Features Of Progressive Supranuclear Palsy Research Articles

Clinical and neuroimaging characteristics of primary lateral sclerosis with overlapping features of progressive supranuclear palsy.

Primary lateral sclerosis (PLS) is a neurodegenerative disorder that primarily affects the central motor system. In rare cases, clinical features of PLS may overlap with those of progressive supranuclear palsy (PSP). We investigate neuroimaging features that can help distinguish PLS with overlapping features of PSP (PLS-PSP) from PSP. Six patients with PLS-PSP were enrolled between 2019 and 2023. We compared their clinical and neuroimaging characteristics with 18 PSP-Richardson syndrome (PSP-RS) patients and 20 healthy controls. Magnetic resonance imaging, 18F-flortaucipir positron emission tomography (PET), quantitative susceptibility mapping, and diffusion tensor imaging tractography (DTI) were performed to evaluate eight brain regions of interest. Area under the receiver operating characteristic curve (AUROC) was calculated. Five of the six PLS-PSP patients (83.3%) were male. Median age at symptom onset was 61.5 (52.5-63) years, and all had mixed features of PLS and PSP. Volumes of the pallidum, caudate, midbrain, and cerebellar dentate were smaller in PSP-RS than PLS-PSP, providing good discrimination (AUROC = 0.75 for all). The susceptibilities in pallidum, midbrain, and cerebellar dentate were greater in PSP-RS compared to PLS-PSP, providing excellent discrimination (AUROC ≥ 0.90 for all). On DTI, fractional anisotropy (FA) in the posterior limb of the internal capsule from the corticospinal tract was lower in PLS-PSP compared to PSP-RS (AUROC = 0.86), but FA in the superior cerebellar peduncle was lower in PSP-RS (AUROC = 0.95). Pallidum flortaucipir PET uptake was greater in PSP-RS compared to PLS-PSP (AUROC = 0.74). Regional brain volume, tractography, and magnetic susceptibility, but not tau-PET, are useful in distinguishing PLS-PSP from PSP.

Clinical Utility of Tectal Plate Measurements on Magnetic Resonance Imaging in Progressive Supranuclear Palsy.

Midbrain atrophy is a characteristic feature of progressive supranuclear palsy (PSP), observed in PSP-Richardson's syndrome (PSP-RS) and to a lesser extent PSP-parkinsonism (PSP-P). Our aim was to critically evaluate the utility of manual magnetic resonance imaging measurements of the midbrain tectal plate as a diagnostic biomarker in PSP. Length of the tectal plate and width of the superior and inferior colliculi were measured in 40 PSP (20 PSP-RS and 20 PSP-P) patients and compared with 20 Parkinson's disease and 20 healthy control subjects. Tectal plate length was reduced in both PSP groups compared with Parkinson's disease and control subjects and was most abnormal in PSP-RS followed by PSP-P. Reduced tectal plate length was associated with worse PSP Rating Scale scores. Simple manual measurements of tectal plate length show utility as a diagnostic biomarker in PSP, particularly for PSP-RS. © 2024 International Parkinson and Movement Disorder Society.

Clinical features of progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a clinically heterogenous atypical parkinsonian syndrome. Therefore, early recognition and correct diagnosis of PSP is challenging but essential. This study aims to characterize the clinical manifestations, magnetic resonance imaging (MRI), and longitudinal MRI changes of PSP in China. Clinical and MRI presentations were compared among 150 cases with PSP. Then the longitudinal MRI changes among 20 patients with PSP were further explored. Additionally, a series of midbrain-based MRI parameters was compared between PSP-P and PD. Throughout the course of the disease, there were differences in the symptoms of the fall and hand tremor between the PSP-RS and PSP-P. There were significant differences in the six midbrain-based MRI parameters between the PSP-RS and the PSP-P, including hummingbird sign, midbrain diameter, midbrain to pons ratio (MTPR), midbrain area, midbrain area to pons area ratio (Ma/Pa), and midbrain tegmental length (MBTegm). Longitudinal MRI studies revealed that the annual rel.ΔMTPR and rel.Δ (Ma/Pa) for PSP were 5.55 and 6.52%, respectively; additionally, PSP-RS presented a higher decline rate than PSP-P. Moreover, MTPR ≤0.56, midbrain diameter ≤ 0.92, midbrain area ≤ 1.00, and third ventricle width ≤ 0.75 could identify PSP-P from PD. PSP-P differs from PSP-RS regarding clinical manifestations, MRI, and longitudinal MRI changes. MRI parameters could be potential imaging markers to identify PSP-P from PD.

