Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myoclonus is a clinical symptom (or sign) defined as sudden, brief, shock-like, involuntary movements caused by muscular contractions or inhibitions. It may be classified by examination findings, etiology, or physiological characteristics. The main physiological categories for myocolonus are cortical, cortical-subcortical, subcortical, segmental, and peripheral. Neurodegenerative syndromes are potential causes of symptomatic myoclonus. Such syndromes include multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, frontotemporal dementia and parkinsonism linked to chromosome 17, Huntington's disease, dentato-rubro-pallido-luysian atrophy, Alzheimer's disease, and Parkinson's disease, and other Lewy body disorders. Each neurodegenerative syndrome can have overlapping as well as distinctive clinical neurophysiological properties. However, claims of differentiating between neurodegenerative disorders by using the presence or absence of small amplitude distal action myclonus appear unwarranted. When the myoclonus is small and repetitive, it may not be possible to distinguish it from tremor by phenotypic appearance alone. In this case, clinical neurophysiological offers an opportunity to provide greater differentiation of the phenomenon. More study of the myoclonus in neurodegenerative disease will lead to a better understanding of the processes that cause phenotypic variability among these disorders.
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PMID:Myoclonus and neurodegenerative disease--what's in a name? 1261 52

Accumulation of reactive oxygen species (ROS), which is generated during energy metabolism, is a cause of physiological aging, neuropathogenesis and numerous diseases, such as Parkinson's and Alzheimer's diseases. Zitter rat is an autosomal recessive mutant, characterized by spongiform degeneration and hypomyelination in the brain, and the phenotype has been suggested to be involved in oxidative stress by the accumulation of ROS. To determine the relation between neurodegeneration of the zitter rat and Attractin (Atrn) gene expression, which was identified as a gene responsible for the zitter, we established fibroblast cells from the zitter rat (Fz) and the Wistar tremor control (WTC) rat (Fw), and transduced Fz cells with the Atrn gene (Fz/Atrn). In the Fz/Atrn cells, accumulation of ROS was repressed, and cell survival against oxidative stress was enhanced to the same level as in Fw cells. Interestingly, phosphorylation of ERK was significantly increased in Fz/Atrn cells by H(2)O(2) stimulus, similarly to Fw cells. Furthermore, activation of ERK was confirmed in the brains of WTC and zitter rats by Western blot analysis and immunohistochemistry. These observations suggested that lack of Atrn gene expression induced neurodegeneration by a decrease in active ERK through an intracellular signaling via oxidative stress.
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PMID:Pivotal role of attractin in cell survival under oxidative stress in the zitter rat brain with genetic spongiform encephalopathy. 1265 11

There has been an increase of interest in olfactory dysfunction since it was realised that anosmia was a common feature of idiopathic Parkinson's disease (PD) and Alzheimer-type dementia (AD). It is an intriguing possibility that the first sign of a disorder hitherto regarded as one of movement or cognition may be that of disturbed smell sense. In this review of PD, parkinsonian syndromes, essential tremor, AD, motor neurone disease (MND) and Huntington's chorea (HC) the following observations are made: 1). olfactory dysfunction is frequent and often severe in PD and AD; 2). normal smell identification in PD is rare and should prompt review of diagnosis unless the patient is female with tremor-dominant disease; 3). anosmia in suspected progressive supranuclear palsy and corticobasal degeneration is atypical and should likewise provoke diagnostic review; 4). hyposmia is an early feature of PD and AD and may precede motor and cognitive signs respectively; 5). subjects with anosmia and one ApoE-4 allele have an approximate 5-fold increased risk of later AD; 6). impaired smell sense is seen in some patients at 50% risk of parkinsonism; 7). smell testing in HC and MND where abnormality may be found, is not likely to be of clinical value; and 8). biopsy of olfactory nasal neurons shows non-specific changes in PD and AD and at present will not aid diagnosis.
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PMID:Olfaction in neurodegenerative disorder. 1267 41

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. This disease is mainly characterized by tremor, bradykinesia, rigidity and postural instability that results primarily from a loss of dopaminergic neurons of the nigrostriatal pathway. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is well known to damage the nigrostriatal dopaminergic pathway, as seen in Parkinson's disease. Recent evidence shows that glial-related response plays a key role in the MPTP neurotoxic process, and the blockade of glial activation may be a new therapeutic approach to treating Parkinson's disease. In view of these new insights, this article suggests that the overexpression of S100beta protein secreted by glial cells may be an exacerbating factor in the neurodegeneration of dopaminergic cells in MPTP-treated animals. (c) 2002 Prous Science. All rights reserved.
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PMID:Glial Cells as a Target for the Development of New Therapies for Treating Parkinson's Disease. 1267 99

