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.     

Striatal dopamine function in a family with multiple SCA-3 phenotypes

We present single photon emission computed tomography (SPECT) studies using 123IFP-CIT (DAT scan) and 123I-IBZM imaging, performed on four members of a family with genetically proven spinocerebellar ataxia type 3 (SCA-3). DAT scan showed significant asymmetric decreased binding in the striatum in the two members with predominant parkinsonian phenotype, with mild and symmetric decreased binding in the member with the cerebellar phenotype, and normal in the asymptomatic member. The IBZM SPECT studies showed mild and asymmetrical reduction of the striatal dopamine D2 receptor density (parkinsonian members). SCA-3 can present with a levodopa responsive parkinsonism phenotype, and an abnormal DAT scan showing predominant impairment of presynaptic dopamine function.     

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.     

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.     

Impact of subcortical white matter lesions on dopamine transporter SPECT

Subcortical arteriosclerotic encephalopathy (SAE) can affect the nigrostriatal system and presumably cause vascular parkinsonism (VP). However, in patients with SAE, the differentiation of VP from idiopathic Parkinson’s disease (IPS) is challenging. The aim of the present study was to examine the striatal dopamine transporter (DAT) density in patients with parkinsonism and SAE. Fifteen consecutive patients with parkinsonian symptoms displayed SAE, as detected by magnetic resonance imaging (MRI). Fifteen retrospectively chosen, matched patients with diagnosis of IPS without any abnormalities in MRI served as a reference group. DAT SPECT was performed using the tracer ¹²³I-FP-CIT. Scans were acquired on a triple-head SPECT system (Multispect 3, Siemens) and analysed using the investigator-independent BRASS? software (HERMES). In the SAE group, a DAT deficit was observed in 9/15 patients. In contrast, all patients from the IPS group showed a reduced DAT binding (p = 0.008). The specific binding ratios (BR) of putamen contralateral to the side of the more affected limb versus occipital lobe were in trend higher in patients with SAE versus patients in the IPS-group (p = 0.053). Indices for putaminal asymmetry (p = 0.036) and asymmetry caudate-to-putamen (p = 0.026) as well as the ratio caudate-to-putamen (p = 0.048) were significantly higher in IPS patients having no SAE. DAT deficit was less pronounced in patients with SAE and parkinsonism than in patients with IPS without any abnormalities in the MRI. A potential role of DAT SPECT in the differential diagnosis of VP and IPS requires more assessments within prospective studies.     

Dopamine transporter SPECT: How to remove subjectivity?

Clinical criteria enable accurate and reliable diagnosis of parkinsonian syndromes when cardinal clinical features are fully developed. Single photon emission computed tomography (SPECT) investigating the striatal dopamine transporter (DAT) status have been suggested to increase the diagnostic accuracy in uncertain parkinsonian syndromes such as isolated tremor symptoms not fulfilling essential tremor criteria, as well as drug‐induced, vascular and psychogenetic parkinsonism. Several approaches for the analysis of the striatal DAT distribution have been tested for their ability to analyze and quantify SPECT images. Visual assessment of DAT binding and semiquantitative analysis using region of interests have been recommended by Nuclear Medicine Associations to be incorporated in the routine work‐up of DAT‐SPECT. Besides these observer dependent approaches, fully automated image‐analysis techniques have been validated in the clinical setting. Their potential as tools to improve the diagnostic accuracy in patients presenting with parkinsonian features is reviewed here. © 2009 Movement Disorder Society     

The relationship between cerebral vascular disease and parkinsonism: The VADO study

BackgroundThe observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined.MethodsWe recorded clinical features, chronic response to levodopa and vascular risk factors in a cross-sectional cohort of consecutive elderly patients with possible Parkinson's disease (PD) or VP recruited in 20 centers in Italy.ResultsWe included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake.ConclusionsMultiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likely.     

