Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003635 (apraxia)
 2,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rett syndrome (RS), which affects approximately 1 in 10,000 young females, is characterized by cognitive deterioration, ataxia, apraxia, rigidity, and stereotyped hand movements. Neuropathological features include reduction in brain size and hypopigmentation of neurons of the substantia nigra pars compacta (SNpc). Neurochemical and imaging studies support nigrostriatal involvement. The results of our preliminary studies show abnormalities in neurons of the substantia nigra (SN), including decreased numbers of neurons, ubiquitin-stained neuronal inclusion bodies, decreased immunostaining for transmitter markers, and evidence of cell death using terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end labeling (TUNEL), which labels fragmented intranucleosomal DNA. These preliminary data represent the first evidence for cell death in RS.
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PMID:Preliminary evidence for neurodegenerative changes in the substantia nigra of Rett syndrome. 756 48

We describe a clinico-pathological variant of a degenerative disorder involving Broca's, Wernicke's, and supplementary motor areas, which presented as primary progressive aphasia, dysarthria, bucco-facial apraxia, and hearing loss as initial symptoms, followed by organic personality changes. Postmortem examination revealed severe focal atrophy of the cerebral convolutions in the frontal operculum, superior frontal gyrus, and superior and transverse temporal gyri in addition to diffuse atrophy of the frontal and temporal lobes in both hemispheres. Microscopical examination revealed argyrophilic neuronal inclusions (ANIs) in the neuronal perikarya and presynaptic terminal throughout the central nervous system, as well as neuronal loss and swollen chromatolytic neurons in the affected cortices. Neocortical ANIs showed a positive immunoreaction with an anti-tau antibody but only a weak reaction with an anti-ubiquitin antibody immunohistochemically. Ultrastructurally, neocortical ANIs consisted of 15-nm thick smooth-surfaced tubules and tubules with constrictions at 120-150-nm intervals; thus they were different from the typical paired helical filaments of the 80-nm interval constrictions observed in the subiculum. ANIs were also found in the basal ganglia, brain stem nuclei, and cervical cord. Accordingly, ANIs appear distinct from neurofibrillary tangles (NFTs) of progressive supranuclear palsy, NFTs of Alzheimer-type dementia, and Pick bodies. The authors consider that this case fits the histopathological criteria of corticonigral degeneration with neuronal achromasia except for the unusual extension to the temporal lobes.
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PMID:Corticonigral degeneration with neuronal achromasia presenting with primary progressive aphasia: ultrastructural and immunocytochemical studies. 770 78

The group of Frontotemporal dementias (FTD) is composed of non-Alzheimer forms of dementia characterized clinically by behavioural and personality change leading to apathy and mutism. The disorder is associated with a progressive atrophy of the frontal, anterior temporal and anterior parietal lobes of the brain with several types of underlying pathology. One type (frontal lobe degeneration) is characterized by a microvacuolar degeneration of the outer cortical laminae along with a mild and mainly subpial gliosis and a loss of nerve cells, mostly from layers II and III. Another type shows transcortical tissue cavitation and florid gliosis with neuronal degeneration characterized by the presence of tau and ubiquitin positive inclusion bodies and alpha beta-crystallin-positive ballooned neurones: such changes have been termed 'Pick-type histology', and form the basis for the modern definition of 'Pick's disease'. The aetiological relationship between these two histological types is presently unknown. Both histologies can be differently distributed topographically throughout the brain to produce syndromes of progressive language disorder, when affecting bitemporal lobes or the left hemisphere preferentially, or progressive apraxia when parietal and motor regions are involved. Either pathology can be combined with or overlaps with that of classical motor neurone disease to produce motor neurone disease dementia. The underlying cause of FTD is unknown but genetic factors are strongly implicated. About half of cases show a previous family history of a similar disorder. In several families bearing a FTD clinical and pathological phenotype, linkage to chromosome 17 has been established but the pathology of this group appears distinctive and its relation to other forms of FTD awaits further elucidation. It is still possible that the many clinical and pathological variants of FTD may reflect different phenotypic expressions of a particular genetic change(s) at a single locus on this chromosome.
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PMID:Dementia of frontal type and dementias with subcortical gliosis. 954 90

