1/29. Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p.The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-synuclein as a component of lewy bodies has heralded a new era in the study of Parkinson's disease. We have identified a large family with Lewy body parkinsonism linked to a novel locus on chromosome 4p15 that does not have a mutation in the alpha-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight alpha-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology. Distinctive histopathology was revealed with alpha-synuclein immunostaining, including pleomorphic lewy bodies, synuclein-positive glial inclusions and widespread, severe neuritic dystrophy. We also discuss the relationship of this familial disorder to a lewy body disease clinical spectrum, ranging from Parkinson's disease to dementia with psychosis.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
2/29. Brainstem-type lewy body disease presenting with progressive autonomic failure and lethargy.The authors report an autopsy case characterized by progressive lethargy and autonomic failure with a distinctive pattern of occurrence of lewy bodies. Autonomic dysfunction such as sleep apnea, orthostatic hypotension, dysuria, and hypohidrosis predominated with lethargy, whereas parkinsonism was not apparent. Numerous lewy bodies were widely evident microscopically in brainstem nuclei and the intermediolateral cell columns of the spinal cord, as well as in the sympathetic ganglia, but were rare or absent in the cerebral cortex and other supratentorial structures. Marked neuronal loss was seen in the locus ceruleus, raphe nuclei, dorsal vagal nuclei, and intermediolateral cell columns, but neurons in the substantia nigra, other brain regions, and sympathetic ganglia appeared undiminished. This case represents a specific clinicopathologic form of lewy body disease occurring predominantly in the brainstem, spinal cord, and sympathetic ganglia.- - - - - - - - - - ranking = 1.5keywords = brain (Clic here for more details about this article) |
3/29. dementia with lewy bodies: a pure case.A pure case of autopsy-confirmed dementia with lewy bodies (DLB) is described. The patient presented with distinctive verbal fluency deficits in the context of mild language impairment, intact recognition memory, and impaired paragraph recall. neuroimaging (CT and SPECT) showed progressive medial temporal lobe atrophy. Neuropathology revealed lewy bodies, degeneration in the substantia nigra, nucleus basalis of Meynert (Nakano & Hirano, 1984), and locus ceruleus, but no pathology characteristic of Alzheimer's disease. It is in this sense that the case is "pure" DLB. Early neuropsychological diagnosis of DLB is essential (salmon et al., 1996) given the potentially fatal hazard of neuroleptics (McKeith et al., 1992) and the difficulties associated with clinical neurological diagnoses (Litvan et al., 1998).- - - - - - - - - - ranking = 0.42313746732415keywords = atrophy (Clic here for more details about this article) |
4/29. The pathology of rem sleep behavior disorder with comorbid Lewy body dementia.A patient with rem sleep behavior disorder who subsequently developed probable Lewy body dementia is now reported to have a definite pathologic diagnosis of Lewy body dementia. Examination of brain revealed lewy bodies as well as marked neuronal loss in brainstem monoaminergic nuclei-particularly locus coeruleus and substantia nigra-that inhibit cholinergic neurons in the pedunculopontine nucleus mediating atonia during REM sleep.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
5/29. dementia with lewy bodies studied with positron emission tomography.OBJECTIVE: To report a case initially fulfilling the clinical criteria for probable alzheimer disease, although later clinical features suggested dementia with lewy bodies. oxygen 15-labeled positron emission tomograms revealed a pattern of hypometabolism characteristic of alzheimer disease. At post mortem, there was no evidence of the pathological features of alzheimer disease, but diffuse cortical lewy bodies were seen in the pigmented brainstem nuclei and cerebral cortex. DESIGN: A case report. SETTING: Tertiary referral center. PATIENT: A 65-year-old white man presented with a 3-year history of memory loss and language difficulties. RESULTS: oxygen 15-labeled positron emission tomograms revealed hypometabolism in the frontal, temporal, and parietal lobes, more severe on the left than right. metabolism in the left caudate was just outside the 95% reference range. Occipital metabolism was normal. CONCLUSIONS: Positron emission tomographic studies have been reported to show occipital hypometabolism in dementia with lewy bodies, in addition to the characteristic posterior bitemporal biparietal pattern of alzheimer disease. We suggest that although this finding may favor a diagnosis of dementia with lewy bodies, it is not necessary for diagnosis.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
6/29. dementia with lewy bodies and Alzheimer's disease.To investigate similarities and differences between Alzheimer's disease (AD) and dementia with lewy bodies (DLB), we undertook a demographic analysis of 277 patients from the Kathleen Price Bryan brain Bank with an antemortem diagnosis of probable AD. patients with additional, possibly confounding clinical and pathologic diagnoses such as infarcts, hematomas, neoplasms, and other neurodegenerative disorders, were excluded from the analysis. Neuropathologically, AD alone was present in 192 subjects (69%), and DLB was found in 85 subjects (31%). All of the DLB cases had neuropathologic evidence of AD sufficient to meet CERAD criteria for a diagnosis of definite AD plus nigral lewy bodies. Gender, apolipoprotein E (APOE) genotype, brain weight, age at death, duration of disease and Braak stage were compared between the two groups. Statistical analyses were performed using Fisher's exact test for comparisons of categorical data and Student's t-test for comparison of means for continuous outcomes. The proportion of males and females was balanced in the combined AD and DLB populations. There was a highly statistically significant increased frequency of APOE 3/4 in males with DLB (P = 0.007). We found higher brain weights in males with DLB versus males with AD (P = 0.012). AD was more frequent in females and DLB was more frequent in males (P = 0.019). Our findings with respect to age at death, duration of disease and Braak stage within diagnostic groups confirm previously reported findings. These data suggest that lewy bodies are more common in males affected with dementia, especially those with the APOE 3/4 genotype.- - - - - - - - - - ranking = 1keywords = brain (Clic here for more details about this article) |