Sex differences for cognitive decline in progressive supranuclear palsy

IntroductionCognitive dysfunction is a core clinical feature of progressive supranuclear palsy (PSP), with executive function being most markedly affected. In other neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, there are a growing number of reports demonstrating that cognition is differentially impacted in men and women. In PSP, however, the sex differences in cognitive decline have yet to be fully characterized. MethodsData were obtained from the TAUROS trial for 139 participants with mild-to-moderate PSP (62 women, 77 men). Sex differences in longitudinal change in cognitive performance were evaluated with linear mixed models. Exploratory subgroup analyses assessed whether sex differences varied by baseline executive dysfunction, PSP phenotype, or baseline age. ResultsIn the primary whole group analyses, there were no sex differences for change in cognitive performance. Among participants with normal executive function at baseline, men declined more severely on executive function and language tests. Among the PSP-Parkinsonism subgroup, men declined more severely on category fluency. Across people aged≥65, men had a worse decline on category fluency, whereas across people aged <65, women had a worse decline on DRS construction. ConclusionIn people with mild-to-moderate PSP, there are no sex differences in cognitive decline. However, the rate of cognitive decline may differ for women and men based on the level of baseline executive dysfunction, PSP-phenotype and age. Further studies are needed to clarify how sex differences in PSP clinical progression vary by disease stage and to examine the contributions of co-pathology to these observed sex differences.

Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan (18F-APN-1607) revealed low-to-moderate uptake in the substantia nigra, globus pallidus, thalamus and posterior cortical areas, including temporal, parietal and occipital cortices. Neuropathological evaluation revealed widespread neuronal and glial tau pathology in cortical and subcortical structures, including tufted astrocytes in the motor cortex, striatum and midbrain tegmentum. The subthalamic nucleus had mild-to-moderate neuronal loss with globose neurofibrillary tangles, consistent with PSP. On the other hand, there were also astrocytic plaques, a pathological hallmark of CBD, in the neocortex and striatum. To further characterize the mixed pathology, we applied two machine learning-based diagnostic pipelines. These models suggested diagnoses of PSP and CBD depending on the brain region – PSP in the motor cortex and superior frontal gyrus and CBD in caudate nucleus. Western blots of insoluble tau from motor cortex showed a banding pattern consistent with mixed features of PSP and CBD, whereas tau from the superior frontal gyrus showed a pattern consistent with CBD. Real-time quaking-induced conversion (RT-QuIC) using brain homogenates from the motor cortex and superior frontal gyrus showed ThT maxima consistent with PSP, while reaction kinetics were consistent with CBD. There were no pathogenic variants in MAPT with whole genome sequencing. We conclude that this patient had an unclassified tauopathy and features of both PSP and CBD. The different pathologies in specific brain regions suggests caution in diagnosis of tauopathies with limited sampling.

Caídas frecuentes y neuroimágenes en paciente con parálisis supranuclear progresiva. Presentación de caso y revisión de la literatura

Las caídas en los adultos mayores son comunes, peligrosas y frecuentemente incapacitantes. Con frecuencia son multifactoriales y requieren un amplio abordaje diagnóstico. Las demencias, la enfermedad de Parkinson idiopática (EP), la enfermedad cerebrovascular y las neuropatías se encuentran entre las condiciones neurológicas que con mayor frecuencia se asocian a caídas. Sin embargo, cuando estas se presentan con recurrencia en el contexto de un síndrome parkinsoniano, particularmente al inicio de la enfermedad, deben sugerir el diagnóstico de una parálisis supranuclear progresiva (PSP). Esta entidad es de diagnóstico esencialmente clínico; sin embargo, dado su pronóstico sombrío, se realizan imágenes por resonancia magnética (IRM) de cerebro a todos los pacientes para excluir otros diagnósticos alternativos y buscar hallazgos característicos de PSP. Estos son, principalmente, atrofia del mesencéfalo, borramiento de la sustancia nigra, atrofia del putamen y atrofia con aumento de la señal del globo pálido.&#x0D; Se presenta a continuación el caso de un paciente adulto mayor que presentaba demencia y parkinsonismo refractario a levodopa, con caídas frecuentes, en quien la realización de una resonancia magnética sirvió para aclarar el diagnóstico al evidenciar los hallazgos típicos de PSP. Además, se hace una breve revisión de los principales hallazgos con imágenes, de demencias parkinsonianas, y la prevención de caídas en estos pacientes.

Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) has been reported as a disorder mainly characterized by a tendency to fall, vertical supranuclear gaze palsy, and constriction of the body axis, akinesia, and cognitive impairment. Patients presenting with these typical clinical features are diagnosed as having the PSP-Richardson syndrome (PSP-RS). Electronystagmography (ENG) is useful for the detection of ocular motility disorder, which is the main feature of PSP. In cases of PSP, ocular motility disorder in the vertical direction occurs from the initial stage of the disease, and is characterized by prolonged latency and reduced velocity of the saccadic eye movement in the vertical direction. Horizontal saccadic eye movement disorder also occurs after the intermediate stage. Square wave jerks (SWJ) are often recognized from the initial stage of the disease. In terms of nystagmus, the quick phase is impaired due to impaired saccadic eye movements, and impairment of optokinetic nystagmus also starts from the quick phase movements. Pursuit (smooth) eye movement may also be impaired as the disease progresses. On the other hand, the vestibulo-ocular reflex is maintained even after disease progression to a late stage.

Sex Differences for Verbal Fluency Decline in Progressive Supranuclear Palsy (P8-11.003)

<h3>Objective:</h3> To assess for sex differences in longitudinal change in verbal fluency performance in people with progressive supranuclear palsy (PSP). <h3>Background:</h3> Cognitive impairment is a core feature of PSP; executive dysfunction and reduced phonemic verbal fluency are included in the diagnostic criteria. Sex differences in other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, have been extensively studied with reports consistently showing cognition is differentially impacted in men and women. In PSP, however, the sex differences in cognitive decline have yet to be fully characterized. <h3>Design/Methods:</h3> We included 139 participants with PSP (62 women, 77 men) that underwent cognitive testing as part of the Tauros trial. Baseline sex differences in demographics and verbal fluency performance were assessed using Mann-Whitney U tests. Then, sex differences in longitudinal change in verbal fluency performance were evaluated with linear mixed models, including interactions of time and baseline score, age, and education as covariates. <h3>Results:</h3> There were no significant differences in baseline age, disease duration, and disease severity between women and men. Men had significantly more education than women (<i>p</i>=0.03). Baseline verbal fluency performance was similar across the sexes. However, compared to women, men had more severe decline in semantic fluency (β=−3.95±0.98; <i>p</i>=7.26e-5) and lexical fluency over time (β=−1.64±0.76; <i>p</i>=0.031). <h3>Conclusions:</h3> We found that men with PSP had worse decline in verbal fluency performance than women, suggesting PSP may affect cognition differently between sexes. Although studies in healthy elderly show a more pronounced decline in category fluency than letter fluency, our findings were likely not due to aging as these studies in healthy elderly report no sex differences for category fluency performance or rate of decline. As cognitive impairment is common and burdensome in PSP, sex-specific approaches may be needed to address the needs of people with PSP. <b>Disclosure:</b> Mr. Digma has nothing to disclose. Dr. Quijano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Litvan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. Dr. Bayram has nothing to disclose.

Loss of torsional quick eye movements during head roll in progressive supranuclear palsy: anew diagnostic marker.

Even though impaired horizontal and vertical saccades are well-known features of progressive supranuclear palsy (PSP), abnormalities of torsional quick phases of eye movements have not been defined in PSP and other Parkinsonian syndromes. This study aims to determine the diagnostic value of decreased torsional quick phases during head oscillations in the roll plane in patients with PSP. Using video-oculography, we recorded the head and eye motion during passive head oscillations in the roll plane and determined the decrease of torsional quick phases in patients with PSP (n = 13) in comparison to normal controls (n = 13) and those with multiple system atrophy (MSA, n = 17)or idiopathic Parkinson's disease (PD, n = 6). Torsional quick phases were absent during the torsional vestibulo-ocular reflex (VOR) in 78.6% (11/13) of the patients with PSP, but only in 11.8% (2/17) of those with MSA and none with idiopathic PD or of normal controls (Chi-square tests, p < 0.001) while gains of the torsional VOR did not differ among the groups (Chi-square tests, p > 0.05). Furthermore, the torsional quick phases were smaller even when observed in patients with PSP. Loss of torsional quick phases is an early biological marker for diagnosis of PSP, and may be ascribed to degeneration of the rostral interstitial nucleus of the medial longitudinal fasciculus that contains the burst neurons for torsional as well as vertical saccades.

