Cases reported "Dementia"

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1/56. Clinical genetics of familial progressive supranuclear palsy.

    Recent studies have shown that progressive supranuclear palsy (PSP) could be inherited, but the pattern of inheritance and the spectrum of the clinical findings in relatives are unknown. We here report 12 pedigrees, confirmed by pathology in four probands, with familial PSP. Pathological diagnosis was confirmed according to recently reported internationally agreed criteria. The spectrum of the clinical phenotypes in these families was variable including 34 typical cases of PSP (12 probands plus 22 secondary cases), three patients with postural tremor, three with dementia, one with parkinsonism, two with tremor, dystonia, gaze palsy and tics, and one with gait disturbance. The presence of affected members in at least two generations in eight of the families and the absence of consanguinity suggests autosomal dominant transmission with incomplete penetrance. We conclude that hereditary PSP is more frequent than previously thought and that the scarcity of familial cases may be related to a lack of recognition of the variable phenotypic expression of the disease.
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ranking = 1
keywords = progressive supranuclear, supranuclear, supranuclear palsy, palsy
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2/56. A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy.

    Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia. The proband died severely demented 7 years after the onset of the symptoms; currently, his brother is still alive although his disease is progressing. In both patients, we found a Tau gene mutation in exon 10 at codon 279, resulting in an asparagine to lysine substitution (N279K). Neuropathologically, widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brain stem nuclei as well as in the white matter were the hallmark of the disease. These deposits were shown by immunohistochemistry and immunoelectron microscopy, using a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes present in multiple tau regions. In the neocortex, tau-immunopositive glial cells were more numerous than immunopositive neurons; the deeper cortical layers as well as the white matter adjacent to the cortex contained the largest amount of immunolabeled glial cells. In contrast, some brain stem nuclei contained more neurons with tau deposits than immunolabeled glial cells. The correlation of clinical, neuropathological and molecular genetic findings emphasize the phenotypic heterogeneity of diseases caused by Tau gene mutations. Furthermore, to test the effect of the N279K mutation and compare it with the effect of the P301L exon 10 mutation on alternative splicing of Tau exon 10, we used an exon amplification assay. Our results suggest that the N279K mutation affects splicing similar to the intronic mutations, allowing exon 10 to be incorporated more frequently in the Tau transcript.
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ranking = 0.46138060487243
keywords = supranuclear, supranuclear palsy, palsy
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3/56. Parkinsonism, dementia and vertical gaze palsy in a Guamanian with atypical neuroglial degeneration.

    A 58-year-old Chamorro female patient, who died in 1993, was examined clinicopathologically. At the age of 51, she suffered from hemiparkinsonism, then bradykinesia, rigidity without tremor, and dementia. Extrapyramidal symptoms developed, and at the age of 57, vertical gaze palsy was noted. The clinical diagnosis was parkinsonism-dementia complex (PDC) with vertical gaze palsy. The brain showed atrophy in the frontal and temporal lobes, and the atrophy was accentuated in the dentate gyrus, Ammon's horn and parahippocampal gyrus. The basal ganglia, thalamus and midbrain were moderately atrophic. The substantia nigra and locus ceruleus were completely depigmented. Numerous neurofibrillary tangles (NFTs) were seen in the subiculum and amygdaloid nucleus. Many NFTs were evident in the parahippocampal gyrus, lateral occipitotemporal gyrus, insula, Sommer sector, basal nucleus of meynert, lateral nucleus of the thalamus, subthalamic nucleus and brain stem, and several were observed in the globus pallidus and hypothalamus. The Sommer sector, substantia nigra, locus ceruleus and basal nucleus of meynert showed severe loss of neurons, and a moderate loss of neurons was exhibited by the globus pallidus. These findings were apparently consistent with those associated with PDC. However, in this patient, severe neuronal loss was seen in the subthalamic nucleus and lateral nucleus of the thalamus, and grumose degeneration, which has not previously been reported in PDC, was seen in the dentate nucleus. In addition, many tufted astrocytes, which have been reported to occur in progressive supranuclear palsy (PSP) and postencephalitic parkinsonism, but scarcely observed in PDC, were present. Furthermore, astrocytic plaques, which have been considered as a specific finding of corticobasal degeneration (CBD), were observed in the cerebral cortex. On the other hand, granular hazy astrocytic inclusions, previously reported to occur in PDC, were not seen. Chromatolytic neurons were not observed. The question thus arises as to whether it is appropriate to consider this patient as having suffered from a combination of PDC, PSP and CBD. From the view points of absence of granular hazy astrocytic inclusions and chromatolytic neurons, and of tufted astrocytes in the neostriatum, it is conceivable that this patient is a case of a new disease entity.
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ranking = 0.20005082839103
keywords = progressive supranuclear, supranuclear, supranuclear palsy, palsy
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4/56. Single-fiber PCR in MELAS(3243) patients: correlations between intratissue distribution and phenotypic expression of the mtDNA(A3243G) genotype.

