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)

Parkinsonism plus syndrome is a group of heterogeneous degenerative neurological disorders, which differ from the classical idiopathic Parkinson's disease in certain associated clinical features, poor response to levodopa, distinctive pathological characteristics and poor prognosis. Associated clinical features include symmetrical onset, infrequent or atypical tremor, prominent rigidity in axial musculature, bradykinesia, early postural instability, supranuclear gaze palsy, early autonomic failure, pyramidal affection, cerebellar involvement, alien limb phenomenon, apraxia and significant early cognitive dysfunction in some cases. Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and dementia with Lewy body disease (DLB) are commoner disorders. Less frequent disorders are cortico-basal ganglionic degeneration (CBGD), frontotemporal dementia with chromosome 17 (FTDP-17), Pick's disease, parkinsonian-dementia complex of Guam, Pallidonigral degeneration, Wilson's disease and a rigid variant of Huntington's disease. During the last 3 decades, major progress has been made in understanding PSP, CBGD and FTDP-17, which are tau disorders. MSA and DLB together with idiopathic Parkinson's disease are called alpha-synucleinopathies. Recent studies show that the diagnosis of these Parkinsonism plus syndromes improves when strict diagnostic criteria are used. However, unusual presentations may pose a diagnostic challenge. The shortcomings of the current studies demand the need for further research to identify biologic markers that may allow earlier diagnosis, and understanding of the factors leading to alpha-synuclein or tau aggregation. Identification of therapeutic strategies that may prevent the aggregation of these proteins and rescue dysfunctional cells has been stressed. This review focuses on the advances in the clinical, neuroimaging, pathologic, genetic and management aspects of these disorders.
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PMID:Parkinsonism plus syndrome--a review. 1457 Sep 99

Parkinson's disease is associated with classical Parkinsonian features that respond to dopaminergic therapy. Neuropsychiatric sequelae include dementia, major depression, dysthymia, anxiety disorders, sleep disorders, and sexual disorders. Panic attacks are particularly common. With treatment, visual hallucinations, paranoid delusions, mania, or delirium may evolve. Psychosis is a key factor in nursing home placement, and depression is the most significant predictor of quality of life. Clozapine may be the safest treatment for psychotic features, but more research is needed to establish the efficacy of antidepressant treatments. Dementia with Lewy bodies, the second most common dementia in the elderly, may present in association with systematized delusions, depression, or RBD. Early evidence suggests the utility of rivastigmine, donepezil, low-dose olanzapine, and quetiapine in treating DLB. Parkinson-plus syndromes generally lack a good response to dopaminergic treatment and evidence additional features, including dysautonomia, cerebellar and pontine features, eye signs, and other movement disorders. MSA is associated with dysautonomia and RBD. SND (MSA-P) is associated with frontal cognitive impairments, but dementia, psychosis, and mood disorders have not been strikingly apparent unless additional pathological findings are present. In SDS (MSA-A), impotence is almost ubiquitous; urinary incontinence is frequent; depression is occasional, and sleep apnea should be treated to avoid sudden death during sleep. OPCA neuropsychiatric correlates await further definition. Progressive supranuclear palsy neuropsychiatric features include apathy, subcortical dementia, pathological emotionality, mild depression and anxiety, and lack of appreciable response to donepezil. CBD usually is recognized by early frontal dementia with ideomotor apraxia, often in the right upper extremity, attended later by poorly responsive unilateral Parkinsonism, with additional signs including cortical reflex myoclonus, limb dystonia, alien limb, oculomotor apraxia when asked to look horizontally, depression, personality changes, and, occasionally, Kluver-Bucy syndrome. The neuropsychiatry of FTDP-17 involves apraxia, executive impairment, personality changes, hyperorality, and occasional psychosis. Future research in these Parkinsonian disorders should target the characterization of neuropsychiatric sequelae and their treatment.
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PMID:The neuropsychiatry of Parkinson's disease and related disorders. 1555 Feb 93

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are both sporadic disorders with tau pathology. Criteria have been defined that in most instances allow for adequate diagnosis of the two disorders both clinically and neuropathologically; however, overlap is not uncommon. For example, patients with PSP may present with severe unilateral apraxia and supranuclear gaze palsy can occur in CBD. Pathological overlap also occurs and pathologically "mixed" cases are encountered. Common to both these two tauopathies is that isoforms of four-repeat tau due to splicing of exon 10 define the tau filamentous aggregates. This is in contrast to other tau disorders such as Pick's with three-repeat tau aggregates. Additional evidence for a causal link between PSP and CBD is the finding that both disorders are homozygous for the H1 tau haplotype. Furthermore, in some families with parkinsonism linked to defined mutations of the tau gene (FTDP-17), involved relatives have presented with PSP whereas others with the CBD phenotype. Although PSP and CBD frequently can be clearly separated clinically and pathologically, the degree of clinicopathological and genetic overlap is important and suggests that they represent different phenotypes of the same disorder, with differences occurring perhaps in relation to different genetic background. That PSP and CBD are distinct nosological entities occurring in patients with similar genetic predisposition cannot be ruled out.
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PMID:Progressive supranuclear palsy and corticobasal degeneration: lumping versus splitting. 1609 76

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

We report a Japanese man with familial parkinsonism who died at age 54. His younger brother, his mother, the mother's 4 brothers, and their mother were also affected with similar parkinsonism. The patient had had nystagmus since adolescence. He noticed difficulty in walking and micrographia at age 42. Neurological examination at age 45 in our hospital revealed pendular nystagmus, moderate rigidity in his neck and upper limbs, postural tremor in hands and shuffling gait. He received L-dopa/benzerazide 200 mg and his movement was mildly improved. Then he developed forced closing of eyelids suggesting either blepharospasms or apraxia of eye lid opening. He became apathetic at age 48. He was admitted to our hospital at age 49. On admission, he showed mild dementia and sexually disinhibited behaviours. Moderate downward gaze palsy and rigidity were seen. Increase of L-dopa/benzerazide and pergolide did not improve his parkinsonism and his disinhibited behaviors became worse. L-dopa/benzerazide and pergolide were decreased and he received electroconvulsive therapy at a psychiatric hospital with temporally improvement in his movement. He became unable to walk at age 52 and he was mutic and bedridden. He died of pneumonia at age 54. The patient was discussed in a neurological CPC, and a chief discussant arrived at the conclusion that the patient had a familial form of dementia with Lewy bodies. Many participants thought that he had frontotemporal dementia and parkinsonism linked to chromosome 17. The pathological examination of his brain showed severe neuronal loss in the substantia nigra, subthalamus, and pallidum. Ballooned neurons were observed in the cerebral cortex. Immunohistochemistry using anti-tau antibodies revealed tau-positive neurons, glial cells and threads in the cerebral cortex, white matter and subcortical nuclei; these tau deposition reacted with an anti-4-repeat tau antibody, but not reacted to an anti-3-repeat tau antibody. Sequencing of genomic DNA of the patient showed a missense mutation in exon 10 of tau that caused a substitution at codon N279K. These neuropathological and molecular studies revealed the diagnosis of the patient was FTDP-17 with N279K mutation.
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PMID:[A 54-year-old man with familial parkinsonism, gaze palsy, and dementia]. 1637 98