Atypical Parkinsonian Syndromes Patients Research Articles

Evoked potential response in patients with idiopathic Parkinson’s disease and atypical parkinsonian syndromes: A comparative study

Patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonian syndromes (APSs) suffer from a range of disorders, especially in balance and locomotion, which necessitate visual, auditory, and somatosensory inputs. In this study, IPD patients, APS patients, and healthy controls (HCs) (n = 50 per group) underwent a series of assessments for visual evoked potentials (VEP), brainstem auditory evoked response (BAER), and short-latency somatosensory evoked potentials (SSEP). Results showed that VEP P100 latency was prolonged in multiple system atrophy-cerebellar type (MSA-C), multiple system atrophy-parkinsonian type (MSA-P), and corticobasal ganglionic degeneration (CBD) patients. The latency of peaks III and V was prolonged in IPD, MSA-C, dementia with Lewy bodies (DLB), and Parkinson’s disease dementia (PDD). BAER I-III and I-V interpeak latency were prolonged in IPD, DLB, and PDD, whereas BAER I-III, III-V, and I-V interpeak latencies were increased and the V/I amplitude ratio was decreased in MSA-C. The central sensory conduction time (N20-N13) was increased in MSA-P and MSA-C in SSEP. IPD patients had prolonged VEP P100 latency (P < 0.001), lower VEP N75-P100 amplitude (P < 0.001), prolonged BAER I, II, II, IV, V peak latencies (P < 0.001), I-III, I-V interpeak latencies (P < 0.001), lower BAER V/I amplitude ratio (P < 0.001), and prolonged SSEP N13, N20, central sensory conduction time (N20-N13) (P < 0.001) than HCs. IPD patients also had prolonged BAER I, II, II, IV, V peak latencies (P < 0.001), prolonged I-III, I-V interpeak latencies (P < 0.001), and shorter SSEP N13, N20, central sensory conduction time (N20-N13) (P < 0.001) than APS patients. Moreover, APS patients had prolonged VEP P100 and N145 latencies (P < 0.001) and decreased N75-N145 amplitude (P < 0.001) compared to HCs. APS patients also had prolonged BAER II, II, IV, V peak latencies (P < 0.001), prolonged I-III, III-V, I-V interpeak latencies (P < 0.001), decreased V/I amplitude ratio, and prolonged SSEP N13, N20, central sensory conduction time (N20-N13) (P < 0.001) than HCs. Postural instability and gait disorder (PIGD) IPD had significantly prolonged BAER III, V peak latencies (P < 0.05), and prolonged III-V interpeak latencies (P < 0.05) compared to tremor-dominant IPD. Overall, the IPD and APS patients had significant VEP, BAER, and SSEP abnormalities of demyelination and axonal variety in the visual, auditory, and somatosensory pathways. The changes were also correlated with the disease duration and severity. Although the diseases are predominantly motor disorders with significant non-motor components, these electrophysiological abnormalities might open a new avenue to assess the non-motor symptoms.

Predictors of Survival in Atypical Parkinsonian Syndromes in a Tunisian Cohort (P8-11.006)