Tauopathy, motricity and cognition

The tauopathies are one of the families of proteinopathies causing neurodegenerative diseases. They are characterized by a combination of cognitive and motor disorders. In this article, we summarize the clinical features of progressive supranuclear palsy and cortico-basal degeneration, focusing on their cognitive-behavioral impairment profiles, which in some cases allow them to be differentiated from other neurodegenerative entities. Finally, we propose tools for therapeutic management.

Linking molecular abnormalities to balance deficits using a zebrafish model for tauopathies

AbstractBackgroundThe ability to maintain balance is an evolutionarily‐conserved behavior that is frequently disrupted found in patients with neurodegenerative diseases. One of the most prominent balance disorders is found in patients with progressive supranuclear palsy (PSP), a primary tauopathy pathologically characterized by tau over‐representation in the brainstem vestibulospinal (VS) nucleus, where they frequently exhibit accidental‐backward falls starting from the early stage of the disease. Although pathological features of PSP correlate well with its clinical phenotype, how tau aggregation affects neuronal and circuit functions, which eventually leads to behavioral deficits, remains unclear.MethodTo dissect disease mechanisms across molecular, cellular, circuitry, and behavioral levels, we generated tau fish by expressing human 0N/4R‐Tau in zebrafish VS nucleus. Tau expression and phosphorylation were validated using immunohistochemistry staining with PHF‐1 antibody. To examine the effect of tau on balance behavior, we measured postural control of free‐swimming tau fish and compared to that of tau‐negative siblings. Moreover, we tested response of VS neurons to nose‐down and nose‐up tilt stimulus using 2‐photon calcium imaging.ResultTtau‐expressing zebrafish exhibit impaired balance control while maintaining normal locomotor ability. Interestingly, we did not observe any neuronal death in the VS nucleus. Functional imaging of the VS nucleus shows impaired directional tuning in tau‐expressing neurons in response to tilt stimulus. We also found ectopic accumulation of acidic organelles in the cell bodies of tau‐positive neurons, suggesting abnormal lysosomal function.ConclusionOur results demonstrate how molecular abnormalities disrupt specific behavior in tauopathies before neurodegeneration appeared.

Clinicopathological features of progressive supranuclear palsy with asymmetrical atrophy of the superior cerebellar peduncle.

Progressive supranuclear palsy (PSP) can be diagnosed despite the presence of asymmetrical parkinsonism depending on the clinical diagnostic criteria. Some studies have reported that atrophy of the superior cerebellar peduncle (SCP) is more frequent in PSP than in Parkinson's disease. There have also been reports of PSP cases with an asymmetrically atrophic SCP. Therefore, we analyzed 48 specimens from consecutive autopsy cases that were neuropathologically diagnosed as PSP to investigate the laterality of brain lesions, including the SCP. We measured the width of the SCP and evaluated the laterality of atrophy. We semi-quantitatively evaluated neuronal loss, atrophy/myelin pallor, and tau pathology in three steps. Asymmetrical atrophy of the SCP was present in seven (14.6%) of 48 cases. The atrophic side of the SCP corresponded to the dominant side of the tau pathology in the cerebellar dentate nucleus. It was opposite to the dominant side of the myelin pallor and tau pathology in the red nucleus and of the tau pathology in the central tegmental tract and inferior olivary nucleus, coinciding with the neurologically systematic anatomy of the Guillain-Mollaret triangle. Neurodegeneration of PSP can progress asymmetrically from one side to the initially intact side in PSP with an initial predominance of Richardson's syndrome, progressive gait freezing, ocular motor dysfunction, parkinsonism, or corticobasal syndrome. To our knowledge, no previous study has reported asymmetrical PSP neuropathology; this is the first study to report the presence of PSP cases with asymmetrical SCP atrophy and systematically asymmetrical degeneration of the Guillain-Mollaret triangle.

Epidemiology of Progressive Supranuclear Palsy: Real World Data from the Second Largest Health Plan in Israel.

Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative movement disorder and no disease modifying therapy (DMT) is currently available. This study aims to assess the epidemiology of PSP in Israel and to describe its clinical features. This retrospective analysis identified patients with PSP between 2000 and 2018 over the age of 40 years at first diagnosis (index date). We identified 209 patients with ≥1 diagnosis of PSP. Of those, 88 patients satisfied the inclusion criteria with a mean age at diagnosis of 72 years (SD = 8) and 53% were female. The 2018 prevalence and incidence rates were 5.3 and 1 per 100,000 persons, respectively. Median survival time was 4.9 years (95% CI 3.6–6.1) and median time from initial symptom to diagnosis was 4.2 years. The most common misdiagnoses were Parkinson’s disease, cognitive disorder and depression. The present study demonstrates that the clinic-epidemiological features of PSP in Israel are similar to PSP worldwide. In light of PSP’s rarity, investigation of PSP cohorts in different countries may create a proper platform for upcoming DMT trials.