    We performed morphological, biochemical, and genetic studies, including single-fiber PCR (sf PCR), on muscle biopsies obtained from a mother and daughter with melas syndrome due to the A3243G transition of mitochondrial dna (mtDNA). The severity of muscle involvement appeared quite distinct, in spite of the fact that both patients segregated similar mutant mtDNA levels on total muscle dna. The daughter did not show any clinical muscle involvement: muscle biopsy revealed many ragged red fibers (RRFs) mostly positive for cytochrome-c oxidase (COX) activity. In contrast, her mother had developed a generalized myopathy without progressive external ophthalmoplegia (PEO), morphologically characterized by many COX-negative RRFs. Single-muscle fiber PCR demonstrated in both patients significantly higher percentages of wild-type mtDNA in normal fibers (daughter: 23.25 /- 15.22; mother: 43.13 /- 26.11) than in COX-positive RRFs (daughter: 11.25 /- 5.22, P < 0.005; mother: 9.12 /- 5.9, P < 0.001) and in COX-negative RRFs (daughter: 8.9 /- 4.2, P < 0.001 mother: 4.8 /- 2.8, P < 0.001). Wild-type mtDNA levels resulted higher also in COX-positive vs. COX-negative RRFs (daughter: P < 0.05; mother: P < 0.001). Our data confirm a direct correlation between A3243G levels and impairment of COX function at the single-muscle fiber level. Moreover, the evidence of a clinical myopathy in the patient with higher amounts of COX-negative RRFs bolsters the concept that a differential distribution of mutant mtDNAs at the cellular level may have effects on the clinical involvement of individual tissues. However, the occurrence of a similar morphological and biochemical muscle phenotype also in PEO(3243) patients suggests that other genetic factors involved in the interaction between mitochondrial and nuclear dna, rather than the stochastic distribution of mtDNA genomes during embryogenesis, are primarily implicated in determining the various clinical expressions of the A3243G of mtDNA.
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ranking = 0.00020684411323499
keywords = ophthalmoplegia
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5/56. July 2000: A 70 year old with rigidity, decreased ocular movements, and dementia.

    The July Case of the Month (COM): A 70 year old male presented with a four year history of cognitive decline, difficulty expressing himself, and an increasingly unsteady gait with numerous falls. At presentation he was wheel-chair bound. Examination showed some slowing of speech, mild memory impairment, but normal cranial nerves. Spastic weakness and brisk reflexes were also noted, with bilateral ankle clonus. MRI scans were normal. Four years later he was admitted with a urinary tract infection and was mute with severely impaired ocular motility. He died 18 months later and autopsy showed the classic neuropathological findings of typical Progressive supranuclear palsy, including tau-positive glial inclusions.
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ranking = 0.080057538867162
keywords = supranuclear, supranuclear palsy, palsy
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6/56. A case of frontotemporal dementia and parkinsonism of early onset with progressive supranuclear palsy-like features.

    We report a patient with frontotemporal degeneration and parkinsonism with mental retardation. The patient was a 54-year-old man who had parkinsonism that resembled progressive supranuclear palsy, frontotemporal degeneration and myoclonus. His family included many affected members. Neuropathologically, there was degeneration of the frontal and temporal cortices, the basal ganglia, the brainstem and the cerebellum. Microscopically, neuronal loss was severe in the frontal and temporal cortex, the globus pallidus, substantia nigra, red nucleus and dentate nucleus. Fibrillary changes were found in neurons and glia that were immunostained for tau. Although we could not define the genetic abnormalities, we thought that this case might have involved frontotemporal dementia and parkinsonism linked to chromosome 17.
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ranking = 0.99999123648431
keywords = progressive supranuclear, supranuclear, supranuclear palsy, palsy
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7/56. frontal lobe dementia with novel tauopathy: sporadic multiple system tauopathy with dementia.