<h3>Objective:</h3> Our aim was to investigate demographic, clinical and genetic survival factors in a Tunisian cohort with atypical parkinsonian syndromes (APS). <h3>Background:</h3> APS encompass a spectrum of neurodegenerative diseases including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS), all characterized by faster progression and earlier mortality compared to Parkinson’s disease. However, the predictors of survival are still controversial. <h3>Design/Methods:</h3> We conducted a retrospective study over a period of 19 years (2003–2021) in the Department of Neurology of Razi University Hospital, in Tunis, Tunisia, including patients diagnosed with APS. Survival was explored using Kaplan-Meier analysis. Demographic, clinical, neuropsychological features and frequency of Apolipoprotein Epsilon 4 (ApoEɛ4) allele were analyzed in the survival analysis. <h3>Results:</h3> We included 340 APS patients (151 DLB, 74 PSP, 70 MSA, 45 CBS). Median survival was 6 years from disease onset in DLB and MSA and 7 years in PSP and CBS. It was significantly shorter for men (p=0.005) and for patients with memory symptoms at onset (p=0.040) in DLB, later age of onset (&gt;65 years, p=0.021), earlier dysphagia and ApoEɛ4 allele carrying status in PSP patients. In MSA, median survival was shorter in parkinsonian subtype (MSA-P) compared to cerebellar subtype (MSA-C) in patients having urinary dysfunction. Although the presence of stridor was associated with shorter survival (6 vs 9 years), the difference was not statistically significant (p=0.090). In CBS, the presence of alien limb syndrome (p=0.031), dementia (p=0.026) and tremor-dominant parkinsonian syndrome (p=0.019) were associated with shorter survival. <h3>Conclusions:</h3> Our results showed shorter survival in synucleinopathies compared to tauopathies with different predictive demographic and clinical factors across APS. ApoEɛ4 seemed to have an effect only in PSP. Larger prospective studies are needed to better investigate the various survival determinants. <b>Disclosure:</b> Dr. Nasri has nothing to disclose. Ikram Sghaier has nothing to disclose. Mrabet Saloua has nothing to disclose. Mr. Abida has nothing to disclose. Alya GHARBI has nothing to disclose. Amira Souissi has nothing to disclose. Mouna BenDjebara has nothing to disclose. Amina Gargouri has nothing to disclose. Dr. Kacem has nothing to disclose. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Gouider has received research support from Clinical Investigation Center. The institution of Dr. Gouider has received research support from Menactrims.

Role of Apolipoprotein E in the Clinical Profile of Atypical Parkinsonian Syndromes.

Atypical Parkinsonian syndromes (APS) encompass a spectrum of neurodegenerative diseases including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). The effects of the Apolipoprotein E (APOE) gene on APS clinical features are controversial and understudied in several populations. We aimed to explore the influence of APOE genotype on clinical features in an APS Tunisian cohort. We included clinically diagnosed APS patients genotyped for APOE, and analyzed the clinical and APOE genotype associations. A total of 328 APS patients were included, comprising 184 DLB, 58 PSP, 49 MSA, and 37 CBS. Significant differences in initial Mini-Mental State Examination and Frontal Assessment Battery scores according to APOE genotypes (P=0.05 and 0.0048) were found. Executive dysfunction (P=0.026) disorientation (P=0.025), and hallucinations (P<0.001) were more pronounced among APOE-ɛ4 carriers particularly in DLB. Memory disorders were also correlated to APOE-ɛ4 allele (P=0.048) and were more frequent among DLB and PSP carriers. Depression was associated to APOE-ε4 (P=0.042), more markedly in APOE-ε4-CBS and MSA carriers. Our findings suggested a role of APOE-ε4 in defining a more altered cognitive phenotype with variable degrees across subgroups in APS patients, especially in DLB carriers. This effect mainly concerned executive, memory and orientation functions as well as hallucinations.

CSF and Circulating NfL as Biomarkers for the Discrimination of Parkinson Disease From Atypical Parkinsonian Syndromes: Meta-analysis.

To evaluate whether CSF and circulating neurofilament light chain (NfL), a marker of axonal damage, could discriminate Parkinson disease (PD) from atypical parkinsonian syndromes (APSs). MEDLINE and Scopus were systematically searched, and 15 studies were included (1,035 patients with PD and 930 patients with APS). CSF NfL levels were 1.26 SDs higher in the APS group compared to the PD group (g = 1.26 [95% confidence interval 0.99-1.53]), and circulating NfL levels were 1.53 SDs higher in the APS group compared to the PD group (g = 1.53 [95% confidence interval 1.15-1.91]); 4 studies, 307 patients with PD, 197 patients with APS. Pooled areas under the curve were 0.941 (0.916-0.965) and 0.874 (0.802-0.946) for CSF and circulating NfL, corresponding to average sensitivities of 86% (79%-90%) and 91% (86%-95%), and specificity of 88% (82%-92%) and 76% (62%-85%), respectively. These results strongly support the high diagnostic accuracy of both CSF and circulating NfL in differentiating PD from APS, highlighting their usefulness as promising biomarkers.

Atypical parkinsonian syndromes in a North African tertiary referral center.