Oculomotor abnormalities and its association with sleep stages in progressive supranuclear palsy

BackgroundOculomotor abnormalities are one of the cardinal clinical features of progressive supranuclear palsy (PSP). Vertical saccadic slowing is an early sign of PSP. The association between oculomotor abnormalities and sleep architecture has not been studied so far. ObjectivesTo study the association of oculomotor abnormalities of PSP with the sleep stages by using video polysomnography (vPSG). MethodsThis was a cross-sectional single-center study. Twenty-two patients with PSP and 15 age and gender-matched controls were recruited. Saccades, vestibulo-ocular reflex, and optokinetic nystagmus were assessed and graded clinically in all patients and one overnight vPSG was done in all cases. ResultsVertical saccades, upward more than downwards, were affected in all cases. While horizontal saccades were normal only in 41% of cases. Vertical optokinetic nystagmus (OKN) was affected in all cases. Horizontal OKN was normal in 36% of patients. The vertical upward saccades had a negative correlation with N1% and duration (r = −0.418; p = 0.05, r = −0.457; p = 0.03), N3% and duration (r = −0.486; p = 0.02, r = −0.510; p = 0.01), REM% (r = −0.449; p = 0.04), total sleep time (r = −0.487; p = 0.02) and sleep efficiency (r = −0.444; p = 0.04). There was a positive correlation between horizontal OKN and sleep onset latency (r = 0.432; p = 0.05). ConclusionsVertical saccadic restriction in PSP has significant negative correlation with total sleep time and sleep efficiency. The oculomotor and sleep abnormalities in PSP are probably interlinked and their assessment is useful in determining the characteristics of the disease.

Teaching Video NeuroImage: Tongue Tremor as a Presenting Feature of Progressive Supranuclear Palsy.

A 76-year-old man was referred to neurology by speech and language therapy after video fluoroscopy showed oropharyngeal dysphagia, aspiration, and tongue tremor (Video 1). He had presented with 6 months of progressive dysphagia, dysarthria, weight loss, and falls. Examination revealed akinetic rigidity, vertical supranuclear gaze palsy, slowed saccades, dysarthrophonia, and tongue tremor without palatal, jaw, or limb tremor. We diagnosed probable progressive supranuclear palsy (PSP). He did not respond to levodopa (400 mg/d). On a follow-up assessment 27 months later, the tremor persisted (Video 1). Tremor, usually upper limb, occurs in 42% of PSP cases.1 Isolated tongue tremor is a rare feature of PSP.1,2

A post‐mortem study of melanin‐concentrating hormone (MCH) neurons in Alzheimer’s disease and progressive supranuclear palsy: The complex degeneration pattern of the lateral hypothalamic area

AbstractBackgroundMelanin‐concentrating hormone neurons (MCH) are a key component of the subcortical brain circuits controlling sleep and wake states, and integrating them with other vital functions like motivated and feeding behavior into a 24‐hour circadian rhythm. Together with orexinergic neurons (OX), they represent the major neuronal population of the lateral hypothalamic area (LHA). Our group previously reported a profound degeneration of OX neurons in Alzheimer's disease (AD), and a reduction of OX production in progressive supranuclear palsy (PSP). In this report we provide for the first time a comprehensive and quantitative morphological study of MCH neurons in patients with AD, PSP and normal controls.MethodPost‐mortem human brain tissue of subjects with AD, PSP and controls was examined using unbiased stereology. Double immunohistochemistry with MCH‐ and tau‐antibodies on formalin‐fixed, celloidin embedded tissue was performed.ResultThere was no significant difference in the total number of MCH neurons between AD, PSP and controls, but a significant loss of non‐MCH neurons in AD patients (p=0.019). The proportion of MCH neurons was significantly higher in AD (p=0.0047). No such a difference was found in PSP. In PSP, but not AD, the proportion of tau+ MCH neurons was lower than the proportion of tau+ non‐MCH neurons (p=0.002). When comparing AD to PSP, the proportion of tau+MCH neurons was higher in AD (p&lt;0.001).ConclusionHigh burden of tau‐inclusions, but comparably milder loss of MCH neurons in AD, together with previously reported orexinergic neuronal loss may lead to a hyperexcitability of the MCH system in AD. This may contribute to the well‐known impairment of vigilance, reduction of NREM sleep and REM sleep disruption in AD. In contrast, we found virtually no involvement of MCH neurons in PSP, which reflects a specific vulnerability of these neurons to AD pathology. Clinically, PSP features a hyperarousal state, indicating that the activity of the arousal system prevails over a deficient sleep promoting system. We conclude that the involvement of other sleep promoting nuclei contributes to the insomnia in PSP. Further experimental research is needed to understand the molecular pathways involved in the specific vulnerability of MCH neurons in AD.

