Richardson's Syndrome Research Articles

Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be?

PSP is a pathologically defined neurodegenerative tauopathy with a variety of clinical presentations including typical Richardson's syndrome and other variant PSP syndromes. A large body of neuroimaging research has been conducted over the past two decades, with many studies proposing different structural MRI and molecular PET/SPECT biomarkers for PSP. These include measures of brainstem, cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in striatal dopamine imaging and, most recently, PET imaging with ligands that bind to tau. Our aim was to critically evaluate the degree to which structural and molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP. We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original research articles published in English over the past 20 years using postmortem diagnosis or the NINDS-SPSP criteria as the diagnostic standard from 1996 to 2016. We define a five-level theoretical construct for the utility of neuroimaging biomarkers in PSP, with level 1 representing group-level findings, level 2 representing biomarkers with demonstrable individual-level diagnostic utility, level 3 representing biomarkers for early disease, level 4 representing surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP biomarkers of PSP pathology. We discuss the degree to which each of the currently available biomarkers fit into this theoretical construct, consider the role of biomarkers in the diagnosis of Richardson's syndrome, variant PSP syndromes and autopsy confirmed PSP, and emphasize current shortfalls in the field. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society.

White matter and cortical changes in atypical parkinsonisms: A multimodal quantitative MR study

ObjectivesTo evaluate white matter and cortical changes in patients with parkinsonisms and healthy controls (HC), applying both hypothesis-free and regions of interest (ROI)-based advanced brain MR analyses. MethodsTwenty-five patients with Progressive Supranuclear Palsy - Richardson's Syndrome (PSP-RS), nine with cerebellar and nine with parkinsonian Multiple System Atrophy variants (MSA-C and MSA-P), forty-seven with Parkinson's Disease (PD) and twenty-seven HC underwent a 1.5 T brain-MR protocol including high-resolution 3D T1-weighted and 25-direction diffusion tensor imaging sequences. We performed cortical and white matter analysis by using vertex-based cortical thickness evaluation and Tract Based Spatial Statistics (TBSS), followed by a ROI-based cortical thickness analysis and probabilistic tractography of cortico-spinal tract (CST), and middle and superior cerebellar peduncles (MCP and SCP). ResultsIn PSP-RS, both ROIs-based and voxel-wise analyses demonstrated significant thinning of the pre-central cortices and diffuse white matter alterations involving supra- and infratentorial compartments. Along-tract tractography analysis of CST showed a significantly higher MD in PSP-RS vs PD and HC limited to the portion of the tract within the corona radiata. In MSA-C, a predominant involvement of MCPs was evident, while alterations in MCPs in MSA–P and in SCPs in PSP-RS and MSA-C were also present. ConclusionSpecific patterns of cortical and white matter changes in atypical parkinsonism patients reflect the neuropathological and clinical features of these disorders. This study shows that quantitative brain MR techniques can detect significant changes that help to elucidate the physiopathology of movement disorders and support their differential diagnosis.

Nonmotor Features in Atypical Parkinsonism.

Atypical parkinsonism (AP) comprises mainly multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which are distinct pathological entities, presenting with a wide phenotypic spectrum. The classic syndromes are now called MSA-parkinsonism (MSA-P), MSA-cerebellar type (MSA-C), Richardson's syndrome, and corticobasal syndrome. Nonmotor features in AP have been recognized almost since the initial description of these disorders; however, research has been limited. Autonomic dysfunction is the most prominent nonmotor feature of MSA, but also gastrointestinal symptoms, sleep dysfunction, and pain, can be a feature. In PSP and CBD, the most prominent nonmotor symptoms comprise those deriving from the cognitive/neuropsychiatric domain. Apart from assisting the clinician in the differential diagnosis with Parkinson's disease, nonmotor features in AP have a big impact on quality of life and prognosis of AP and their treatment poses a major challenge for clinicians.

A Fully Automated, Atlas-Based Approach for Superior Cerebellar Peduncle Evaluation in Progressive Supranuclear Palsy Phenotypes.