IntroductionData on epidemiology of atypical parkinsonian syndromes (APS) in North African countries are limited. Our objective was to study the epidemiological features of APS in a Tunisian population.MethodsWe conducted a 17‐year retrospective cross‐sectional descriptive study in the Department of Neurology at Razi University Hospital. We included all patients responding to consensus diagnosis criteria of APS. We recorded demographic and clinical data. Group differences were assessed with a post hoc ANOVA with a Bonferroni error correction.ResultsWe included 464 APS patients. Hospital prevalence of APS among all parkinsonism cases was 20.6%. Mean annual increase of incidence defined as newly diagnosed APS cases per year reached 38.8%/year. APS were divided into 4 etiological subgroups: dementia with Lewy bodies (DLB; 56.7%); progressive supranuclear palsy(PSP; 16.2%); multiple system atrophy (MSA; 14.6%); and finally corticobasal syndrome (CBS; 12.5%). Sex‐ratio was 1.2. This male predominance was found in all subgroups except MSA (p = .013). Mean age at onset was 68.5 years, most belated in DLB (69.7 years; p < .001). Young‐onset parkinsonism (<40 years) was found only in MSA subgroup (p = .031). Parkinsonism was of late onset (>70 years) in 50.7% of patients and was significantly associated with DLB subgroup (p = .013). Inaugural parkinsonism was associated with CBS and MSA (p = .0497), and gait disorders at disease onset were associated with PSP and MSA (p = .0062). Cognitive and mood disorders were more marked in DLB and most preserved in MSA. Consanguinity was more marked in CBS (p = .037), and family history of dementia and psychiatric diseases was more common in DLB. Thirty‐seven families with similar cases of APS were identified.ConclusionsThis is the largest African epidemiological study on APS. In our population, APS were frequent and dominated by DLB. The age of onset of parkinsonism was the most decisive feature for differential diagnosis.

Distinguishing Parkinson's disease from atypical parkinsonian syndromes using PET data and a computer system based on support vector machines and Bayesian networks.

Differentiating between Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) is still a challenge, specially at early stages when the patients show similar symptoms. During last years, several computer systems have been proposed in order to improve the diagnosis of PD, but their accuracy is still limited. In this work we demonstrate a full automatic computer system to assist the diagnosis of PD using 18F-DMFP PET data. First, a few regions of interest are selected by means of a two-sample t-test. The accuracy of the selected regions to separate PD from APS patients is then computed using a support vector machine classifier. The accuracy values are finally used to train a Bayesian network that can be used to predict the class of new unseen data. This methodology was evaluated using a database with 87 neuroimages, achieving accuracy rates over 78%. A fair comparison with other similar approaches is also provided.

The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes.

The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinson's disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand (123)I-FP-CIT (DaTSCAN(®)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75%) had visually predominant dopamine depletion in putamen, while most APS patients (56%) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

Automated Volumes-of-Interest Identification for Classical and Atypical Parkinsonian Syndrome Differentiation Using T2’ MR Imaging

In clinical routine, patients with classical Parkinsonian syndromes (CPS) need to be differentiated from those with atypical Parkinsonian syndromes (APS), particularly with respect to prognosis and treatment decision. To date, this diagnosis is mainly based on clinical criteria, leading to failure rates up to 25%, motivating the development of image-based decision support systems. Magnetic resonance imaging (MRI) and in particular T2´ image sequences have been suggested as a potential marker for differential diagnosis. The aim of this study was to investigate whether automatically identified T2´ volumes-of-interest (VOIs) can be used for an automatic differentiation of CPS and APS patients. 74 MRI datasets were available for this hypothesis generating trial, including image sequences from 24 healthy subjects, 33 CPS and 17 APS patients. First, a problem-specific reference atlas was generated using the healthy control datasets. Next, patients' datasets were registered to the atlas. Voxel-wise t-tests, reflecting significance levels of T2´ value differences between CPS and APS patients, were then applied for calculation of a p-map. Finally, the calculated p-map was thresholded and a connected component analysis was performed for final VOI detection. In parallel, manually defined VOIs were determined in grey and white matter for comparison. Three VOIs in parts of the basal ganglia and the left occipital lobe were automatically identified by the presented method. There was a trend for higher area under the curve on multivariable receiver operating characteristic curves for automatically determined VOIs over manually defined VOIs (0.939 vs. 0.818, p = 0.0572). The diagnostic role of automatically defined VOIs in differentiation of CPS and APS patients based on T2´ image sequences should be further investigated.

