostically uncertain Parkinsonian or non-Parkinsonian tremor syndromes with clinical assessments and ¹²³I-FP-CIT-SPECT. A total of 36/40 (90%) patients with the predominant clinical feature of a postural and/or kinetic tremor showed normal DAT SPECT; 73/85 (86%) with predominant clinical symptoms of PD showed abnormal DAT SPECT with lower overall radio ligand uptake and a significant asymmetry contralateral to the clinically more affected side. In all, 4/40 (10%) of non-Parkinsonian tremor patients had abnormal DAT SPECT, but no corresponding asymmetry of radio ligand uptake. Probable essential tremor was considered clinically in follow-up assessments although final diagnosis of these four tremor cases remains inconclusive. A total of 12/85 (14%) clinically suspected PD patients had normal DAT SPECT (SWEDDs). Clinical reassessment identified two patients with dystonic tremor. Five patients with a positive response to levodopa remained unclear. In four cases of suspected PD with normal DAT SPECT, non-neurologic diseases were identified. One case showed a complete and spontaneous remission of symptoms. DAT SPECT offers an objective method to confirm or exclude a dopaminergic deficit in tremor predominant parkinsonism for clinically inconclusive cases. There was no evidence of a decrease in DAT binding in the majority of patients with postural and/or kinetic tremor. The striatal asymmetry index is a further helpful tool for differentiating PD from non-PD tremor syndromes.     

123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy

Abstract. We used SPECT and the tracer ¹²³I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinsons disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51±0.39, p<0.01) compared with MSA-P (0.70±0.33) and PD (0.95±0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83±0.12, p<0.01) than in PD (0.51±0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.     

Effect of dopaminergic medication on adenosine 2A receptor availability in patients with Parkinson's disease

ObjectiveTo assess the necessity of withdrawing dopaminergic medication in Parkinson's disease (PD) patients for accurate estimation of adenosine 2A receptor (A_2AR) availability using [¹¹C]TMSX PET imaging. This was accomplished by studying the short-term effect of the cessation of dopaminergic medication on A_2AR availability in non-dyskinetic patients with PD treated with dopaminergic medication.MethodsEight PD patients (age 67.9 ± 5.6 years; 6 men, 2 women) without dyskinesia were enrolled in this study. A_2AR availability was measured using PET imaging with a [7-methyl-¹¹C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([¹¹C]TMSX) radioligand after a short term cessation of dopaminergic medication (12hrs for levodopa, 24hrs for dopamine agonists and MAO-B inhibitors). Repeated PET imaging was performed while the patients were back ‘on’ their regular dopaminergic medication (median 13 days after first imaging). Conventional MRI was acquired for anatomical reference. Specific binding of [¹¹C]TMSX was quantified as distribution volume ratios (DVR) for caudate, pallidum and putamen using Logan graphical method with clustered gray matter reference region.ResultsNo significant differences were observed for the DVRs in all three striatal regions between ‘on’ and ‘off’ medication states. Strong correlations were also observed between the two states. Statistical equivalence was found in pallidum (TOST equivalence test, p = 0.045) and putamen (TOST equivalence test, p = 0.022), but not in caudate DVR (TOST equivalence test, p = 0.201) between the two medication states.ConclusionsOur results show that dopaminergic medication has no significant short-term effect on the availability of A_2A receptors in putamen and pallidum of patients with PD. However, relatively poor repeatability was demonstrated in the caudate.     

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.     

Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C)

Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent (¹²³I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([¹²³I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [¹²³I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [¹²³I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.     

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.