The superior cerebellar peduncle is damaged in progressive supranuclear palsy. However, alterations differ between progressive supranuclear palsy with Richardson syndrome and progressive supranuclear palsy-parkinsonism. In this study, we propose an automated tool for superior cerebellar peduncle integrity assessment and test its performance in patients with progressive supranuclear palsy with Richardson syndrome, progressive supranuclear palsy-parkinsonism, Parkinson disease, and healthy controls. Structural and diffusion MRI was performed in 21 patients with progressive supranuclear palsy with Richardson syndrome, 9 with progressive supranuclear palsy-parkinsonism, 20 with Parkinson disease, and 30 healthy subjects. In a fully automated pipeline, the left and right superior cerebellar peduncles were first identified on MR imaging by using a tractography-based atlas of white matter tracts; subsequently, volume, mean diffusivity, and fractional anisotropy were extracted from superior cerebellar peduncles. These measures were compared across groups, and their discriminative power in differentiating patients was evaluated in a linear discriminant analysis. Compared with those with Parkinson disease and controls, patients with progressive supranuclear palsy with Richardson syndrome showed alterations of all superior cerebellar peduncle metrics (decreased volume and fractional anisotropy, increased mean diffusivity). Patients with progressive supranuclear palsy-parkinsonism had smaller volumes than those with Parkinson disease and controls and lower fractional anisotropy than those with Parkinson disease. Patients with progressive supranuclear palsy with Richardson syndrome had significantly altered fractional anisotropy and mean diffusivity in the left superior cerebellar peduncle compared with those with progressive supranuclear palsy-parkinsonism. Discriminant analysis with the sole use of significant variables separated progressive supranuclear palsy-parkinsonism from progressive supranuclear palsy with Richardson syndrome with 70% accuracy and progressive supranuclear palsy-parkinsonism from Parkinson disease with 74% accuracy. We demonstrate the feasibility of an automated approach for extracting multimodal MR imaging metrics from the superior cerebellar peduncle in healthy subjects and patients with parkinsonian. We provide evidence that structural and diffusion measures of the superior cerebellar peduncle might be valuable for computer-aided diagnosis of progressive supranuclear palsy subtypes and for differentiating patients with progressive supranuclear palsy-parkinsonism from with those with Parkinson disease.

Prevalence of progressive supranuclear palsy in Yonago: change throughout a decade.

BackgroundProgressive supranuclear palsy (PSP) is a neurodegenerative disorder that is sometimes confused with Parkinson's disease, multiple system atrophy, and other disorders. The typical clinical features are categorized as Richardson's syndrome (RS), but other clinical subtypes include PSP‐parkinsonism (PSP‐P) and PSP‐pure akinesia with gait freezing (PSP‐PAGF). In this study, we determined the prevalence of PSP in a Japanese rural area compared to our previous 1999 report.MethodsWe collected data in Yonago City from 2009 to 2014 using a service‐based study of PSP. We collected case history data from PSP patients in the area from our hospital. The crude prevalence and 95% confidence interval (CI) were calculated using the population demographics on the prevalence day of 1 October 2010. Age‐ and sex‐adjusted prevalence was calculated by direct standardization to the population demographics in Yonago City on the prevalence day of 1 April 1999.Material and ResultsWe identified 25 patients: 16 with probable RS, 4 with possible RS, 3 with clinical PSP‐P, and 2 with clinical PSP‐PAGF. The prevalence per 100,000 was 17.90 (male = 18.05; female = 17.76). The prevalence of PSP in Yonago in 2010 increased compared to the measurements from 1999.ConclusionThe prevalence of PSP in Japan increased from 1999 to 2010.

Differentiation of neurodegenerative parkinsonian syndromes by volumetric magnetic resonance imaging analysis and support vector machine classification.

Clinical differentiation of parkinsonian syndromes is still challenging. A fully automated method for quantitative MRI analysis using atlas-based volumetry combined with support vector machine classification was evaluated for differentiation of parkinsonian syndromes in a multicenter study. Atlas-based volumetry was performed on MRI data of healthy controls (n = 73) and patients with PD (204), PSP with Richardson's syndrome phenotype (106), MSA of the cerebellar type (21), and MSA of the Parkinsonian type (60), acquired on different scanners. Volumetric results were used as input for support vector machine classification of single subjects with leave-one-out cross-validation. The largest atrophy compared to controls was found for PSP with Richardson's syndrome phenotype patients in midbrain (-15%), midsagittal midbrain tegmentum plane (-20%), and superior cerebellar peduncles (-13%), for MSA of the cerebellar type in pons (-33%), cerebellum (-23%), and middle cerebellar peduncles (-36%), and for MSA of the parkinsonian type in the putamen (-23%). The majority of binary support vector machine classifications between the groups resulted in balanced accuracies of >80%. With MSA of the cerebellar and parkinsonian type combined in one group, support vector machine classification of PD, PSP and MSA achieved sensitivities of 79% to 87% and specificities of 87% to 96%. Extraction of weighting factors confirmed that midbrain, basal ganglia, and cerebellar peduncles had the largest relevance for classification. Brain volumetry combined with support vector machine classification allowed for reliable automated differentiation of parkinsonian syndromes on single-patient level even for MRI acquired on different scanners. © 2016 International Parkinson and Movement Disorder Society.

