PSP-Richardson's Syndrome Research Articles

Abnormal ghrelin secretion contributes to gastrointestinal symptoms in multiple system atrophy patients

Patients with multiple system atrophy (MSA) often have evidence of compromised gastrointestinal motility. Ghrelin is a gut hormone that influences gastrointestinal motility in humans. The aim of this study was to determine whether ghrelin secretion is affected in MSA patients, and to investigate the relation between ghrelin secretion and gastrointestinal symptoms. Plasma levels of active ghrelin and unacylated ghrelin were measured in patients with MSA (n = 30), other atypical parkinsonian disorders including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome (n = 24), and control subjects (n = 24) using enzyme-linked immunosorbent assays. Gastrointestinal symptoms were quantified in all subjects using a self-report questionnaire. The ratio of active ghrelin to total ghrelin in the plasma (active ghrelin ratio) was lower in patients with MSA (mean: 8.0 %) than in patients with other atypical parkinsonian disorders (mean: 13.7 %, P = 0.001) and control subjects (mean: 13.9 %, P = 0.001). The active ghrelin ratio was correlated with the severity of gastrointestinal symptoms in MSA (r = −0.5, P = 0.004). Our observations indicate that ghrelin secretion is affected in patients with MSA. The low active ghrelin ratio may contribute to gastrointestinal symptoms in MSA.

Diffusivity of Cerebellar Hemispheres Enables Discrimination of Cerebellar or Parkinsonian Multiple System Atrophy from Progressive Supranuclear Palsy–Richardson Syndrome and Parkinson Disease

To explore the usefulness of histogram analysis of mean diffusivity (MD) derived from diffusion-weighted imaging of large infratentorial structures to distinguish parkinsonian syndromes. Local research ethics committee approval and informed consent were obtained. Ten patients with Parkinson disease (PD), nine with the parkinsonian variant of multiple system atrophy (MSA-P), seven with the cerebellar variant of MSA (MSA-C), 17 with progressive supranuclear palsy-Richardson syndrome (PSP-RS), and 10 healthy subjects were recruited. Histograms of MD values were generated for all pixels in the whole infratentorial compartment and separately for the whole brainstem, vermis, and cerebellar hemispheres. To assess the differences in MD values among groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney U test for pairwise comparisons. All P values resulting from pairwise comparisons were corrected with the Bonferroni method. MSA-P and MSA-C groups had higher median MD values (P < .01) in the brainstem and cerebellum when compared with other groups; this finding was in line with the known consistent neurodegenerative damage in posterior cranial fossa structures in these diseases. Median MD values from cerebellar hemispheres were used to discriminate patients with MSA-C and those with MSA-P from patients with PD and those with PSP-RS (P < .01; sensitivity, specificity, and positive predictive value equaled 100%). Furthermore, patients with PSP-RS had significantly higher MD values in the vermis than did healthy subjects (P < .05) and patients with PD (P < .001). These findings support the clinical usefulness of diffusion imaging in the differential diagnosis of parkinsonism, suggesting that the minimally operator-dependent histogram analysis of the infratentorial structures and particularly of the whole cerebellar hemispheres can be used to distinguish patients with MSA-P and those with MSA-C from patients with PSP-RS and those with PD.

Progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy which can manifest clinically in a variety of syndromes. In this review, the classic and most common variant syndrome -PSP-Richardson's syndrome (PSP-RS) -is the focus, with the core clinical features, varying cognitive/motor/neuropsychiatric/sleep manifestations, neuropsychological findings, and typical neuroimaging findings all reviewed. Management strategies are also discussed. Of particular interest are the recently commenced clinical trials involving agents which affect key steps in the presumed pathogenesis of the tauopathies. The distinctive and recognizable characteristics of PSP-RS and advent of clinical trials involving potential disease modifying agents underscore the importance of identifying patients with this disorder and encouraging their involvement in trials.

Cortical atrophy differentiates Richardson's syndrome from the parkinsonian form of progressive supranuclear palsy

To determine whether brain atrophy differs between the two subtypes of progressive supranuclear palsy (PSP), Richardson's syndrome (PSP-RS), and PSP parkinsonism (PSP-P), and whether such atrophy directly relates to clinical deficits and the severity of tau deposition. We compared 24 pathologically confirmed PSP cases (17 PSP-RS and 7 PSP-P) with 22 controls from a Sydney brain donor program. Volume loss was analyzed in 29 anatomically discrete brain regions using a validated point-counting technique, and tau-immunoreactive neurons, astrocytes and oligodendrocytes/threads semiquantified. Correlations between the two pathological measures and the presence or absence of cardinal PSP symptoms were investigated. Cortical atrophy was more severe in PSP-RS than PSP-P and affected more frontal lobe regions (frontal pole, inferior frontal gyrus). The supramarginal gyrus was atrophic in both subtypes. Additionally, atrophy of the internal globus pallidus, amygdala, and thalamus was more severe in PSP-RS. As expected, more severe frontal lobe tau pathology differentiated PSP-RS from PSP-P. No correlations were found between the degree of atrophy and severity of tau pathology in any region assessed, or between the severity of atrophy or tau pathology and the presence or absence of cardinal PSP symptoms. Our study shows that thalamocortical atrophy is a defining feature of PSP-RS, but this atrophy does not correlate with the presence of any specific cardinal clinical feature. Interestingly, there is a disassociation between tau pathology and atrophy in the brain regions affected in PSP-RS that requires further investigation.