The frontotemporal dementias are a group of relatively new and evolving clinical and pathologic entities. The predominant frontal-temporal atrophy causes a variety of clinical syndromes, usually dominated by disturbances in behavior, mood, and speech. The motor neuron disease-inclusion dementia (MNDID) subtype is characterized by the accumulation of specific intraneuronal ubiquitin-immunoreactive inclusions with the complete absence of tau immunoreactivity. We present a patient with the clinical and neuroimaging characteristics of a highly asymmetric neurodegenerative condition distinguished by limb rigidity, bradykinesia, dystonia with an alien limb phenomenon, cortical sensory findings, and limb apraxia. His premorbid diagnosis was cortical-basal ganglionic degeneration but he had the typical histologic features of a frontotemporal dementia of the MNDID subtype.
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PMID:Motor neuron disease-inclusion dementia presenting as cortical-basal ganglionic degeneration. 1043 7

Pathological examinations, using a panel of tau and other antibodies, were performed on the brains from 55 consecutively acquired cases of frontotemporal lobar degeneration (FTLD). Clinically, these comprised 31 cases of frontotemporal dementia (FTD), 10 cases of motor neurone disease inclusion dementia (MNDID), seven cases of progressive aphasia (PA), four cases of semantic dementia (SD) and three cases of progressive apraxia (PAX). Tau pathology, in the form of neurofibrillary tangles (NFTs) and glial cell tangles, was present in six cases of FTD with parkinsonism linked to chromosome 17, five of these cases resulting from +16 splice-site mutation and one from +13 mutation in the tau gene. The insoluble tau proteins were comprised mostly of four-repeat (4-R) isoforms. Eight other cases of FTD, one of PA and all three cases of PAX showed tau-positive inclusions (Pick bodies) and swollen cells (Pick cells), characteristic of Pick's disease. In these cases, the insoluble tau proteins were present in most instances as three-repeat (3-R) tau isoforms, although two cases with a mixture of 3-R and 4-R isoforms were seen. One other case of FTD showed an unusual pathology characterized by massive extracellular deposition of tau protein, composed of 4-R tau isoforms, within white matter without neuronal or glial cell inclusions. However, 33 (60%) of 55 FTLD cases showed no tau pathology in the brain, except for the rare NFTs, composed of a mix of 3-R and 4-R isoforms, in some of the more elderly cases. Of these 33 cases, 13 had FTD, 10 had MNDID, six had PA and four had SD. The pathological changes present were those of a superficial cortical laminar microvacuolation with mild subpial and subcortical gliosis; the 10 MNDID cases had ubiquitin-positive inclusions in the cerebral cortex and hippocampus. These 33 nontau FTLD cases, along with five Alzheimer's disease (AD) and six Huntington's disease (HD) cases with severe pathology, showed a variable loss of soluble tau proteins, broadly comparable with the extent of neuronal loss from the cortex and loss of the intracortical perikaryal marker, NeuN, but unrelated to proteins within afferent projection fibres such as neurofilament and alpha-synuclein. Levels of tau mRNA were decreased in parallel in the tau-negative FTLD cases and in the severe AD and HD cases. Hence, the loss of tau from these 33 nontau FTLD cases is just one aspect of a neurodegenerative process that destroys many components of the nerve cell machinery and does not represent a specific disordering of the cell's ability to form tau proteins or incorporate these into microtubules.
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PMID:The neuropathology of frontotemporal lobar degeneration with respect to the cytological and biochemical characteristics of tau protein. 1472 Jan 72