7/29. Familial diffuse lewy body disease, eye movement abnormalities, and distribution of pathology.BACKGROUND: Familial diffuse lewy body disease (DLBD) is rare and not yet associated with a defect in the synuclein gene. In the differential diagnosis of the parkinsonian syndromes, defects in vertical gaze tend to be identified with progressive supranuclear palsy. False-positive diagnosis of progressive supranuclear palsy can occur, and defects in vertical gaze have been reported in DLBD, although so far a pure vertical gaze palsy associated with pathological abnormalities in the substrate for vertical gaze has not been described. OBJECTIVES: To report the clinical and pathological findings in 2 siblings with DLBD, and to relate the distribution of the pathological abnormalities in the brainstem to centers for vertical gaze. MATERIALS: For several years, 2 Irish siblings experienced a progressive parkinsonism-dementia complex associated in one with a defect in vertical gaze and in both with visual hallucinations. RESULTS: In both patients, results of pathological examination revealed (1) Lewy bodies positive for ubiquitin and alpha-synuclein together with cell loss and gliosis in the substantia nigra, locus ceruleus, and neocortex; and (2) similar findings in the rostral interstitial nucleus of the medial longitudinal fasciculus, the posterior commissure, and the interstitial nucleus of Cajal (substrates for vertical gaze). CONCLUSIONS: Familial DLBD (not shown to be genetically as distinct from environmentally transmitted) has been shown to exist in an Irish family. Caution should be enjoined in the interpretation of defects in vertical gaze in the differential diagnosis of the parkinsonian syndromes.- - - - - - - - - - ranking = 0.5keywords = brain (Clic here for more details about this article) |
8/29. An imaging study of parkinsonism among African-Caribbean and Indian london communities.We previously reported on 131 parkinsonian patients of African-Caribbean and Indian origin attending movement disorders clinics in six london hospitals, of whom approximately 20% manifested atypical parkinsonism with a late-onset, akinetic-rigid predominant syndrome, postural instability and minimal resting tremor refractory to levodopa therapy and dopamine agonists (see Hu et al., neurology 2000;54[Suppl.3]: A188 and Hu et al., Mov Disord 2000;15[Suppl.3]:S212). To better elucidate the phenotype of these atypical patients (18)FDG/(18)F-dopa positron emission tomography (PET) were performed in a subgroup to look for cortical and striatal metabolic changes suggestive of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or dementia with lewy bodies. magnetic resonance imaging (MRI) rating of cerebral vascular lesion load, putaminal atrophy, and neuropsychological testing were also performed. Discriminant function analysis of (18)F-dopa/(18)FDG striatal metabolism in 43 patients failed to separate atypical ethnic minority from typical Caucasian Parkinson's disease (PD) patients. Additionally, atypical Indian and African-Caribbean patients did not show cortical reductions in glucose metabolism suggestive of PSP, CBD, or DLB. Cerebral vascular lesion load rated in these patients did not differ between atypical and typical PD groups, and none of the atypical patients had MRI changes suggestive of MSA or PSP. Our results suggest the atypical parkinsonian phenotype seen in African-Caribbean and Indian patients represents a levodopa-refractory form of PD separate from MSA or PSP in most patients.- - - - - - - - - - ranking = 0.84627493464829keywords = atrophy (Clic here for more details about this article) |
9/29. dementia with lewy bodies showing advanced Lewy pathology but minimal Alzheimer pathology--Lewy pathology causes neuronal loss inducing progressive dementia.The present study concerns an autopsied case of dementia with lewy bodies (DLB) showing advanced Lewy pathology but minimal Alzheimer pathology. The patient was a 50-year-old Japanese male without inheritance. His initial symptoms at the age of 43 suggested the diagnosis ofjuvenile idiopathic Parkinson's disease (PD), but were followed by memory disturbance 1 year later. He showed parkinsonism, dementia, personality change, fluctuating cognition and visual hallucinations 3 years later. Neuroradiological examination revealed moderate brain atrophy, predominantly in the frontal and temporal lobes. Neuropathological examination demonstrated a widespread occurrence of lewy bodies (LB) with LB-related neurites not only in the brainstem but also in the cerebrum. The present case showed Lewy pathology which corresponded to stage IV by our staging and was parallel to neuronal loss. There was marked neuronal loss with many LB-related neurites in the CA2 of the hippocampus. neurofibrillary tangles (NFT) were almost restricted to the entorhinal cortex, while senile plaques were absent. Consequently, the present case was pathologically diagnosed as having DLB of the neocortical type, pure form. In the present study, we suggest that Lewy pathology in the cerebral cortex could be responsible for progressive dementia.- - - - - - - - - - ranking = 1.4231374673241keywords = brain, atrophy (Clic here for more details about this article) |
10/29. Idiopathic rapid eye movement sleep behavior disorder is a harbinger of dementia with lewy bodies.Idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia clinically linked with the alpha-synucleinopathies multiple systems atrophy (MSA), Parkinson's disease (PD), and dementia with lewy bodies (DLB). Available autopsy information is limited but suggests that the pathologic basis of idiopathic RBD may be neuronal loss and lewy bodies in pigmented monoaminergic nuclei, including the locus coeruleus and substantia nigra, which project to pontine nuclei mediating atonia during REM sleep. Thus, idiopathic RBD may be an alpha-synucleinopathy per se and a harbinger of impending PD, DLB, or MSA. Inclusion of historical or concurrent idiopathic RBD in the diagnostic criteria for DLB may improve their sensitivity, specificity, and clinical utility.- - - - - - - - - - ranking = 0.42313746732415keywords = atrophy (Clic here for more details about this article) |
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