Differential Diagnosis Of Parkinsonian Syndromes Research Articles

Clinical utility of (99m Tc)-TRODAT-1 scans to differentiate Parkinsonian syndromes: case studies and commentary.

The differential diagnosis of Parkinsonian syndromes is challenging, especially in the elderly as they often have complex presentations. Nuclear imaging modalities can increase diagnostic accuracy. Single-photon emission tomography (SPECT) using the ligand (99m Tc)-TRODAT-1 is used overseas but is yet to be approved in Australia. Three pilot cases of clinically unclear Parkinsonian syndromes from the Royal North Shore Hospital Aged Care Department who underwent (99m Tc)-TRODAT-1 scans are described. From experience overseas, the (99m Tc)-TRODAT-1 scan has clinical utility in the differential diagnosis of Parkinsonian syndromes. (99m Tc)-TRODAT-1 has a lower cost and greater availability than other ligands. Our initial scan findings are largely consistent with the clinical picture, but low specific binding can affect scan interpretation. (99m Tc)-TRODAT-1 is a potential tool in the differential diagnosis of Parkinsonian syndromes. Further experience regarding its effect on patient outcomes and cost effectiveness is required before routine clinical use can be recommended.

Neuroimaging in Parkinsonian Disorders.

Neuroimaging (NI) in Parkinson's disease (PD) includes functional techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT), and morphological imaging using magnetic resonance imaging (MRI) and transcranial sonography to probe different aspects of the neurobiology of PD. Changes in neurotransmitters in various regions of the brain and their influence on brain networks is the basis for the motor symptoms of PD which are interrogated by NI. The recent Movement Disorders Society Clinical Diagnostic Criteria for PD (MDS-PD) have included the results of a few of these neuroimaging techniques to serve as single supportive criteria or absolute exclusion criteria for the diagnosis of PD. While dopaminergic imaging is useful in the early stages of disease to differentiate the neurodegenerative versus non-degenerative causes of parkinsonism like essential tremors, it has also been used for the differential diagnosis of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD), for inclusion of PD patients into clinical trials and for evaluating response to cell-replacement therapies in PD. Metabolic patterns on F-18 fluorodeoxyglucose positron emission tomography have been used effectively for the classification and differential diagnosis of the parkinsonian syndromes using visual and quantitative approaches. Disease related network-patterns have been used for a completely automated approach to differential diagnosis of parkinsonian syndromes on a single case basis. Structural MRI and advanced MR techniques have been used for the classification of PD and the atypical parkinsonian syndromes. Thus, multimodal imaging in PD may aid in an early, accurate and objective diagnostic classification by highlighting the underlying neurochemical and neuroanatomical changes that underlie this spectrum of disorders. The present challenge in PD is to develop radioligands which could bind selectively to alphasynuclein in-vivo.

Differential diagnosis of parkinsonian syndromes using dopamine transporter and perfusion SPECT

ObjectiveWe aimed to assess whether a combined analysis of dopamine transporter (DAT)- and perfusion-SPECT images (or either) could: (1) distinguish atypical parkinsonian syndromes (APS) from Lewy body diseases (LBD; majority Parkinson disease [PD]), and (2) differentiate among APS subgroups (progressive supranuclear palsy [PSP], corticobasal syndrome [CBS], and multiple system atrophy [MSA]). MethodsWe recruited consecutive patients with neurodegenerative parkinsonian syndromes (LBD, n = 46; APS, n = 33). Individual [123I]FP-CIT- and [123I]iodoamphetamine-SPECT images were coregistered onto anatomical MRI segmented into brain regions. Striatal DAT activity and regional perfusion were extracted from each brain region for each patient and submitted to logistic regression analyses. Stepwise procedures were used to select predictors that should be included in the models to distinguish APS from LBD, and differentiate among the APS subgroups. Receiver-operating characteristic (ROC) analyses were performed to measure diagnostic power. Leave-one-out cross-validation (LOOCV) was performed to evaluate the diagnostic accuracy. ResultsThe model to discriminate APS from LBD showed that the area under the ROC curve (AUC) was 0.923, while the total diagnostic accuracy (TDA) was 86.1% in LOOCV. In the model to distinguish PSP, CBS, and MSA from LBD, the AUC/TDA values were 0.978/94.6%, 0.978/87.0%, and 0.880/80.3%, respectively. In the model to differentiate between CBS and MSA, MSA and PSP, and PSP and CBS, the AUC/TDA values were 0.967/91.3%, 0.920/88.0%, 0.875/77.8%, respectively. ConclusionAn image-based automated classification using striatal DAT activity and regional perfusion patterns provided a good performance in the differential diagnosis of neurodegenerative parkinsonian syndromes without clinical information.