The clinical spectrum and natural history of pure akinesia with gait freezing.

Gait freezing as a presenting and relatively restricted condition is uncommon but a distinctive disorder. This entity was initially defined as "pure akinesia with gait freezing", and later a neuropathological substrate of progressive supranuclear palsy has been recognized. Limited studies have reported the clinical evolution after presentation, which is important for patient counseling. The objective of this study was to assess the demographic and clinical features, treatment-response, neuroimaging, and evolution of pure akinesia with gait freezing. A retrospective review of patients with this phenotype as previously defined was performed. Patients included had no or minimal limb rigidity and/or bradykinesia and no resting tremor, and all underwent neuroimaging of the brain after onset. Inclusion criteria were met by 30 patients, who were followed up to 21years after symptom onset. During their course, 28 patients had falls (93%), 12 patients had dysarthria (40%), and 13 had handwriting changes (43%). All patients had progression of their gait disorder over time, but with a variable interval until falls occurred. None of the patients developed vertical gaze palsy or met diagnostic criteria for an alternative parkinsonian disorder. Pure akinesia with gait freezing is a distinctive disorder that can be recognized in the clinic. Despite the previously reported progressive supranuclear palsy-like neuropathology, the clinical course is much less aggressive and disabling than classic Richardson syndrome, although fall risk eventually develops in nearly all patients. Bradykinesia, tremor, and rigidity do not develop, distinguishing pure akinesia with gait freezing from Parkinson's disease and other parkinsonian disorders.

Differential Progression of Midbrain Atrophy in Parkinsonism: Longitudinal MRI Study

Aims: To elucidate different patterns of progression of midbrain atrophy in patients with Richardson's syndrome (RS), progressive supranuclear palsy-parkinsonism (PSP-P), and Parkinson's disease (PD) using magnetic resonance imaging (MRI)-based visual rating indexes. Methods: We recruited 12 patients with PSP-RS, 12 with PSP-P, and 23 with PD for whom MRIs had been followed up for at least 2 years (mean ± SD, 4.9 ± 1.6 years) after the initial MRI. MRI-based visual rating indexes were used to estimate midbrain atrophy, including the ratio of the pontine to midbrain tegmental areas (P/M ratio) on a midsagittal image, the length between the interpeduncular fossa and the center of the cerebral aqueduct at the midmammillary-body level (M^TEGM) on axial images, and the morning glory sign. Results: Initially, there were no differences in MRI-based visual rating indexes between PSP-P and PD, while PSP-RS showed a higher P/M ratio and lower M^TEGM compared with PSP-P and PD. In PD, the P/M ratio and M^TEGM remained stable with disease progression. However, the extent of changes between initial and follow-up indexes was similarly greater for both PSP-RS and PSP-P than for PD. Finally, PSP-P showed a higher P/M ratio and lower M^TEGM compared with PD in the follow-up, while PSP-RS still exhibited the most profound changes. Conclusions: Midbrain atrophy progresses differentially in patients with PSP-RS, PSP-P, and PD. Longitudinal measurements of midbrain atrophy using MRI-based visual rating indexes can help distinguish patients with PSP-P from those with PSP-RS and PD.

Cognitive impairment in progressive supranuclear palsy-Richardson’s syndrome is related to white matter damage