Recent research has shown that while Lewy body dementia. (LBD) may be the second most common form of dementia, it is difficult to confirm the disease before autopsy. Patients with LBD share many clinical signs and symptoms with patients diagnosed with Alzheimer's disease (AD), making it difficult to differentiate between the two diseases in patients who are still living. Still, our purpose in this study was to determine any clinical features which may differentiate between autopsy-confirmed cases of AD and cases of LBD. We compared 13 patients with autopsy-confirmed AD with 12 patients who had autopsy-confirmed LBD. Phone calls were made to family members of the deceased to help clarify and add any other information not documented in the patient's files. Significant differences were found in three areas, and trends approaching statistical significance were found in two other areas. Visual hallucinations were more prominent in the patients with LBD than in the patients with AD (10/12 LBD vs. 4/13 AD, P < 0.05). A nonspecific tremor was also found more often in the LB patients than in the Alzheimer's patients (8/12 LBD vs. 3/13 AD, P < 0.05). Finally, the LB patients were more prone to wandering, especially earlier in the disease course than were the patients with AD (10/12 LBD vs. 6/13 AD, P < 0.5). There was also a trend within the LB patients for higher use of anxiolytics (9/12 LBD vs. 6/13 AD, P = 0.14) as well as antidepressants (7/12 LBD vs. 4/13 AD, P = 0.16). Our data confirmed our hypothesis that LBD from a clinical perspective is indeed similar to AD. However, the higher incidence of visual hallucinations, tremor and wandering as well as the trend toward the use of anxiolytics and antidepressants among LB patients was noted. This gives hope that a clinical differentiation between these two diseases and more specific treatments may be possible in the future.
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PMID:Differentiating between lewy body dementia and Alzheimer's disease: a retrospective brain bank study. 1281 70

To study the incidence and topographic distribution of alpha-synuclein-positive inclusions in Parkinson's disease (PD), dementia with LB (DLB), and Alzheimer's disease (AD), 206 brains of elderly patients, including 53 patients with clinical PD, 110 autopsy-proven AD cases, 22 with dementia with LB (DLB), 1 case with essential tremor, and 20 age-matched controls were investigated using alpha-synuclein immunohistochemistry. For technical reasons, the olfactory system was not studied. In all PD brains, alpha-synuclein-positive inclusions and neuronal losses were present in medullary and pontine nuclei, locus coeruleus, and substantia nigra, with additional lesions in amygdala (24%), allocortex (58%), cingulate area (34%), and isocortex (26.5%). All PD cases corresponded to pathology stage 4-6 suggested by Braak et al. (2003, Neurobiol Aging 24:197). In most cases of DLB, the distribution of alpha-synuclein pathology and neurodegeneration corresponded to stages 5 and 6 of PD pathology. The case with essential tremor and 48.2% of the AD cases showed no LB pathology; in the other AD brains alpha-synuclein-positive inclusions were seen in various brain areas. None of the controls showed LB pathology. Among 12 cases of incidental Lewy body disease (without clinical parkinsonian signs), 7 corresponded morphologically to PD stage 3 or 4. In further 6 AD cases, 2 with parkinsonian symptoms, considerable damage to locus coeruleus, substantia nigra, nucleus basalis and allocortex with preservation of the medullary nuclei was seen. The preliminary data largely confirm the Braak staging of brain pathology, although some of the clinical PD cases corresponded to stage 3 often considered as "preclinical". In addition, some cases without demonstrable involvement of medullary nuclei showed extensive PD-like pathology in other brain areas, suggesting deviation from the proposed stereotypic expansion pattern and that incidental LB pathology may affect solely the locus coeruleus and substantia nigra. Striking similarity of LB pathology between DLB and PD suggests close morphological relationship between both disorders. Widespread LB lesions occurred in many sporadic AD cases without parkinsonian symptoms, the pathogenesis and clinical impact of which are unclear. The relationship between AD and PD with particular reference to alpha-synuclein-positive lesions needs further elucidation [corrected].
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PMID:Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study. 1284 52