A novel device for estimating olfactory threshold for differential diagnosis of parkinsonian syndrome: A pilot study

A novel device for estimating olfactory threshold for differential diagnosis of parkinsonian syndrome: A pilot study

Multivariate Analysis of 18F-DMFP PET Data to Assist the Diagnosis of Parkinsonism.

An early and differential diagnosis of parkinsonian syndromes still remains a challenge mainly due to the similarity of their symptoms during the onset of the disease. Recently, 18F-Desmethoxyfallypride (DMFP) has been suggested to increase the diagnostic precision as it is an effective radioligand that allows us to analyze post-synaptic dopamine D2/3 receptors. Nevertheless, the analysis of these data is still poorly covered and its use limited. In order to address this challenge, this paper shows a novel model to automatically distinguish idiopathic parkinsonism from non-idiopathic variants using DMFP data. The proposed method is based on a multiple kernel support vector machine and uses the linear version of this classifier to identify some regions of interest: the olfactory bulb, thalamus, and supplementary motor area. We evaluated the proposed model for both, the binary separation of idiopathic and non-idiopathic parkinsonism and the multigroup separation of parkinsonian variants. These systems achieved accuracy rates higher than 70%, outperforming DaTSCAN neuroimages for this purpose. In addition, a system that combined DaTSCAN and DMFP data was assessed.

CADA-computer-aided DaTSCAN analysis.

BackgroundDopamine transporter (DaT) imaging (DaTSCAN) is useful for the differential diagnosis of parkinsonian syndromes. Visual evaluation of DaTSCAN images represents the generally accepted diagnostic method, but it is strongly dependent on the observer’s experience and shows inter- and intra-observer variability. A reliable and automatic method for DaTSCAN evaluation can provide objective quantification; it is desirable for longitudinal studies, and it allows for a better follow-up control. Moreover, it is crucial for an automated method to produce coherent measures related to the severity of motor symptoms.MethodsIn this work, we propose a novel fully automated technique for DaTSCAN analysis that generates quantitative measures based on striatal intensity, shape, symmetry and extent. We tested these measures using a support vector machine (SVM) classifier.ResultsThe proposed measures reached 100 % accuracy in distinguishing between patients with Parkinson’s disease (PD) and control subjects. We also demonstrate the existence of a linear relationship and an exponential trend between pooled structural and functional striatal characteristics and the Unified Parkinson’s disease Rating Scale (UPDRS) motor score.ConclusionsWe present a novel, highly reproducible, user-independent technique for DaTSCAN analysis producing quantitative measures directly connected to striatum uptake and shape. In our method, no a priori assumption is required on the spatial conformation and localization of striatum, and both uptake and symmetry contribute to the index quantification. These measures can reliably support a computer-assisted decision system.Electronic supplementary materialThe online version of this article (doi:10.1186/s40658-016-0140-9) contains supplementary material, which is available to authorized users.

Cerebrospinal Fluid α-Synuclein In the Differential Diagnosis of Parkinsonian Syndromes

ABSTRACT: Aim: To evaluate the diagnostic value of the level of α-synuclein, DJ-1, and Alzheimer's disease markers in the cerebrospinal fluid (CSF) in patients with parkinsonian syndromes. Materials & methods: We measured α-synuclein, DJ-1 and Alzheimer's disease markers by quantitative immunoassays in 122 CSF samples from patients with Parkinson's disease (PD; n = 38), dementia with Lewy bodies (n = 20), multiple-system atrophy (n = 18), progressive supranuclear palsy (n = 28), corticobasal degeneration (n = 7), unspecified atypical parkinsonian disorders (n = 5) and healthy controls (n = 6). Results: The level of α-synuclein was significantly decreased in CSF from PD patients. For the total tau/α-synuclein ratio, we obtained an area under the curve of 0.80 of the receiver operating characteristics curve for the PD diagnosis. With a cut-off of 1.33, the tau/α-synuclein ratio had 93% diagnostic specificity at 75% sensitivity for PD. Conclusion: CSF α-synuclein measurement may be useful in the differential diagnosis of PD versus other parkinsonian syndromes. CSF α-synuclein is found at low levels in the CSF and requires specifically adjusted assays to be measured.