    We present a novel tauopathy in a patient with a 10-yr history of progressive frontal lobe dementia and a negative family history. autopsy revealed mild atrophy of frontal and parietal lobes and severe atrophy of the temporal lobes. There were occasional filamentous tau-positive inclusions, but more interesting were numerous distinctive globular neuronal and glial tau-positive inclusions in both gray and white matter of the neocortex. Affected subcortical regions included substantia nigra, globus pallidus, subthalamic nucleus, and cerebellar dentate nucleus, in a distribution similar to progressive supranuclear palsy (PSP), but without significant accompanying neuronal loss or gliosis. Predominantly straight filaments were detected by electron microscopy (EM), while other inclusions were similar to fingerprint bodies. No twisted ribbons were detected. Immuno-EM studies revealed that only the filamentous inclusions were composed of tau. immunoblotting of sarkosyl-insoluble tau revealed 2 major bands of 64 and 68 kDa. Blotting analysis after dephosphorylation revealed predominantly 4-repeat tau. sequence analysis of tau revealed that there were no mutations in either exons 9-13 or the adjacent intronic sequences. The unique cortical tau pathology in this case of sporadic multiple system tauopathy with dementia adds a new pathologic profile to the spectrum of tauopathies.
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ranking = 0.19999824729686
keywords = progressive supranuclear, supranuclear, supranuclear palsy, palsy
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8/56. frontotemporal dementia with ubiquitinated cytoplasmic and intranuclear inclusions.

    Dementia of motor neuron disease type (DMND) is a variety of frontotemporal dementia (FTD) which is pathologically defined by characteristic neuronal ubiquitinated, tau- and synuclein-negative intracytoplasmic inclusions. Many cases with this pathology, however, do not have motor neuron disease. In the present study, we document the presence of ubiquitinated neuronal intranuclear inclusions in a sub-population of cases of neuropathologically verified DMND. Immunohistochemical localization of ubiquitin was performed on sections of post-mortem brain from 12 patients with DMND as well as from cases with other neurodegenerative diseases including amyotrophic lateral sclerosis, Parkinson's disease, dementia with lewy bodies, corticobasal degeneration, progressive supranuclear palsy, and multiple system atrophy. All of the cases of DMND showed ubiquitinated, tau-negative intracytoplasmic inclusions in dentate granule cells and cortical neurons. Of these 12 cases of DMND, 3 also showed neuronal ubiquitinated intranuclear inclusions. In 1 of these cases, CAG repeat expansions in the genes known to harbor these mutations were excluded. Cases with intranuclear inclusions displayed striatal atrophy and reduced brain weight relative to non-inclusion-bearing cases. In addition, patients with intranuclear inclusions tended to have a younger age of onset, a prolonged duration of disease, absence of motor neuron symptoms, and a family history of dementia. Intranuclear inclusions were not identified in the control cases with other neurodegenerative diseases. Ubiquitinated neuronal intranuclear inclusions have not been reported previously in DMND. The presence of ubiquitinated intranuclear inclusions along with striatal atrophy in a subset of cases of DMND may signify the existence of a neuropathologically distinct subset of this unique form of FTD.
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ranking = 0.19999824729686
keywords = progressive supranuclear, supranuclear, supranuclear palsy, palsy
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9/56. machado-joseph disease with retinal degeneration and dementia.

    OBJECTIVES: To clarify the phenotypic varieties in machado-joseph disease (MJD). MATERIALS AND methods: We studied a 64-year-old man with ataxia, retinal degeneration and dementia neurologically, ophthalmologically and genetically. RESULTS: The patient noted dysesthesia of his hands at age 57 and later had memory disturbance. He had gait disturbance and needed a wheelchair at age 64. His total IQ was 61 on the WAIS-R. He had loss of central vision, ophthalmoplegia, hearing impairment, dysarthria, truncal and limb ataxia, sensory disturbance, and mild weakness of the extremities. Electrophysiologically he was suspected to have polyneuropathy. Brain MRI showed marked atrophy of the cerebellum and pons with mild cerebral atrophy. Ophthalmologic evaluation revealed multiple chorioretinal atrophy. Expanded CAG repeat numbers in MJD1 were 64. CONCLUSION: These findings indicate that the clinical features of MJD might cover a wider spectrum than previously expected, though it is possible that these complications, namely retinal degeneration and dementia, were incidental findings in this patient.
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ranking = 0.00020684411323499
keywords = ophthalmoplegia
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10/56. Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation.

    We report a case of frontotemporal dementia and parkinsonism linked to chromosome 17 of 5 years' duration in an 81-year-old man whose brother had died at age 86 years with dementia. In this patient, we found frontal and temporal neuronal loss, glial-predominant tau deposits, progressive supranuclear palsy-like straight tubules, accumulation of 4-repeat-predominant Sarkosyl-insoluble tau, and a novel exon 1 (Arg5His) tau gene mutation. This mutation decreased microtubule-promoting capacity and increased fibrillation of tau in vitro. Thus, we consider that the Arg5His mutation is an authentic tau gene abnormality responsible for the patient's tau pathology and late-onset dementia.
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ranking = 0.19999824729686
keywords = progressive supranuclear, supranuclear, supranuclear palsy, palsy
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