Biomedical subjects

Dominic Paviour

Publications and source records attributed to Dominic Paviour.

3 recordsLinked to original sources

PubMed2004

The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations.

Multiple system atrophy (MSA) has varying clinical (MSA-P versus MSA-C) and pathological [striatonigral degeneration (SND) versus olivopontocerebellar atrophy (OPCA)] phenotypes. To investigate the spectrum of clinicopathological correlations, we performed a semi-quantitative pathological analysis of 100 MSA cases with well-characterized clinical phenotypes. In 24 areas, chosen from both the striatonigral (StrN) and olivopontocerebellar (OPC) regions, the severity of neuronal cell loss and gliosis as well as the frequency of glial (oligodendroglial) cytoplasmic inclusions (GCIs) and neuronal cytoplasmic inclusions (NCIs) were determined. Clinical information was abstracted from the patients' medical records, and the severity of bradykinesia in the first year of disease onset and in the final stages of disease was graded retrospectively. The degree of levodopa responsiveness and the presence or absence of cerebellar ataxia and autonomic symptoms were also recorded. We report that 34% of the cases were SND- and 17% were OPCA-predominant, while the remainder (49%) had equivalent SND and OPCA pathology. We found a significant correlation between the frequency of GCIs and the severity of neuronal cell loss, and between these pathological changes and disease duration. Our data also suggest that GCIs may have more influence on the OPC than on the StrN pathology. Moreover, we raise the possibility that a rapid process of neuronal cell loss, which is independent of the accumulation of GCIs, occurs in the StrN region in MSA. There was no difference in the frequency of NCIs in the putamen, pontine nucleus and inferior olivary nucleus between the SND and OPCA subtypes of MSA, confirming that this pathological abnormality is not associated with a particular subtype of the disease. In the current large post-mortem series, 10% of the cases had associated Lewy body pathology, suggesting that this is not a primary process in MSA. As might be expected, there was a significant difference in the severity of bradykinesia and the presence of cerebellar signs between the pathological phenotypes: the SND phenotype demonstrates the most severe bradykinesia and the OPCA phenotype the more frequent occurrence of cerebellar signs, confirming that the clinical phenotype is dependent on the distribution of pathology within the basal ganglia and cerebellum. Putaminal involvement correlated with a poor levodopa response in MSA. Our finding that relatively mild involvement of the substantia nigra is associated clinically with manifest parkinsonism, while more advanced cerebellar pathology is required for ataxia, may explain why the parkinsonian presentation is predominant over ataxia in MSA.

Adult↗

PubMed2004

Punding in Parkinson's disease: its relation to the dopamine dysregulation syndrome.

Punding is a term that was coined originally to describe complex prolonged, purposeless, and stereotyped behaviour in chronic amphetamine users. A structured interview of 50 patients with higher dopamine replacement therapy requirements (>800 levodopa equivalent units/day) from 123 unselected patients with Parkinson's disease (PD) from a PD clinic identified 17 (14%) patients with punding. Punding was acknowledged as disruptive and unproductive by the patients themselves, but forcible attempts by family to interrupt the behaviour led to irritability and dysphoria. Punding was associated with very high doses of dopamine replacement therapy often related to a pattern of chronic inappropriate overuse of dopaminergic medication. We believe that this is an underreported, socially disabling phenomenon that is commonly associated with the syndrome of dopamine dysregulation and is phenomenologically distinct from both obsessive-compulsive disorder and mania.

Aged↗

PubMed2004

Voxel-based morphometry detects patterns of atrophy that help differentiate progressive supranuclear palsy and Parkinson's disease.

Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) are neurodegenerative diseases with distinctive pathological appearances. Early clinical diagnosis can be difficult. MRI may help differentiate PSP from PD, but the differences are often only obvious with advanced disease. It would be useful to have an unbiased assessment of difference to guide visual assessment of MRI as an aid to clinical diagnosis. Voxel-based morphometry (VBM) offers nonbiased, observer-independent morphometric MRI analysis. Our objectives were to assess structural differences between PSP, PD, and normal controls and test the clinical utility of the results. T1-weighted MR images in 12 patients with clinically diagnosed PSP, 12 with PD, and 12 age- and sex-matched controls were normalized to a common stereotaxic space and segmented into gray matter (GM) and white matter (WM) then analyzed using VBM. MRI scans were reviewed by a neuroradiologist blinded to the clinical diagnosis and assigned to the "non-PSP" or "PSP" group based on regional differences highlighted using VBM. VBM revealed significant group differences between PSP and PD as well as PSP and controls, with tissue reduction demonstrated in the region of the cerebral peduncles and midbrain. With these regional differences as a guide, neuroradiological diagnosis achieved a sensitivity of 83% and a specificity of 79%. VBM did not detect dramatic changes in frontal regions despite significant frontal cognitive decline in the PSP group. Pathology in the basal ganglia rather than tissue loss in the frontal lobes could be responsible for this. This information may help in the differentiation of PSP in clinical practice.

Aged↗