FMR1 gene expansion and scans without evidence of dopaminergic deficits in parkinsonism patients

PurposeTo determine if patients with parkinsonism and fragile X mental retardation 1 (FMR1) gene expansions have a striatal dopamine deficit similar to Parkinson disease (PD) patients.ScopeThe authors studied three patients with parkinsonism carrying small expansions in the FMR1 gene (41–60 CGG) with [¹²³I]β-CIT SPECT imaging. The patients responded to dopaminergic medications, but had preserved dopamine transporter density.ConclusionsThese results suggest that parkinsonism associated with smaller FMR1 expansions may be related to mechanisms other than pre-synaptic dopaminergic changes and may represent a potential explanation for at least some parkinsonian cases with scans without evidence of dopaminergic deficits (SWEDD).     

Dopamine transporter density measured by [123I]β-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia

The clinical distinction between dopa-responsive dystonia (DRD) and juvenile Parkinson's disease (JPD) can pose a diagnostic challenge. Both conditions are dopa responsive. However, long-term L-dopa benefit is very different between the two. The difference in the prognosis is due to presence or absence of nigral cell loss. In JPD, there is degenerative nigral cell loss, wherease there are enzymatic defects in dopamine synthesis without cell loss in DRD. Mutations have been found in the GTP cyclohydrolase I (GCH-I) and tyrosine hydroxylase genes in DRD. As the discovered mutations are multiple and more are expected to be found, it is difficult to confirm or exclude DRD by mutation studies. Measurement of cerebrospinal fluid (CSF) neopterin will detect DRD from mutations in the GCH-I gene but not from mutations in tyrosine hydroxylase. The dopamine transporter (DAT) is a protein in the dopaminergic nerve terminals. (1R)-2β-Carbomethoxy-3β-(4-[¹²³I]iodophenyl)tropane ([¹²³I]β-CIT) is a ligand for the DAT, and it was shown to be a useful nuclear imaging marker for neurons that degenerate in Parkinson's disease (PD). As DRD was shown to have a normal DAT without nigral cell loss in a postmortem study, we predicted that the DAT measured in vivo by nuclear imaging will be normal in DRD and will differentiate DRD from JPD. Therefore, we performed [¹²³I]β-CIT single-photon emission computed tomography ([¹²³I]β-CIT SPECT) in clinically diagnosed DRD, PD, and JPD, and examined whether DAT imaging can differentiate DRD from PD and JPD. We then examined whether DAT imaging can provide a screening tool for molecular genetic studies, by studying mutations in the candidate gene GCH-I and measuring CSF neopterin. Five females (4 from two families, and 1 sporadic) were diagnosed as DRD based on early-onset foot dystonia and progressive parkinsonism beginnig at ages 7 to 12. All patients were functioning normally on L-dopa 100 to 250 mg/day for up to 8 years. SPECT imaging was obtained after intravenous injection of [¹²³I]β-CIT; 15 healthy volunteers served as normal control, and 6 PD and 1 JPD as disease controls. [¹²³I]β-CIT striatal binding was normal in DRD, whereas it was markedly decreased in PD and JPD. Gene analysis showed a novel nonsense mutation in the GCH-I gene in one family. No mutation was found in the other family or in the sporadic case. CSF neopterin was markedly decreased in the 4 tested patients. [¹²³I]β-CIT SPECT is a sensitive method for probing the integrity of nitegrity of nigrostriatal dopaminergic nerve terminals. A normal striatal DAT in a parkinsonian patient is evidence for a nondegenerative cause of parkinsonism and differentiates DRD from JPD. Finding a new mutation in one family and failure to demonstrate mutations in the putative gene in other cases supports the usefulness of DAT imaging in diagnosing DRD.     

Clinical and [<Superscript>123</Superscript>I]FP-CIT SPET imaging follow-up in patients with drug-induced parkinsonism