The term frontotemporal dementia (FTD) encompasses a range of clinical syndromes that are believed not to map reliably onto the spectrum of recognized pathologies. This study reexamines the relationships between clinical and pathological subtypes of FTD in a large series from two centers (n = 61). Clinical subtypes defined were behavioral variant FTD (n = 26), language variants (semantic dementia, n = 9; and progressive nonfluent aphasia, n = 8), and motor variants (corticobasal degeneration, n = 9; and motor neuron disease, n = 9), although most cases presented with a combination of behavioral and language problems. Unexpectedly, some behavioral cases (n = 5) had marked amnesia at presentation. The pathological subtypes were those with tau-immunopositive inclusions (with Pick bodies, n = 20; or without, n = 11), those with ubiquitin immunopositive inclusions (n = 16), and those lacking distinctive histology (n = 14). Behavioral symptoms and semantic dementia were associated with a range of pathologies. In contrast, other clinical phenotypes had relatively uniform underlying pathologies: motor neuron disease predicted ubiquitinated inclusions, parkinsonism and apraxia predicted corticobasal pathology, and nonfluent aphasia predicted Pick bodies. Therefore, the pathological substrate can be predicted in a significant proportion of FTD patients, which has important implications for studies targeting mechanistic treatments.
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PMID:Clinicopathological correlates in frontotemporal dementia. 1534 67

A 42-year-old, left-handed woman first noted impaired dexterity of the dominant hand, soon followed by dysarthria and cognitive decline. Over a 4-year period, she developed severe left-sided apraxia with eventual neglect of the left arm and progressive extrapyramidal signs. Cognitive testing showed progressive executive, visuospatial, fluency, and naming impairment with relative preservation of memory. Single-photon emission computed tomography demonstrated asymmetric right posterior frontal and superior parietal hypoperfusion. The clinical impression was corticobasal degeneration. At autopsy, severe atrophy was seen in the perirolandic and frontal regions. There was marked neuronal loss and gliosis in the posterior frontal and precentral regions and less severe pathology in prefrontal, temporal, and parietal areas. Mild to moderate gliosis and neuronal loss were also seen in the putamen, globus pallidus, subthalamic, and dentate nuclei. Gallyas silver stain revealed numerous inclusions adjacent to oligodendrocyte nuclei in white and gray matter of affected cortical and subcortical regions. The gracile inclusions were wavy, slender, and stained positively with antibodies to ubiquitin and alphaB-crystallin but not to microtubule-associated proteins (tau, MAP1B, MAP2), tubulin, neurofilaments, glial fibrillary acidic protein, or alpha-synuclein. The argyrophilic inclusions identified in this case are distinct from those previously described in neurodegenerative diseases.
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PMID:Corticobasal syndrome with novel argyrophilic glial inclusions. 1572 37

We have investigated the pathological correlates of dementia in the brains from a consecutive series of 70 patients dying with a clinical diagnosis of frontotemporal lobar degeneration (FTLD). Clinical misdiagnosis rate was low with only 3 patients (4%) failing to show pathological changes consistent with this diagnosis; 1 patient had Alzheimer's disease and 2 had cerebrovascular disease (CVD). In the remaining 67 patients, the most common underlying histological cause was ubiquitin pathology with 24 (36%) cases so affected. In these, ubiquitin-positive inclusions were present in the cerebral cortex as small, rounded or crescent-shaped structures within the cytoplasm of neurones of layer II, together with coiled or curvilinear bodies within neurites, and in the hippocampus as small, solid and more spherical-shaped inclusion bodies within the cytoplasm of dentate gyrus granule cells. In one patient, "cat's eye" or "lentiform" intranuclear ubiquitin inclusions were also present. The second most common histological type was dementia lacking distinctive histology (DLDH), in which neither tau nor ubiquitin inclusions were present, with 16 cases (24%) being affected. Pick-type histology was seen in 14 cases (21%) and tau histological changes associated with frontotemporal dementia (FTD) linked to chromosome 17 (FTDP-17) were present in 11 cases (16%). One case (1%) showed an unusual tau pathology that could not be allocated to any of the other tau groups. Only 1 case (1%) had neuronal intermediate filament inclusion dementia. No cases with ubiquitinated, valosin-containing protein-immunoreactive intranuclear inclusion bodies of the type seen in inclusion body myopathy with Paget's disease of bone and frontotemporal dementia were seen. Clinicopathological correlation showed that any of these histological subtypes can be associated with FTD. However, for FTD with motor neurone disease (FTD+MND), semantic dementia or primary progressive aphasia (PA), the histological profile was either ubiquitin type or DLDH type; Pick-type histology was seen in only 1 case of PA. None of these latter three clinical subtypes was associated with a mutation in tau gene and FTDP-17 type of tau pathology. All cases of progressive apraxia were associated with Pick-type histology. Present data therefore indicate that, although ubiquitin pathology is the most common histological form associated with FTLD, this pathology is not tightly linked with, nor is pathologically diagnostic for, any particular clinical form of the disease, including FTD+MND.
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PMID:Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation. 1622 25