Parkinson's disease (PD) is primarily a disease of elderly individuals with a peak age at onset of 55 to 66 years. It is characterized by bradykinesia, rigidity, tremor, and postural instability; and affects approximately 1 million individuals in the US and is the second most common neurodegenerative disease next to Alzheimer's disease. The motor symptoms of PD are the focus of pharmacotherapy, yet the nonmotor symptoms (e.g., dementia, psychosis, anxiety, insomnia, autonomic dysfunction, and mood disturbances) can be the most disturbing, disabling, and misunderstood aspects of the disease. Depressive symptoms occur in approximately half of PD patients and are a significant cause of functional impairment for PD patients. There is accumulating evidence suggesting that depression in PD is secondary to the underlying neuroanatomical degeneration, rather than simply a reaction to the psychosocial stress and disability. The incidence of depression is correlated with changes in central serotonergic function and neurodegeneration of specific cortical and subcortical pathways. Understanding comorbid depression in PD may therefore add to the understanding of the neuroanatomical basis of melancholia.
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PMID:Prevalence, etiology, and treatment of depression in Parkinson's disease. 1289 11

Functional imaging of the dopamine transporter (DAT) defines integrity of the dopaminergic system and has its main clinical application in patients with mild, incomplete, or uncertain parkinsonism. Imaging with specific single positron emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT) provides a marker for presynaptic neuronal degeneration. Striatal uptake correlates with disease severity, in particular bradykinesia and rigidity, and monitoring of progression assists in clinical trials of potential neuroprotective drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy and does not distinguish between these disorders. Dopamine loss is seen even in the earliest clinical presentations of true parkinsonism; a normal scan suggests an alternative diagnosis such as essential tremor, vascular parkinsonism (unless there is focal basal ganglia infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence between working clinical diagnosis and DAT imaging increases over time in favour of baseline DAT imaging results. Additional applications are characterising dementia with parkinsonian features (abnormal results in dementia with Lewy bodies, normal in Alzheimer's disease); and differentiating juvenile-onset Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).
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PMID:Role of dopamine transporter imaging in routine clinical practice. 1546

Parkinson's disease is a common neurodegenerative disorder primarily characterized by rigidity, tremor and bradykinesia. Cognitive impairment and neuropsychiatric symptoms are frequent in Parkinson's disease, with a 70% cumulative incidence of dementia. The aim of this cross-sectional study was to establish the pattern of cerebral atrophy on MRI in Parkinson's disease patients with dementia. We used voxel-based morphometry (VBM) to provide an unbiased means of investigating brain volume loss. Whole brain structural T1-weighted MRI scans from Parkinson's disease patients with dementia (PDD, n = 26), Parkinson's disease patients without dementia (n = 31), Alzheimer's disease patients (n = 28), patients with dementia with Lewy bodies (DLB, n = 17) and control subjects (n = 36) were acquired. Images were analysed using SPM99 and the optimized method of VBM. Reduced grey matter volume in PDD patients compared with controls was observed bilaterally in the temporal lobe, including the hippocampus and parahippocampal gyrus, and in the occipital lobe, the right frontal lobe and the left parietal lobe, as well as some subcortical regions. Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects. There was significant grey matter atrophy bilaterally in the occipital lobe of PDD patients compared with Parkinson's disease patients. In addition, significant temporal lobe atrophy, including the hippocampus and parahippocampal gyrus was detected in Alzheimer's disease relative to PDD. No significant volumetric differences were observed in PDD compared with DLB. Thus, Parkinson's disease involves grey matter loss in frontal areas. In PDD, this extends to temporal, occipital and subcortical areas, with occipital atrophy in PDD being the only difference between the two groups. This provides important information about the pattern of cerebral atrophy in Parkinson's disease and PDD.
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PMID:Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. 1474 92

Cholinesterase inhibitors vary in their selectivity for acetylcholinesterase versus butyrylcholinesterase. We examined several cholinesterase inhibitors and assessed the relative role of acetylcholinesterase versus butyrylcholinesterase inhibition in central and peripheral responses to these medications. Donepezil and icopezil are highly selective for acetylcholinesterase, whereas tacrine and heptylphysostigmine demonstrated greater potency for butyrylcholinesterase over acetylcholinesterase. All four compounds increased acetylcholine levels in mouse brains. Dose-response curves for tremor (central effect) and salivation (peripheral effect) showed that donepezil and icopezil possess a more favourable therapeutic index than the nonselective inhibitors, tacrine and heptylphysostigmine. Co-administration of the selective butyrylcholinesterase inhibitor tetraisopropylpyrophosphoramide (iso-OMPA) potentiated peripheral, but not central, effects of the selective acetylcholinesterase inhibitor icopezil. The improved therapeutic index observed in mice with icopezil is due to a high degree of selectivity for acetylcholinesterase versus butyrylcholinesterase, suggesting that high selectivity for acetylcholinesterase may contribute to the clinically favourable tolerability profile of agents such as donepezil in Alzheimer's disease patients.
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PMID:Pharmacology of selective acetylcholinesterase inhibitors: implications for use in Alzheimer's disease. 1475 2


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