We recently found that patients with drug-induced parkinsonism (DIP) may have normal (group I) or abnormal (group II) putamen [¹²³I]FP-CIT DAT (dopamine transporter) binding. In this study we reassessed clinical features and DAT binding in 19 of the original 32 patients (10 of group I and 9 of group II) after a 19–39-month follow-up period and tested the effects of chronic levodopa treatment in both cohorts of patients. In group I patients, [¹²³I]FP-CIT SPET (single photon emission tomography) was still normal in all patients at follow-up; DAT binding and UPDRS (Unified Parkinson’s Disease Rating Scale) motor score values did not differ from baseline. In group II patients, [¹²³I]FP-CIT SPET was still abnormal at follow-up; putamen DAT binding was significantly reduced and UPDRS III score higher compared to baseline. Levodopa treatment improved motor symptoms in three out of ten patients of group I and in eight out of nine patients of group II. No adverse psychiatric effects were observed in any of the patients. This study shows that DAT binding imaging may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals in the context of a progressive degenerative parkinsonism. Patients with DIP may benefit from levodopa therapy, particularly when dopamine nerve terminal defects are present, and this should be considered in the therapeutic management of these patients.     

123I-MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis

ObjectivesDifferential diagnosis of Parkinson’s disease (PD) and other neurodegenerative parkinsonism by clinical consensus criteria and diagnostic imaging is often difficult. ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) myocardial scintigraphy is a useful imaging tool for differentiating PD from other parkinsonism. The purpose of the present study is to systematically review and perform a meta-analysis of studies on the diagnostic performance of ¹²³I-MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism, specifically multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration.MethodsA computer literature search of the PubMED/MEDLINE database was conducted to find relevant published articles on ¹²³I-MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism. We used the bivariate random-effects model to obtain the pooled estimates of the sensitivity and specificity and the corresponding 95% confidence intervals.ResultsThirteen studies comprising 845 patients including 625 PD and 220 other neurodegenerative parkinsonism were analyzed. The pooled sensitivity and specificity to differentiate PD from other neurodegenerative parkinsonism by the early heart-to-mediastinum (H/M) ratio were 82.6% and 89.2%, respectively, and those by the delayed H/M ratio were 89.7% and 82.6%, respectively. When PD was limited to early stage (Hoehn-Yahr stage 1 or 2), the pooled sensitivity and specificity by the delayed H/M ratio were 94.1% and 80.2%, respectively.ConclusionsThe present meta-analysis confirmed high sensitivity and specificity of ¹²³I-MIBG myocardial scintigraphy for differentiating PD from other neurodegenerative parkinsonism in both early and delayed imaging phases. Furthermore, ¹²³I-MIBG myocardial scintigraphy was highly effective for distinguishing early PD.     

Impact of dopamine transporter single photon emission computed tomography imaging using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes

To assess the impact of I-123 ioflupane single photon emission computed tomography (SPECT) imaging on classifying patients with striatal dopaminergic deficits. Sixty-one patients with an initial diagnosis of parkinsonism or uncertain tremor disorder were screened and followed-up for one year. All patients were re-examined by two neurologists at our centre and were classified as having neurodegenerative or non-neurodegenerative disorders. Patients underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and classified as normal or abnormal (indicative of neurodegenerative disorders). The overall agreement of the SPECT imaging results with the initial classification was 65.6% (kappa = 0.229, p = 0.074) but was 90.2% (kappa = 0.782, p < 0.001) with the classification of the neurologists at our centre. I-123 ioflupane SPECT imaging is a valuable method in the evaluation of patients presenting clinically with uncertain parkinsonian syndromes or for whom diagnostic doubt exists.     

Metabolic activity of the subthalamic nucleus in a primate model of L-Dopa-unresponsive parkinsonism

Abstract

Increased activity of the subthalamic nucleus (STN) is critical in mediating motor symptoms of Parkinson's disease. To determine if altered STN activity also occurs in levodopa (L-Dopa)-unresponsive parkinsonism due to a combined nigral and striatal degeneration, metabolic activity of the STN was assessed using cytochrome oxidase (CO) histochemistry in monkeys with nigral, striatal, or nigral+striatal degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and/or 3-nitropropionic acid (3NP). MPTP- and MPTP+3NP-treated monkeys had a similar parkinsonian score and were clinically indistinguishable. However, CO activity in the STN was significantly increased in MPTP-induced parkinsonism but not in MPTP+3NP-induced striatonigral degeneration. These results indicate that metabolic activity of the STN is normal following a combined nigral+striatal degeneration and may help to understand the lack of effect of STN stimulation in L-Dopa-unresponsive parkinsonism.     

