Differential Diagnosis Of Neurodegenerative Parkinsonism Research Articles

Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy

[18F]fluorodeoxyglucose (FDG) PET and [123I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 ± 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson’s disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.

No effect of age, gender and total intracranial volume on brainstem MR planimetric measurements

ObjectivesMR planimetry of brainstem structures can be helpful for the discrimination of Parkinsonian syndromes. It has been suggested that ageing might influence brainstem MR measurements assessed by MR planimetry, while effects of gender and total intracranial volume (TIV) have not been assessed so far. The aim of this study was to evaluate age, gender and TIV effects on brainstem MR planimetric measures.MethodsBrainstem MR planimetric measures of diameters (midbrain, pons, middle and superior cerebellar peduncle) and areas (pons and midbrain), the derived ratios, and the magnetic resonance Parkinsonism index (MRPI) were assessed on 1.5-T MR images in a large cohort of 97 healthy controls and analysed for the influence of age, gender and TIV with univariate and multivariate linear models.ResultsNeither gender nor age effects on planimetric measurements were observed in the population relevant for the differential diagnosis of neurodegenerative Parkinsonism, aged 50 to 80 years, except for single area-derived measurements, with gender effects on pontine area (p = 0.013) and age effects on midbrain area (p = 0.037). Results were similar upon inclusion of the TIV in the analyses.ConclusionsThere is no need to correct for age, gender or TIV when using brainstem-derived MR planimetric measurements in the differential diagnosis of neurodegenerative Parkinsonism.Key Points• There were no gender effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for pontine area).• There were no age effects on single or combined imaging measurements of the brainstem in the population aged 50 to 80 years, the age range relevant for the differential diagnosis of neurodegenerative Parkinsonism (except for midbrain area).• There is no need for age- or gender-specific cut-offs for the relevant age group.

The diagnostic accuracy of the hummingbird and morning glory sign in patients with neurodegenerative parkinsonism

IntroductionThe hummingbird sign and the morning glory flower sign, reflecting midbrain pathology on MRI, have previously been shown to separate patients with progressive supranuclear palsy (PSP) from those with Parkinson's disease (PD) and multiple system atrophy (MSA). The aim of the present study was to determine the diagnostic accuracy and reproducibility of visual assessment of midbrain atrophy patterns in a large cohort of patients with neurodegenerative parkinsonism. MethodsRetrospective analysis of midbrain atrophy patterns on T1-weighted MRI in a large cohort of patients with neurodegenerative parkinsonism and healthy controls who underwent MR imaging during their diagnostic work-up. Results481 patients with neurodegenerative parkinsonism and 79 healthy controls were included in the present study. The presence of the hummingbird sign had a specificity of 99.5% and a positive predictive value of 96.1% for a diagnosis of PSP while sensitivity was suboptimal with 51.6%. Similarly, the presence of the morning glory flower sign yielded a specificity of 97.7% for a diagnosis of PSP, but sensitivity was only 36.8%. Sensitivity of both signs was 35.3% in early, clinically unclassifiable parkinsonism. Visual assessment of these midbrain alterations showed excellent inter-rater agreement. ConclusionMidbrain atrophy patterns are useful in the differential diagnosis of neurodegenerative parkinsonism but both the hummingbird sign and more so the morning glory flower sign suffer from low sensitivity, especially in early disease stages.

The putamen/caudate signal ratio of DaT-SPECT in differential diagnosis of neurodegenerative parkinsonism

The putamen/caudate signal ratio of DaT-SPECT in differential diagnosis of neurodegenerative parkinsonism

Update on SPECT and PET in parkinsonism - part 1: imaging for differential diagnosis.

To give an update on recent findings concerning the use of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) for differential diagnosis and prognosis of neurodegenerative parkinsonism and related disorders. Several studies confirmed the very high diagnostic accuracy and clinical impact of imaging nigrostriatal function (most notably with [I]FP-CIT-SPECT) for diagnosing neurodegenerative parkinsonism and dementia with Lewy bodies. Accurate differential diagnosis of neurodegenerative parkinsonism can be achieved by imaging disease-specific patterns of cerebral glucose metabolism with [18F]fluorodeoxyglucose-PET, which surpasses the diagnostic accuracy of other currently available radionuclide imaging techniques. SPECT and PET are established methods for the differential diagnosis of parkinsonism with significant therapeutic and prognostic impact. Given the limited accuracy of the clinical diagnosis as the reference standard, future studies with post-mortem verification are needed for validation of diagnostic imaging pattern, particularly in tauopathies.