Segmental Alterations of the Corpus Callosum in Progressive Supranuclear Palsy: A Multiparametric Magnetic Resonance Imaging Study.

Background: The regional distribution of the widespread cerebral morphological alterations in progressive supranuclear palsy (PSP) is considered to include segmental parts of the corpus callosum (CC).Objective: The study was designed to investigate the regional white matter (WM) of the CC by T1 weighted magnetic resonance imaging (T1w MRI) data combined with diffusion tensor imaging (DTI) data in PSP patients, differentiated in the variants Richardson syndrome and PSP-parkinsonism, and to compare them with Parkinson’s Disease (PD) patients and healthy controls, in order to identify macro- and micro-structural alterations in vivo.Methods: MRI-based WM mapping was used to perform an operator-independent segmentation for the different CC segments in 66 PSP patients vs. 66 PD patients vs. 44 matched healthy controls. The segmentation was followed by both planimetric and texture analysis of the separated CC areas for the comparison of the three groups. Results were complemented by a DTI-based tract-of-interest analysis of the associated callosal tracts.Results: Significant alterations of the parameters entropy and homogeneity compared to controls were observed for PSP as well as for PD for the CC areas I, II, and III. The inhomogeneity in area II in the PSP cohort was the highest and differed significantly from PD. A combined score was defined as a potential marker for the different types of neurodegenerative parkinsonism; receiver operating characteristics (ROC) curves were calculated with areas under the curve values of 0.86 for PSP vs. controls, 0.72 for PD vs. controls, and 0.69 for PSP vs. PD, respectively.Conclusion: The multiparametric MRI texture and DTI analysis demonstrated extensive alterations of the frontal CC in neurodegenerative parkinsonism, whereas regional CC atrophy cannot be regarded as a constant neuroimaging feature of PSP. Specifically, the comparison PSP vs. PD revealed significant alterations in callosal area II. The combination of the texture and the DTI parameters might contribute as a neuroimaging marker for the assessment of the CC in PSP, including the differentiation vs. PD.

Human wildtype tau expression in cholinergic pedunculopontine tegmental neurons is sufficient to produce PSP-like behavioural deficits and neuropathology.

Progressive Supranuclear Palsy (PSP) is the most common atypical parkinsonism and exhibits hallmark symptomology including motor function impairment and dysexecutive dementia. In contrast to Parkinson's disease, the underlying pathology displays aggregation of the protein tau, which is also seen in disorders such as Alzheimer's disease. Currently, there are no pharmacological treatments for PSP, and drug discovery efforts are hindered by the lack of an animal model specific to PSP. Based on previous results and clinical pathology, it was hypothesized that viral deposition of tau in cholinergic neurons within the hindbrain would produce a tauopathy along neural connections to produce PSP-like symptomology and pathology. By using a combination of ChAT-CRE rats and CRE-dependent AAV vectors, wildtype human tau (the PSP-relevant 1N4R isoform; hTau) was expressed in hindbrain cholinergic neurons. Compared to control subjects (GFP), rats with tau expression displayed deficits in a variety of behavioural paradigms: acoustic startle reflex, marble burying, horizontal ladder and hindlimb motor reflex. Postmortem, the hTau rats had significantly reduced number of cholinergic pedunculopontine tegmentum and dopaminergic substantia nigra neurons, as well as abnormal tau deposits. This preclinical model has multiple points of convergence with the clinical features of PSP, some of which distinguish between PSP and Parkinson's disease.

Assessment of frontal lobe functions in Parkinsonism syndromes

Frontal lobe dysfunction is a predominant feature of progressive supranuclear palsy however it can be present in other parkinsonism syndromes also. The frontal assessment battery (FAB) is a brief tool developed to assess frontal lobe functioning at bedside Objective: To assess the frontal lobe functions in patients with Parkinsonism syndromes.

A case report of Multi System Atrophy (MSA) with cross over features of Progressive Supranuclear Palsy (PSP)

A case report of Multi System Atrophy (MSA) with cross over features of Progressive Supranuclear Palsy (PSP)