INTEREST OF EYE MOVEMENT ANALYSIS IN PARKINSONIAN SYNDROMES

Eye movement examination is useful in the differential diagnosis of parkinsonian syndromes, mainly to differentiate Parkinson9s disease from progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). To evaluate the contribution of oculomotricity to the diagnosis of patients with clinical suspicion of PSP or CBD, eye movements were recorded in 57 patients, including 28 patients with suspicion of PSP, 10 with suspicion of CBD, and 19 with an undetermined parkinsonian syndrome. Horizontal and vertical saccades, smooth pursuit and antisaccade task were recorded by video-oculography (eyeBrain system). Results from eye movement analysis were compared to the final clinical diagnosis. In 28 patients (49%), a symptomatic profile linked to PSP or CBD was obtained from oculomotor abnormalities. In 3 patients, we found supranuclear palsy at an early stage, whitout specific arguments for PSP. For 26 patients, oculomotricity was normal or non contributory. Oculomotricity abnormalities found in our PSP or CBD patients were similar to those describe in literature. Eye movement recording appears particularly helpful to guide the diagnosis of an atypical parkinsonian syndrome, or to rectify diagnosis between a border form of PSP or CBD. Eye movement recording is a non-invasive tool that can provide early information for the diagnosis of neurodegenerative disorders.

The utility of neuroimaging in the differential diagnosis of parkinsonian syndromes.

The differential diagnosis of parkinsonian syndromes can be challenging, particularly in early disease stages. However, prognosis and therapeutic regimes are not alike in Parkinson disease and atypical parkinsonism, and thus a correct diagnosis at the earliest possible stage is desirable. Over the past two decades, magnetic resonance imaging and radiotracer-based imaging techniques have proven to be helpful tools to enhance the accuracy of clinical diagnosis in these disorders. Here, we review recent advances in neuroimaging for the differential diagnosis of parkinsonian syndromes.

Tau protein, beta-amyloid1–42 and clusterin CSF levels in the differential diagnosis of Parkinsonian syndrome with dementia

BackgroundParkinson's disease (PD), PD with dementia (PDD) and Lewy body dementia (DLB) are synucleinopathies. PDD and DLB are sometimes considered a transition between PD and Alzheimer dementia (AD). Finding in vivo markers or their combination could help in the differential diagnosis of these neurodegenerative (ND) diseases. ObjectiveThe aim of this study was to assess cerebrospinal fluid (CSF) levels of tau protein, betaamyloid1–42 and clusterin and to compare these levels among patients with probable PD, PDD, DLB and AD. MethodsCSF levels of ND markers were assessed in 96 patients (27 patients with PD, 14 with PDD, 14 with DLB, 17 with AD and 24 subjects as a control group). ResultsIn all of the groups of patients, beta-amyloid1–42 levels were decreasing in the order PD>PDD>DLB>AD, whereas tau protein and the tau protein/beta-amyloid1–42 index were increasing in the same order (PD<PDD<AD), except for DLB. In paired group comparisons, higher levels of clusterin in PD patients (p=0.005) and PDD patients (p=0.052) compared to the CG were found. ConclusionThe results of the present study support the role of clusterin in PD pathogenesis. The decreasing CSF beta-amyloid1–42 levels in the order PDD, DLB and AD may relate to the increasing presence of AD pathology in these disorders.

Tau Protein, beta-Amyloid 1-42 and Clusterin CSF Levels in Differential Diagnosis of Parkinsonian Syndrome with Dementia (P04.156)

Tau Protein, beta-Amyloid 1-42 and Clusterin CSF Levels in Differential Diagnosis of Parkinsonian Syndrome with Dementia (P04.156)

Differential diagnosis of parkinsonian syndromes using F-18 fluorodeoxyglucose positron emission tomography

Positron emission tomography (PET) imaging with F-18 fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of regional glucose metabolism in patients with idiopathic Parkinson's disease (IPD) and the atypical parkinsonian syndromes of progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). We undertook this study to assess the utility of fluorodeoxyglucose-PET in the differential diagnosis of individual patients with clinical parkinsonism. "Visual" and "computer-supported" reading of the fluorodeoxyglucose-PET scans were used for image interpretation and compared with each other. One hundred thirty-six parkinsonian patients were referred from movement disorder clinics in specialty neurology centers for the fluorodeoxyglucose-PET study. Imaging-based diagnosis was obtained by visual assessment of individual scans by a PET physician blinded to the clinical diagnosis and also by computer-assisted interpretation using statistical parametric mapping (SPM) analysis. The results were compared with a 2-year follow-up clinical assessment made by a movement disorder specialist. Concordance of visual evaluation of fluorodeoxyglucose-PET with clinical diagnosis was achieved in 91.7% of patients scanned, 97.6% IPD, 80% MSA, 76.6% PSP, and 100% CBS. Blinded computer assessment using SPM was concordant with the clinical diagnosis in 91% of cases evaluated (90.4% IPD, 80% MSA, 93.3% PSP, and 100% CBS). Fluorodeoxyglucose-PET performed at the time of initial referral for parkinsonism is useful for the differential diagnosis of IPD, PSP, MSA, and CBS. Computer-assisted methods can be used for objective evaluation especially when expert readers are not available.