Diabetes is associated with postural instability and gait difficulty in Parkinson disease

BackgroundComorbid diabetes may be associated with more severe motor impairment in Parkinson disease. In normal elderly individuals, diabetes is associated with parkinsonian features, including gait difficulty and rigidity, though not tremor. Whether diabetes contributes to increased motor dysfunction in Parkinson disease by exacerbating nigrostriatal dopaminergic denervation or through intensification of extranigral pathology is unknown.MethodsWe performed a case–control study (n = 39) involving 13 Parkinson disease subjects (age 66.4yrs ± 5.5; duration of disease 6.9yrs ± 4.4) with diabetes and 26 age, gender, and duration-of-disease-matched Parkinson disease controls without diabetes. All subjects underwent [¹¹C]dihydrotetrabenazine vesicular monoamine transporter type-2 positron emission tomography imaging to assess striatal dihydrotetrabenazine distribution volume ratio and Unified Parkinson disease rating scale motor examination to determine rigidity, bradykinesia, tremor, and postural instability and gait difficulty subscores. Magnetic resonance imaging scans were analyzed to assess leukoaraiosis burden.ResultsAfter controlling for nigrostriatal dopaminergic denervation, Parkinson disease subjects with diabetes displayed greater postural instability and gait difficulty subscores (t = 3.81, p = 0.0005). There were no differences in bradykinesia, rigidity, or tremor subscores between cases and controls. The association between diabetes and postural instability and gait difficulty persisted after controlling for comorbid hypertension and body mass index. Leukoaraiosis, distal vibratory sense, and levodopa dose equivalents did not differ significantly between cases and controls.ConclusionsDiabetes may contribute to postural instability and gait difficulty in Parkinson disease through mechanisms other than nigrostriatal dopaminergic denervation.     

Valproic acid-induced parkinsonism: Levodopa responsiveness with dyskinesia

BackgroundValproic acid is a drug used for the treatment of a variety of psychiatric and neurological disorders. While it is well known to cause postural tremor, hyperammonemia, slowness, and sedation, it has also been described to occasionally cause a reversible form of parkinsonism.Materials and methodsA series of five cases is reported.ResultsAll patients were taking the drug for at least several months before onset of their parkinsonian symptoms. Parkinsonism was defined by the presence of bradykinesia, rigidity, postural instability, and resting tremor, but not postural or action tremor. After discontinuing their valproic acid, improvement was seen by all patients. The course of improvement took days to months after discontinuance. Two of these patients responded to dopaminergic therapy, with drug-induced dyskinesia observed in one. In another patient, valproic acid was thought to unmask underlying Parkinson's Disease; this patient benefited from levodopa as well.ConclusionValproic acid-induced parkinsonism can look identical to idiopathic parkinsonism. In all five cases, the relationship between the valproic acid use and parkinsonism was initially unclear because of the delayed and insidious onset. Our finding of levodopa responsiveness and dyskinesia added to the diagnostic confusion. This treatment responsiveness also set it apart from neuroleptic-induced parkinsonism. In all cases improvement of symptoms occurred after discontinuation of the offending medication.     

Evidence of delayed nigrostriatal dysfunction in corticobasal syndrome: A SPECT follow-up study

ObjectiveTo demonstrate that degeneration of substantia nigra neurons may occur at later stages of disease in some patients with corticobasal syndrome (CBS) who evidenced preserved nigrostriatal pathway at a baseline FP-CIT SPECT study.BackgroundCurrent pathological criteria for the definite diagnosis of corticobasal degeneration consider substantia nigra cell loss as a mandatory finding. However, dopamine transporter SPECT imaging performed in a large cohort of CBS patients showed about 10% of normal scans.MethodsWe describe 4 patients with clinical diagnosis of CBS and normal FP-CIT SPECT at baseline whose tracer uptake resulted pathological at 1-year follow-up scan. Clinical assessment has been performed at the time of SPECT scan. A semi-quantitative approach was performed for striatal FP-CIT binding values.ResultsBaseline SPECT scans have been performed after 2.3 ± 1.5 years from onset. All CBS patients presented asymmetric rigid-akinetic parkinsonism (mean Hoehn-Yahr stage 2.5; UPDRS motor score 18) with poor levodopa response and ideo-motor limb apraxia. At follow-up, neurological examination revealed some additional features, including limb dystonia, language impairment, postural instability, ocular gaze impairment, alien limb. All patients showed pathological FP-CIT uptake at the SPECT performed 10–15 months apart from the baseline scan.ConclusionsOur longitudinal FP-CIT SPECT findings support in vivo the hypothesis that substantia nigra neuronal loss may occur at later stages in some patients with CBS, despite early extrapyramidal symptoms.     