IntroductionBeside motor symptoms, patients with progressive supranuclear palsy syndrome (PSPs) commonly present cognitive and behavioral disorders. In this study we aimed to assess the structural brain correlates of cognitive impairment in PSPs. MethodsWe enrolled 23 patients with probable PSP Richardson's syndrome and 15 matched healthy controls. Patients underwent an extensive clinical and neuropsychological evaluation. Cortical thickness measures and diffusion tensor metrics of white matter tracts were obtained. Random forest analysis was used to identify the strongest MRI predictors of cognitive impairment in PSPs at an individual patient level. ResultsPSPs patients were in a moderate stage of the disease showing mild cognitive deficits with prominent executive dysfunction. Relative to controls, PSPs patients had a focal, bilateral cortical thinning mainly located in the prefrontal/precentral cortex and temporal pole. PSPs patients also showed a distributed white matter damage involving the main tracts including the superior cerebellar peduncle, corpus callosum, corticospinal tract, and extramotor tracts, such as the inferior fronto-occipital, superior longitudinal and uncinate fasciculi, and cingulum, bilaterally. Regional cortical thinning measures did not relate with cognitive features, while white matter damage showed a significant impact on cognitive impairment (r values ranging from −0.80 to 0.74). ConclusionsPSPs patients show both focal cortical thinning in dorsolateral anterior regions and a distributed white matter damage involving the main motor and extramotor tracts. White matter measures are highly associated with cognitive deficits. Diffusion tensor MRI metrics are likely to be the most sensitive markers of extramotor deficits in PSPs.

Finger tapping analysis in patients with Parkinson’s disease and atypical parkinsonism

The goal of this study was to investigate repetitive finger tapping patterns in patients with Parkinson’s disease (PD), progressive supranuclear palsy–Richardson syndrome (PSP-R), or multiple system atrophy of parkinsonian type (MSA-P). The finger tapping performance was objectively assessed in PD (n=13), PSP-R (n=15), and MSA-P (n=14) patients and matched healthy controls (HC; n=14), using miniature inertial sensors positioned on the thumb and index finger, providing spatio-temporal kinematic parameters. The main finding was the lack or only minimal progressive reduction in amplitude during the finger tapping in PSP-R patients, similar to HC, but significantly different from the sequence effect (progressive decrement) in both PD and MSA-P patients. The mean negative amplitude slope of −0.12°/cycle revealed less progression of amplitude decrement even in comparison to HC (−0.21°/cycle, p=0.032), and particularly from PD (−0.56°/cycle, p=0.001), and MSA-P patients (−1.48°/cycle, p=0.003). No significant differences were found in the average finger separation amplitudes between PD, PSP-R and MSA-P patients (pmsa-pd=0.726, pmsa-psp=0.363, ppsp-pd=0.726). The lack of clinically significant sequence effect during finger tapping differentiated PSP-R from both PD and MSA-P patients, and might be specific for PSP-R. The finger tapping kinematic parameter of amplitude slope may be a neurophysiological marker able to differentiate particular forms of parkinsonism.

A Review of Treatment Options for Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is an atypical parkinsonian condition characterized by a symmetric akinetic-rigid syndrome, early falls, supranuclear gaze palsy, and a frontotemporal behavioral syndrome. The typical phenotype is termed Richardson's syndrome, but numerous other phenotypes have been described. The pathophysiology of PSP is not fully understood, but dysfunction of the tau protein seems to play a central role. Despite exciting new knowledge on the pathophysiology of PSP, there is still no highly effective symptomatic or disease-modifying treatment. We review the evidence on pharmacotherapy and experimental therapies in PSP and provide levels of recommendation for the off-label use of commonly used drugs in this disorder.

Parkinsonism, movement disorders and genetics in frontotemporal dementia.

Frontotemporal dementia (FTD) refers to a group of clinically and genetically heterogeneous neurodegenerative disorders that are a common cause of adult-onset behavioural and cognitive impairment. FTD often presents in combination with various hyperkinetic or hypokinetic movement disorders, and evidence suggests that various genetic mutations underlie these different presentations. Here, we review the known syndromatic-genetic correlations in FTD. Although no direct genotype-phenotype correlations have been identified, mutations in multiple genes have been associated with various presentations. Mutations in the genes that encode microtubule-associated protein tau (MAPT) and progranulin (PGRN) can manifest as symmetrical parkinsonism, including the phenotypes of Richardson syndrome and corticobasal syndrome (CBS). Expansions in the C9orf72 gene are most frequently associated with familial FTD, typically combined with motor neuron disease, but other manifestations, such as symmetrical parkinsonism, CBS and multiple system atrophy-like presentations, have been described in patients with these mutations. Less common gene mutations, such as those in TARDBP, CHMP2B, VCP, FUS and TREM2, can also present as atypical parkinsonism. The most common hyperkinetic movement disorders in FTD are motor and vocal stereotypies, which have been observed in up to 78% of patients with autopsy-proven FTD. Other hyperkinetic movements, such as chorea, orofacial dyskinesias, myoclonus and dystonia, are also observed in some patients with FTD.

Progressive supranuclear palsy (PSP): Richardson syndrome and other PSP variants.