Frontotemporal dementia (FTD) is the second most frequent type of neurodegenerative dementias. Mutations in the progranulin gene (GRN, PGRN) were recently identified in FTDU-17, an FTD subtype characterized by ubiquitin-immunoreactive inclusions and linkage to chromosome 17q21. We looked for PGRN mutations in a large series of 210 FTD patients (52 familial, 158 sporadic) to accurately evaluate the frequency of PGRN mutations in both sporadic and familial FTD, and FTD with associated motoneuron disease (FTD-MND), as well as to study the clinical phenotype of patients with a PGRN mutation. We identified nine novel PGRN null mutations in 10 index patients. The relative frequency of PGRN null mutations in FTD was 4.8% (10/210) and 12.8% (5/39) in pure familial forms. Interestingly, 5/158 (3.2%) apparently sporadic FTD patients carried a PGRN mutation, suggesting the possibility of de novo mutations or incomplete penetrance. In contrast, none of the 43 patients with FTD-MND had PGRN mutations, supporting that FTDU-17 and FTD-MND are genetically distinct. The clinical phenotype of PGRN mutation carriers was particular because of the wide range in onset age and the frequent occurrence of early apraxia (50%), visual hallucinations (30%), and parkinsonism (30%) during the course of the disease. This study supports that PGRN null mutations represent a more frequent cause of FTD than MAPT mutations (4.8% vs. 2.9%) but are not responsible for FTD-MND. It also demonstrates that half of the patients with a PGRN mutation in our series had no apparent family history of dementia. Taking this into account, genetic testing should be now considered more systematically, even in patients without obvious familial history of FTD.
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PMID:Progranulin null mutations in both sporadic and familial frontotemporal dementia. 1743 89

Frontotemporal lobar degeneration (FTLD) encompasses a heterogeneous group of clinical syndromes that include frontotemporal dementia (FTD), frontotemporal dementia with motor neurone disease (FTD/MND), progressive non-fluent aphasia (PNFA), semantic dementia (SD) and progressive apraxia (PAX). Clinical phenotype is often assumed to be a poor predictor of underlying histopathology. Advances in immunohistochemistry provide the opportunity to re-examine this assumption. We classified pathological material from 79 FTLD brains, blind to clinical diagnosis, according to topography of brain atrophy and immunohistochemical characteristics. There were highly significant relationships to clinical syndrome. Atrophy was predominantly frontal and anterior temporal in FTD, frontal in FTD/MND, markedly asymmetric perisylvian in PNFA, asymmetric bitemporal in SD and premotor, parietal in PAX. Tau pathology was found in half of FTD and all PAX cases but in no FTD/MND or SD cases and only rarely in PNFA. FTD/MND, SD and PNFA cases were ubiquitin and TDP-43 positive. SD cases were associated with dystrophic neurites without neuronal cytoplasmic or intranuclear inclusions (FTLD-U, type 1), FTD/MND with numerous neuronal cytoplasmic inclusions (FTLD-U, type 2 ) and PNFA with neuronal cytoplasmic inclusions, dystrophic neurites and neuronal intranuclear inclusions (FTLD-U, type 3). MAPT mutations were linked to FTD and PGRN mutations to FTD and PNFA. The findings demonstrate predictable relationships between clinical phenotype and both topographical distribution of brain atrophy and immunohistochemical characteristics. The findings emphasise the importance of refined delineation of both clinical and pathological phenotype in furthering understanding of FTLD and its molecular substrate.
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PMID:Frontotemporal lobar degeneration: clinical and pathological relationships. 1756 65


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