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.     

Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT

Ten healthy subjects and 16 patients with early Parkinson’s disease (PD) were examined with single photon emission computed tomography (SPECT) and [¹²³I]β-CIT, a ligand for the dopamine (DA) transporter. Only drug-naive patients were examined since the expression of and binding to DA transporters may be influenced by dopaminergic medication. The main finding was a significant reduction in [¹²³I]β-CIT binding in the ipsi- and contralateral striatal regions, especially in the putamen, which showed a mean reduction of 65% of the control mean. Discriminant function analysis of the putaminal [¹²³I]β-CIT binding measures classified 100% of the cases in the correct group. Disease severity correlated negatively and highly significantly with the binding measures. Tremor ratings did not correlate with the SPECT measures, whereas rigidity, and to a lesser extent bradykinesia, did. Patients with unilateral PD showed a bilateral loss of striatal DA transporters. Our findings indicate that with [¹²³I]β-CIT SPECT it is possible to diagnose PD in subjects with very mild symptoms and signs. Moreover, finding a bilateral loss of striatal DA transporters in patients with unilateral PD also suggests that it may be possible to identify subjects in the preclinical phase of the disease. Received: 12 February 1997 Received in revised form: 12 September 1997 Accepted: 16 September 1997     

123I‐Ioflupane SPECT in the diagnosis of suspected psychogenic Parkinsonism

Psychogenic Parkinsonism (PsyP) can be clinically difficult to differentiate from Parkinson's disease (PD). Striatal dopamine transporter (DAT) imaging could be helpful in differentiating them. We performed ¹²³I‐Ioflupane single‐photon emission computed tomography (SPECT) in 9 patients with suspected PsyP. In 1 patient, ¹²³I‐Ioflupane SPECT disclosed bilateral decrease of striatal tracer uptake that indicated nigrostriatal degeneration. In this patient, a parkin gene mutation was detected. In the other 8 patients, ¹²³I‐Ioflupane SPECT was normal and supported the initial suspicion of PsyP. Normal DAT imaging supports the diagnosis of PsyP, whereas reduced striatal tracer uptake suggests an underlying neurodegenerative Parkinsonism and should encourage the search for additional causes for the syndrome. © 2006 Movement Disorder Society     

Are dopa-responsive dystonia and Parkinson’s disease related disorders? A case report

Objectivel-Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by an excellent response to low dosages of levodopa. DRD patients may also develop Parkinsonism which resembles idiopathic Parkinson’s disease. In classical DRD no changes in the dopaminergic uptake have been observed.MethodsA 65-year old woman presented with clinically remarkably slowly progressing Parkinson’s disease (PD) without any dystonic signs and excellent response to dopaminergic medications. We obtained a [¹²³I] FP-CIT-SPECT (DaTSCAN?) in order to elucidate a striatal dopaminergic deficit.ResultsWe found a reduced uptake in the [¹²³I] FP-CIT-SPECT (DaTSCAN?) contralateral to the more affected body side. Additionally, the patient showed a heterozygous deletion of the GHC1 gene.ConclusionsPatients with mild parkinsonian symptoms, excellent response to low dosages of dopaminergic drugs and a reduced dopamine-transporter uptake in [¹²³I] FP-CIT-SPECT might more commonly be GCH1 mutation carriers than has previously been supposed. PD patients with a positive family history of DRD and combination of these clinical symptoms should be offered genetic counselling and testing for GCH1.