Phenotypic heterogeneity of progressive supranuclear palsy (PSP) has been increasingly reported in the literature and can be the source of incorrect clinical diagnosis particularly in the early stages of the disease when the classically associated symptoms of early falls and supranuclear gaze palsy may not be apparent. In addition to Richardson syndrome (RS), several atypical clinical phenotypes have been described. Advances in genetic, neuroimaging, and biochemical/molecular technologies contribute to the identification of these clinical subtypes in the context of typical PSP pathological findings. Our goal is to review the phenomenology reported in the literature that is associated with confirmed histopathological changes consistent with a PSP diagnosis and to highlight the clinical spectrum of PSP. A systematic review of the literature in PubMed through July 2015 using MeSH terms and key words related to PSP was conducted. Articles describing PSP classifications, diagnostic criteria, and case reports were reviewed and summarized. Additional PSP phenotypes not seen in recent clinicopathological studies are included. These include primary lateral sclerosis, pallido-nigro-luysian degeneration, axonal dystrophy, and multiple system atrophy in the spectrum of atypical PSP variants beyond the traditionally classified PSP subtypes. This review is intended to help with the diagnostic challenges of atypical PSP variants. We believe that large multicenter clinicopathological studies will help expand our understanding of etiology and specific mechanisms of neurodegeneration and will aid in the appropriate interpretation of outcomes when conducting clinical and basic science research.

Comparison of regional brain atrophy and cognitive impairment between pure akinesia with gait freezing and Richardson's syndrome

Pure akinesia with gait freezing (PAGF) is considered a clinical phenotype of progressive supranuclear palsy. The brain atrophy and cognitive deficits in PAGF are expected to be less prominent than in classical Richardson's syndrome (RS), but this hypothesis has not been explored yet. We reviewed the medical records of 28 patients with probable RS, 19 with PAGF, and 29 healthy controls, and compared cortical thickness, subcortical gray matter volume, and neuropsychological performance among the three groups. Patients with PAGF had thinner cortices in frontal, inferior parietal, and temporal areas compared with controls; however, areas of cortical thinning in PAGF patients were less extensive than those in RS patients. In PAGF patients, hippocampal, and thalamic volumes were also smaller than controls, whereas subcortical gray matter volumes in PAGF and RS patients were comparable. In a comparison of neuropsychological tests, PAGF patients had better cognitive performance in executive function, visual memory, and visuospatial function than RS patients had. These results demonstrate that cognitive impairment, cortical thinning, and subcortical gray matter atrophy in PAGF patients resemble to those in RS patients, though the severity of cortical thinning and cognitive dysfunction is milder. Our results suggest that, PAGF and RS may share same pathology but that it appears to affect a smaller proportion of the cortex in PAGF.

Interventions in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) an atypical parkinsonian with a common phenotype comprising early falls, the characteristic slowing of vertical saccades and a frontal syndrome with marked apathy (Richardson's syndrome). Currently, no effective symptomatic or neuroprotective treatment is available for PSP. Current medical have a limited role in PSP. Novel experimental treatments include davunetide or tideglusib, both inhibitors of glycogen synthase kinase-3 (GSK-3) that failed to improve the clinical outcome of PSP patients in two recent studies. Future interventions aiming at tau dysfunction and passive or active immunization are ongoing or underway.

Cerebral Peduncle Angle: An Objective Criterion for Assessing Progressive Supranuclear Palsy Richardson Syndrome.

Several criteria for time-consuming volumetric measurements of progressive supranuclear palsy Richardson syndrome subtype (PSP-RS) have been proposed. These often require image reconstruction in different planes for proper assessment. The purpose of this study was to evaluate the cerebral peduncle angle as a simple and reproducible measure of midbrain atrophy in patients with PSP-RS. The records of 15 patients with PSP-RS were retrospectively identified. The records of 31 age-matched healthy control subjects, 15 patients with multiple-system atrophy, and 22 patients with Parkinson disease were included for comparison. Two neuroradiologists individually assessed these studies for midbrain atrophy by evaluating the cerebral peduncle angle, that is, the angle between the two cerebral peduncles. The cerebral peduncle angle measurements were 62.1° (SD, 6.8°) in PSP-RS patients, 51.2° (SD, 10.1°) in healthy control subjects, 55.7° (SD, 11.6°) in patients with multiple-system atrophy, and 53.7° (SD, 8.5°) in patients with Parkinson disease. A statistically significant difference was found in the cerebral peduncle angle measurements (observer 1, p = 0.015; observer 2, p = 0.004) between the PSP-RS patients and the other subgroups. Bland-Altman analysis showed a bias of 0.6° (95% limits of agreement, 6.9°, -5.8°), and intraobserver variability analysis showed a bias of 0.5° (4.1°, -3°). The cerebral peduncle angle is a simple, easy-to-calculate, and reproducible measure of midbrain atrophy. It is a useful criterion for differentiating patients with PSP-RS from healthy persons and from patients with multiple-system atrophy or Parkinson disease.