Visual assessment of dopaminergic degeneration pattern in 123I-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 (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan ((123)I-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 (123)I-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). (123)I-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 (123)I-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 (123)I-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.

Prevalence of Parkinson’s disease and atypical parkinsonian syndromes in a rural Japanese district

To investigate the prevalence of Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) in a rural Japanese district. Collaboration with the medical institutions, the long-term care insurance system facilities, and the public health office. The crude prevalence rates were 175 per 100,000 (95% CI: 143-206) for PD, 18 (8-28) for progressive supranuclear palsy, 17 (7-26) for multiple system atrophy (MSA), and 9 (2-16) for corticobasal degeneration. The age-adjusted prevalence rates were 109 per 100,000 (88-134), 10 (2-17), 13 (4-21), and 6 (0-12), for each condition. There was a preponderance of women with PD and of men with APS. Nine of the 116 PD patients and 7 of the 29 APS patients were newly diagnosed in this study. There are high prevalence rates for PD and APS and suboptimal recognition of APS. This is the first epidemiological prevalence study of MSA from Japan.

Pre- and postsynaptic dopamine SPECT in the early phase of idiopathic parkinsonism: a population-based study

The aim of this study was to assess the diagnostic contribution of pre- and postsynaptic dopamine SPECT in drug-naïve patients with early idiopathic parkinsonism and to investigate possible differences between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and possible differences in motor subtypes of parkinsonism. A group of 128 newly diagnosed idiopathic parkinsonian patients and 48 healthy controls was studied. Presynaptic baseline SPECT with (123)I-FP-CIT was performed in all patients and in 120 patients also a baseline postsynaptic SPECT with (123)I-IBZM. Clinical diagnoses were reassessed after 12months. Presynaptic uptake in the putamen and caudate was significantly reduced in patients compared to controls. Presynaptic uptake ratios were not different between PD patients and patients with APS, and postsynaptic uptake in APS was not significantly reduced compared to PD or controls. In half of the APS patients both pre- and postsynaptic uptake ratios were reduced on the same side in the striatum. Impaired motor performance was associated with decreased presynaptic uptake in the putamen in PD. The postural instability and gait difficulty (PIGD) subtype of PD had lower presynaptic uptake ratios than patients with tremor-dominated (TD) symptoms. Not only presynaptic putamen uptake ratios, but also caudate ratios were reduced in a majority of the patients in our study. At baseline scan, i.e. in an early stage of the disease, the accuracy of excluding APS in the whole study population was 85% using a combination of pre- and postsynaptic SPECT. Already at baseline, lower presynaptic SPECT ratios were seen in PD with PIGD at onset compared to those with TD subtype.

The predictive value of transcranial duplex sonography for the clinical diagnosis in undiagnosed parkinsonian syndromes: comparison with SPECT scans

BackgroundTranscranial duplex sonography (TCD) of the substantia nigra has emerged as a promising, non-invasive tool to diagnose idiopathic Parkinson's disease (IPD). However, its diagnostic accuracy in patients with undefined parkinsonism remains to be determined.In this study we determined the predictive value of TCD for the clinical diagnosis in undiagnosed parkinsonian syndromes. Additionally we compared the predictive value of TCD with that of presynaptic and postsynaptic single photon emission computer tomography (SPECT) scans.MethodsWe studied 82 patients with an unclassified parkinsonian syndrome. All 82 patients were subjected to a TCD, 59 of them underwent a presynaptic SPECT scans and 32 underwent a postsynaptic SPECT scan.We determined the diagnostic accuracy of TCD and SPECT scans in differentiating:1) IPD patients from patients without nigrostriatal degeneration and 2) IPD patients from patients with atypical parkinsonian syndromes (APS).To compare the diagnostic accuracy of TCD and SPECT scans, we used the clinical diagnosis after follow-up according to generally accepted clinical criteria as the gold standard. This clinical diagnosis was determined by a movement disorder specialist.3) Finally, we ascertained the predictive value of the TCD for the SPECT result.ResultsThe clinical diagnoses after follow-up resulted in 51 cases of IPD, 7 patients with APS and 17 patients without nigrostriatal degeneration. In total 7 patients remained undiagnosed.1) The accuracy of TCD, assessed by sensitivity and specificity, to differentiate IPD patients from patients without nigrostriatal degeneration was 50% and 82% respectively.For the presynaptic SPECT scans sensitivity was 97% and specificity 100%.2) In differentiating IPD patients from APS patients, the sensitivity and specificity of TCD was 50% and 43% respectively. For presynaptic SPECT scans this was 97% and 0%. For the postsynaptic SPECT scans the sensitivity was 75% and the specificity 81%.3) The positive predictive value (PPV) of an abnormal TCD for an abnormal presynaptic SPECT scan was 88%.ConclusionPresynaptic SPECT scanning has a higher predictive value for the clinical diagnosis than TCD. However, since the PPV of an abnormal TCD for parkinsonism with nigrostriatal degeneration is high, TCD might be used as screening tool, before ordering a presynaptic SPECT.

Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson’s disease

Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinson's disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years' duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis. The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [(123)I]beta-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained. In the group of patients with APS, baseline [(123)I]beta-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups. [(123)I]beta-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.

Patterns of abnormal motor cortex excitability in atypical parkinsonian syndromes

Objective: Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal-ganglionic degeneration (CBGD) are all clinically characterized by an akinetic-rigid syndrome together with a variety of additional signs. We hypothesised that these atypical parkinsonian syndromes (APS) will show distinctive patterns in their motor output upon transcranial magnetic stimulation (TMS) due to their different underlying anatomico-functional deficits. Methods: We performed single and paired-pulse TMS and assessed inhibitory and excitatory response parameters from the first dorsal interosseus muscles in 13 patients with MSA, 18 with PSP, 13 with CBGD, 15 patients with Parkinson's disease and 17 healthy subjects. Results: PSP and MSA patients had significantly enlarged response amplitudes at rest, reduced intracortical inhibition (ICI) and prolonged ipsi- and contralateral silent periods, whereas CBGD patients showed significantly increased motor thresholds, smaller response amplitudes at rest, shortened contralateral silent period, reduced transcallosal inhibition and a reduced ICI. In 22% of APS patients ipsilateral motor responses occurred in upper limb muscles irrespective of the underlying disease. Conclusions: Our results indicate that motor cortex disinhibition is predominant in patients with PSP and MSA. In CBGD more severe neuronal cell loss in the motor cortex itself may lead to hypoexcitability of corticospinal and transcallosal pathways.

The dopamine D2 receptor ligand 18F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism

For therapeutic and prognostic reasons it is important to differentiate between idiopathic parkinsonian syndrome (IPS, Parkinson's disease) and atypical parkinsonian syndromes (APS) like multiple system atrophy or progressive supranuclear palsy. Whereas IPS patients usually show a normal or upregulated postsynaptic dopamine D2 receptor profile, APS patients present decreased postsynaptic tracer binding. The aim of this prospective study was to evaluate the D2 receptor antagonist fluorine-18 desmethoxyfallypride (18F-DMFP), a recently developed positron emission tomography (PET) tracer with better clinical availability than carbon-11 raclopride, for the differential diagnosis of IPS versus APS. The study included 16 healthy control subjects and 35 patients with clinically diagnosed parkinsonism (16 IPS patients, 19 APS patients). All patients underwent PET imaging after injection of 180-200 MBq 18F-DMFP. Receiver operating characteristic (ROC) analyses were performed in order to assess the diagnostic performance of 18F-DMFP PET. We found the striatal 18F-DMFP uptake ratio to be significantly (P<0.01) reduced in the APS patients (2.44+/-0.42) compared with the healthy control subjects (3.61+/-0.43) and the IPS patients (3.21+/-0.78), whereas the uptake ratios of the IPS patients and the control subjects did not differ significantly. For the differential diagnosis of APS versus IPS, the ROC analysis of caudate 18F-DMFP binding showed a specificity, sensitivity and accuracy of 100%, 74% and 86%, respectively, as well as positive and negative predictive values of 100% and 76%, respectively. Based on these first clinical results, we consider 18F-DMFP to be an appropriate PET tracer for the differential diagnosis of parkinsonian syndromes, with the advantage of better clinical availability than 11C-labelled D2 radioligands.