The Addenbrooke's Cognitive Examination for the differential diagnosis and longitudinal assessment of patients with parkinsonian disorders

ObjectiveDifferentiating idiopathic Parkinson's disease from atypical parkinsonian syndromes is challenging, especially in the early stages. We assessed whether the Revised Addenbrooke's Cognitive Examination (ACE-R) could differentiate between parkinsonian syndromes and...

Dopamine transporter imaging in clinically unclear cases of parkinsonism and the importance of Scans Without Evidence of Dopaminergic Deficit (SWEDDs)

The clinical diagnosis of Parkinson's disease (PD) is susceptible to misdiagnosis, especially in the earlier stages of the disease. Recently, in vivo imaging techniques assessing the presynaptic dopamine transporter (DAT) have emerged as a useful tool in PD diagnosis, improving its accuracy. It was to illustrate the clinical usefulness of a brain single-photon emission computed tomography (SPECT) DAT ligand, and highlight relevant aspects of scans without evidence of dopaminergic deficit (SWEDDs) in this context. We described four representative patients with clinically unclear parkinsonian syndromes who underwent [(99m)Tc]-TRODAT-1 SPECT and reviewed the clinical implications. DAT-SPECT is an important, cost-effective, technique for the differential diagnosis of parkinsonian syndromes. Additionally, SWEDD cases present clinical and paraclinical peculiarities that may retrospectively identify them as essential/dystonic tremor. The lack of histopathological data limits further conclusions.

Combined assessment of midbrain hyperechogenicity, hyposmia and motor asymmetry improves diagnostic accuracy in early Parkinson’s disease

Evaluation of: Busse K, Heilmann R, Kleinschmidt S et al. Value of combined midbrain sonography, olfactory and motor function assessment in the differential diagnosis of early Parkinson’s disease. J. Neurol. Neurosurg. Psychiatr. 83(4), 441–447 (2012).The differential diagnosis of Parkinsonian syndromes can be challenging, particularly in early disease stages, when overlapping clinical signs and symptoms may lead to erroneous classification. However, an early differentiation between Parkinson’s disease (PD) and other diseases causing Parkinsonism is crucial for prognostic and therapeutic reasons and is essential for clinical research. In a recent study, Busse et al. investigated the diagnostic utility of a set of tests to improve diagnostic differentiation between PD, essential tremor and other Parkinsonian disorders. The authors studied a total of 632 patients divided into a retrospective (n = 517) and a prospective (n = 115) group. Diagnostic anchors were based on clinical criteria. Combining midbrain hyperechogenicity, hyposmia and motor asymmetry increased specificity and positive predictive value for diagnosis of PD up to 98% at the expense of sensitivity, whereas two features provided 91% sensitivity with 77% specificity. The results of this study further support the diagnostic utility of transcranial sonography in diagnosing PD.

Transcranial sonography in Parkinson's disease

Transcranial sonography has become a useful tool in the differential diagnosis of parkinsonian syndromes. This is a non-invasive, low cost procedure. The main finding on transcranial sonography in patients with idiopathic Parkinson's disease is an increased echogenicity of the mesencephalic substantia nigra region. This hyperechogenicity is present in more than 90% of cases, and reflects a dysfunction in the dopaminergic nigrostriatal pathway. This study discussed how the hyperechogenicity of the substantia nigra may facilitate the differential diagnosis of parkinsonian syndromes.

Optical Coherence Tomography in Parkinsonian Syndromes

Background/ObjectiveParkinson's disease (PD) and the atypical parkinsonian syndromes multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are movement disorders associated with degeneration of the central nervous system. Degeneration of the retina has not been systematically compared in these diseases.MethodsThis cross-sectional study used spectral-domain optical coherence tomography with manual segmentation to measure the peripapillar nerve fiber layer, the macular thickness, and the thickness of all retinal layers in foveal scans of 40 patients with PD, 19 with MSA, 10 with CBS, 15 with PSP, and 35 age- and sex-matched controls.ResultsThe mean paramacular thickness and volume were reduced in PSP while the mean RNFL did not differ significantly between groups. In PSP patients, the complex of retinal ganglion cell- and inner plexiform layer and the outer nuclear layer was reduced. In PD, the inner nuclear layer was thicker than in controls, MSA and PSP. Using the ratio between the outer nuclear layer and the outer plexiform layer with a cut-off at 3.1 and the additional constraint that the inner nuclear layer be under 46 µm, we were able to differentiate PSP from PD in our patient sample with a sensitivity of 96% and a specificity of 70%.ConclusionDifferent parkinsonian syndromes are associated with distinct changes in retinal morphology. These findings may serve to facilitate the differential diagnosis of parkinsonian syndromes and give insight into the degenerative processes of patients with atypical parkinsonian syndromes.