Writing in Richardson variant of progressive supranuclear palsy in comparison to progressive non-fluent aphasia

BackgroundThe overlap between progressive supranuclear palsy (PSP) and progressive non-fluent aphasia (PNFA) is being increasingly recognized. In this paper descriptive writing in patients with Richardson syndrome of progressive supranuclear palsy (PSP-RS) is compared to writing samples from patients with PNFA. MethodsTwenty-seven patients participated in the study: 17 with the clinical diagnosis of PSP-RS and 10 with PNFA. Untimed written picture description was administered during neuropsychological assessment and subsequently scored by two raters blinded to the clinical diagnosis. Lexical and syntactic content, as well as writing errors (e.g. omission and perseverative errors) were analyzed. ResultsIn patients with PSP-RS both letter and diacritic mark omission errors were very frequent. Micrographia was present in 8 cases (47%) in PSP-RS group and in one case (10%) with PNFA. Perseverative errors did not differentiate between the groups. ConclusionsAs omission errors predominate in writing of patients with PSP-RS, writing seems to be compromised mainly because of oculomotor deficits, that may alter visual feedback while writing.

The contribution of cerebellar proton magnetic resonance spectroscopy in the differential diagnosis among parkinsonian syndromes.

The in vivo differential diagnosis between idiopathic Parkinson's disease (PD) and atypical parkinsonian syndromes (PS), such as multiple system atrophy [MSA with a cerebellar (C) and parkinsonian (P) subtype] and progressive supranuclear palsy - Richardson's Syndrome (PSP-RS) is often challenging. Previous brain MR proton spectroscopy ((1)H-MRS) studies showed biochemical alterations in PS, despite results are conflicting. Cerebellum plays a central role in motor control and its alterations has been already demonstrated in atypical PS. The main aim of this study was to evaluate diagnostic accuracy of cerebellar (1)H-MRS in the differential diagnosis between PD and atypical PS. We obtained (1)H-MRS spectra from the left cerebellar hemisphere of 57 PS (21 PD, and 36 atypical PS) and 14 unaffected controls by using a 1.5 T GE scanner. N-acetyl-aspartate (NAA)/Creatine (Cr), choline-containing compounds (Cho)/Cr, myoinositol (mI)/Cr, and NAA/mI ratios were calculated. NAA/Cr and NAA/mI ratios were significantly lower (p < 0.01) in atypical PS compared to PD and controls, and in MSA-C compared to PD, MSA-P, PSP-RS and controls. PSP-RS group showed reduced NAA/Cr ratios compared to PD (p < 0.05) and controls (p < 0.05), and reduced NAA/mI compared to controls (p < 0.01). NAA/Cr ratio values higher than 1.016 showed 100% sensitivity and negative predictive value, 62% positive predictive value and 64% specificity in discriminating PD. Cerebellar biochemical alterations detected by using (1)H-MRS could represent an adjunctive diagnostic tool to improve the differential diagnosis of PS.

Overlapping and distinguishing features of descriptive speech in Richardson variant of progressive supranuclear palsy and non-fluent progressive aphasia

Abstract Background Progressive supranuclear palsy (PSP) has overlapping clinical features with primary progressive aphasia (PPA). Our study aimed at comparing classical PSP phenotype – Richardson syndrome (PSP) with three different variants of PPA in terms of descriptive speech. Methods Fifty-eight patients participated in the study: 18 with the clinical diagnosis of PSP-RS, 14 with nfvPPA, eight with logopenic variant of PPA (lvPPA), 8 with semantic variant of PPA (svPPA) and 10 with Alzheimer's disease (AD). Results Lexical access in descriptive speech is comparably good in PSP-RS and nfvPPA. However, speech rate is faster in PSP-RS than in nfvPPA and patients with PSP-RS are more likely to construct complex sentences than individuals with nfvPPA. Conclusion Overlapping linguistic features were noted between PSP-RS and nfvPPA, but not with lvPPA or svPPA.