Transcranial sonography and [18F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head‐to‐head comparison

Brain imaging with positron emission tomography using [(18) F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared. Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). After a median follow-up period of 9months, the final clinical diagnoses (reference standard) were Parkinson's disease, n=15; MSA, n=9; PSP, n=7; and CBD, n=5 (n=21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P=0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P=1.00). FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

A method for the visual analysis of early-stage Parkinson's disease based on virtual MRI-derived SPECT images

Objective: Nuclear medicine imaging of dopamine transporter (DAT) binding is used in the differential diagnosis of neurodegenerative Parkinsonism but DAT receptor density in the posterior part of the putamens is of difficult evaluation because it is strongly affected by the partial-volume effect. Since its quantitative correction is often difficult, we propose here a qualitative method to compare the real study to virtual images of the patient, obtained as if he/she was healthy. Method: The virtual images are obtained coregistering the magnetic resonance images to SPECT's; segmenting magnetic resonance images to obtain the real shape and position of caudates and putamens; digitally filling these volumes with an activity concentration close to normal condition; blurring and convolving images with the measured point-spread function of the SPECT system. Result: The method was applied to phantom and, retrospectively, to a small cohort of 20 patients, that underwent SPECT examination more than 3 years ago, to prove the feasibility of the method in a clinical environment. Conclusions: This method enhances the accuracy of the nuclear medicine interpretation by the inclusion of the proper morphological information of each patient, helping the physician to differentiate between partial-volume effects and real hypofixation of the tracer. The method proved to be feasible but is applicability is fostered by the need of a concomitant MR. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 172–176, 2012 © 2012 Wiley Periodicals, Inc.

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.

Biological fluid biomarkers in neurodegenerative parkinsonism

Patients with parkinsonian symptoms can present either to primary care physicians or to neurologists. In both contexts, differential diagnosis is problematic, particularly early in the disease when only subtle bradykinesia, rigidity or tremor is present. Adjunctive tests should help substantially to improve the accuracy of early clinical diagnosis. This Review appraises cerebrospinal fluid (CSF), plasma and urine biomarkers that have been studied in the differential diagnosis of neurodegenerative parkinsonism. CSF biomarkers seem to hold the most promise because of their intimacy with the degenerating neurons. Most assays are still in the early stages of development, but CSF measures of alpha-synuclein (specific for Parkinson disease) and tau fragments (specific for progressive supranuclear palsy) have been refined. Universal approval of these assays will depend on larger clinical trials and establishment of normal ranges. Other blood and CSF biomarkers have shown exceptional specificity and sensitivity when analyzed in combination, although these findings require verification. A host of potential biomarkers have, however, produced disappointing results, either because of poor specificity or low assay reproducibility. Despite such difficulties, improved technology, in conjunction with advances in nosology and pathology, means that biomarkers are poised to enter routine clinical practice to aid the differentiation of parkinsonian disorders.

MRI for the differential diagnosis of neurodegenerative parkinsonism in clinical practice

Parkinson's disease (PD) is the most common neurodegenerative cause of parkinsonism, followed by progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Despite the publication of consensus operational criteria for the diagnosis of PD and the various atypical parkinsonian disorders (APD) such as PSP, MSA and corticobasal degeneration, an accurate diagnosis of neurodegenerative parkinsonian syndromes remains a challenge for each neurologist. Particularly in the early disease stages the clinical separation of APDs from PD carries a high rate of misdiagnosis. However, an early differentiation between APD and PD, each characterized by completely different natural histories, is crucial for determining the prognosis and choosing a treatment strategy. MRI plays an important role in the exclusion of symptomatic parkinsonism due to other pathologies. Over the past two decades, conventional MRI and advanced MRI techniques, including proton magnetic resonance spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI), and magnetic resonance volumetry (MRV) have shown abnormalities in the substantia nigra and basal ganglia, especially in APD. Furthermore, in accordance with neuropathological studies suggesting that the olfactory system is an early target of the disease, recent studies using advanced MRI techniques have shown abnormalities in the olfactory system in the early disease stages of patients with PD. Given that olfactory deficits may be a premotor marker of the disease, such methods may eventually evolve into an early screening tool for PD.

An update on conventional and advanced magnetic resonance imaging techniques in the differential diagnosis of neurodegenerative parkinsonism

The clinical differentiation between Parkinson's disease and atypical parkinsonian disorders (APD) remains a challenge for every neurologist. Conventional magnetic resonance imaging (MRI) and different advanced MRI techniques offer the potential for objective criteria in the differential diagnosis of neurodegenerative parkinsonism. The aim of this article is to review the recent literature on the role of conventional and advanced MRI techniques in the differential diagnosis of neurodegenerative parkinsonian disorders. An important role of MRI is the exclusion of symptomatic parkinsonism due to other pathologies. Over the past two decades, conventional MRI and different advanced MRI techniques, including proton magnetic resonance spectroscopy (1H-MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and magnetic resonance volumetry (MRV) have been found to show abnormalities in the substantia nigra and basal ganglia, especially in APD. Recent studies using MRV, MTI, DWI and 1H-MRS to discriminate Parkinson's disease from APD are discussed extensively. Research findings suggest that novel MRI techniques such as MTI, DWI and MRV have superior sensitivity compared to conventional MRI in detecting abnormal features in neurodegenerative parkinsonian disorders. Whether these techniques will emerge as standard investigations in the work-up of patients presenting with parkinsonism requires further prospective magnetic resonance studies during early disease stages.

How to diagnose MSA early: the role of magnetic resonance imaging

The clinical differentiation between Parkinson's disease (PD) and multiple system atrophy (MSA) remains a challenge for each neurologist. The use of different magnetic resonance imaging (MRI) techniques including conventional MRI, proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and MR volumetry (MRV) offer the potential for objective criteria in the differential diagnosis of neurodegenerative parkinsonism. The aim of this article is to review the role of different MRI techniques in the differential diagnosis of PD and MSA.