Brain perfusion differences in Parkinsonian disorders

We aimed to objectively examine the brain perfusion differences between PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy. (99m) Tc ethylcysteinate dimer single-photon emission CT (SPECT) was performed in 28 patients with PD, 12 with Parkinson variant of multiple system atrophy, 19 with progressive supranuclear palsy, and 17 age- and sex-matched control subjects. A voxel-by-voxel group analysis, using statistical parametric mapping 8, was performed to detect the differences of regional cerebral blood flow among three diseases and control groups. Regional cerebral blood flow was measured using the noninvasive Patlak plot method and calculated using a fully automated region of interest technique. Progressive supranuclear palsy showed decreased regional cerebral blood flow in the cingulate gyrus and thalamus, whereas Parkinson variant of multiple system atrophy showed decreased regional cerebral blood flow in the cerebellum, compared with other patients and controls. Regional cerebral blood flow in the thalamus could be used to discriminate progressive supranuclear palsy from other diseases and control subjects with high sensitivity. These findings suggest that parkinsonian disorders, such as PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy show a distinct SPECT pattern in the frontal cortex, thalamus, and cerebellum. Moreover, the measurements of regional cerebral blood flow in the thalamus and cerebellum may be helpful in screening for the differential diagnosis of parkinsonian syndrome.

Differenzialdiagnose der Parkinson-Syndrome mittels MRT

The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in clinical neurology. Despite published consensus operational criteria for the diagnosis of Parkinson's disease (PD) and the various atypical parkinsonian disorders (APD), such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal degeneration (CBD), the clinical separation of APDs from PD carries a high rate of misdiagnosis. However, the early differentiation between APD and PD, each characterized by a very different natural history, is crucial for determining the prognosis and choosing a treatment strategy. Despite limitations the various modern magnetic resonance imaging (MRI) techniques have undoubtedly added to the differential diagnosis of neurodegenerative parkinsonism. In clinical practice conventional MRI with visual assessment of T2 and T1-weighted imaging is a well established method for the exclusion of symptomatic parkinsonism due to other pathologies and may also point to the diagnosis of APD. Furthermore, advances in MRI techniques, such as diffusion-weighted imaging (DWI), have enabled abnormalities in the basal ganglia and infratentorial brain structures in APD to be quantitatively illustrated.

Hyperechogenicity of the substantia nigra: pitfalls in assessment and specificity for Parkinson’s disease

During the last decade, substantia nigra (SN) hyperechogenicity has been established as a valuable supplementary diagnostic marker for Parkinson's disease. As an increasing number of studies indicate that this ultrasound feature may even be evident before motor symptoms of Parkinson's disease occur, longitudinal studies revealing its value as a screening instrument for subjects at risk are awaited with great expectancy. At the same time, other studies have shown that SN hyperechogenicity is not only found in Parkinson's disease but also in other disease entities. Limitations and pitfalls of the method need to be considered to evaluate and compare these studies. Taking these into account, it is important to realize that in some other neurodegenerative diseases as well as in disorders associated with an increased risk for Parkinson's disease hyperechogenicity can be found--usually, however, less prevalent. Interestingly, even in subgroups of patients with non-neurodegenerative disorders, SN hyperechogenicity can be detected. This holds, for example, true for multiple sclerosis patients with a higher rate of disease progression. In this disorder, microglia activation is known to occur, which is also evident in Parkinson's disease. This pathomechanism as well as increased iron content is known to contribute to SN hyperechogenicity. From the studies published so far it can be concluded that, although SN hyperechogenicity is not only found in Parkinson's disease, assessment of the echogenicity of the SN and other ultrasound features is valuable in the differential diagnosis of Parkinsonian syndromes and most probably in subjects at risk. Further elucidation of the cause of the echosignal will not only contribute to the understanding of the pathophysiology of some neurodegenerative diseases but also to an even better implementation in the clinical routine and for scientific studies.