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Parkinsonian Signs (parkinsonian + sign)

Distribution by Scientific Domains

Medical Sciences	85%

Selected Abstracts

Mild Parkinsonian signs: An overview of an emerging concept

MOVEMENT DISORDERS, Issue 12 2007
Elan D. Louis MD
Abstract Mild Parkinsonian signs (MPS) include gait and balance changes, rigidity, bradykinesia, and tremor. MPS can occur commonly during the clinical examination of older people who do not have known neurological disease, with prevalence estimates for MPS as a whole ranging from 15% to 95%. MPS are generally progressive and they are coupled with functional difficulties, impaired gait and balance, and increased risks of mild cognitive impairment, dementia, and mortality. The mechanistic basis for these signs is unclear, but is likely to be multifactorial, with possible factors including an age-associated decline in dopaminergic nigrostriatal activity, the early development of neurodegenerative (Lewy body or Alzheimer's type) pathologies in the basal ganglia, or the accumulation of vascular pathology in the brain. It would be valuable to identify those individuals with MPS who are at increased risk for the development of future Alzheimer's disease, full-blown Parkinson's disease, or strokes, and to develop therapeutic strategies to intervene to lessen the likelihood of MPS-related morbidity and mortality. © 2007 Movement Disorder Society [source]

Parkinsonian signs and substantia nigra neuron density in decendents elders without PD,

ANNALS OF NEUROLOGY, Issue 4 2004
G. Webster Ross MD
Substantia nigra (SN) neurons were counted on single, transverse caudal midbrain sections from 217 male participants in the Honolulu-Asia Aging Study, aged 74,97 years at death. Quadrants areas within the SN were determined with a planimeter and neuronal density was expressed as neurons/mm2 for 10 Parkinson's disease (PD) cases, 29 incidental Lewy body cases, and 178 controls with neither condition. Mean densities in all quadrants were significantly lower in the PD group compared with the other groups (p = 0.006). This relationship was strongest in the ventrolateral quadrant. In a subgroup of 50 controls who were examined with the Unified Parkinson's Disease Rating Scale an average of 2.1 years prior to death, there was an association of stooped posture (p = 0.009), postural instability (p = 0.013), body bradykinesia (p = 0.048), and gait disturbance (p = 0.05) with neuron density in the dorsolateral quadrant; and impaired speech (p = 0.014), abnormal facial expression (p = 0.022), and difficulty rising from a chair (p = 0.032) with neuron density in the dorsomedial quadrant. There was a significant association of increasing number of signs present with decreasing neuron density in both quadrants (p = 0.001 for trend). Low SN neuron density may be the basis for parkinsonian signs in the elderly without PD. Ann Neurol 2004 [source]

Pre-clinical studies of pramipexole: clinical relevance

EUROPEAN JOURNAL OF NEUROLOGY, Issue 2000
J. P. Hubble
This paper reviews the preclinical study of the novel dopamine agonist pramipexole and its use in early Parkinson's disease (PD). Emphasis will be given to those properties distinguishing this drug from other dopamine agonists, the relevance of the preclinical data to clinical trial results in early PD, and the putative neuroprotective properties of the compound. The conventional dopamine agonists are ergot-derived compounds that are most widely used as adjunctive therapies in advancing Parkinson's disease (PD). Examples of conventional agonists are bromocriptine and pergolide. Pramipexole is an aminobenzothiazole compound, recently introduced for the treatment of both early and advanced PD. Its nonergot structure may reduce the risk of side-effects, considered unique to ergot drugs, such as membranous fibrosis. Pramipexole is a full dopamine agonist with high selectivity for the D2 dopamine receptor family. This family includes the D2, D3 and D4 receptor subtypes. Pramipexole has a 5- to 7-fold greater affinity for the D3 receptor subtype with lower affinities for the D2 and D4 receptor subtypes. The drug has only minimal ,2 -adrenoceptor activity and virtually no other receptor agonism or antagonism. The optimal dopamine receptor activation for the safe and effective treatment of PD is not known. Findings in animal models and clinical studies indicate that activation of the postsynaptic D2 receptor subtype provides the most robust symptomatic improvement in PD. Given its pharmacological profile, it is not surprising that pramipexole was found to be effective in ameliorating parkinsonian signs in animal models. This therapeutic effect has been confirmed in clinical trials in both early and advanced PD. In early disease, it provides a clear reduction in the chief motor manifestations of PD and improved activities of daily living. Perhaps most striking is the large number of clinical trial patients who have remained on pramipexole monotherapy for many months. The majority of these subjects have been maintained on pramipexole for an excess of 24 months without requiring additional symptomatic treatment with levodopa. This is in contrast to the general clinical experience with older conventional agonists. Pramipexole also has a favourable pharmacokinetic profile. It is rapidly absorbed with peak levels appearing in the bloodstream within 2 h of oral dosing. It has a high absolute bioavailability of > 90% and can be administered without regard to meals. It has no significant effects on other antiparkinson drugs such as levodopa or selegiline. Its excretion is primarily renal and, thus, has little or no impact on hepatic cytochrome P450 enzymes or other related metabolic pathways. Pramipexole has also been theorized to have ,neuroprotectant' properties. Oxyradical generation is posited as a cause or accelerant of brain nigral cell death in PD. Pramipexole stimulates brain dopamine autoreceptors and reduces dopamine synthesis and turnover which may minimize oxidative stress due to dopamine metabolism. Furthermore, the compound has a low oxidation potential that may serve as an oxyradical scavenger in the PD brain. In summary, pramipexole is a new antiparkinson medication found to have unique dopamine agonist characteristics and putative neuroprotective properties. [source]

Wide expressivity variation and high but no gender-related penetrance in two dopa-responsive dystonia families with a novel GCH-I mutation

MOVEMENT DISORDERS, Issue 10 2004
Antonino Uncini MD
Abstract We describe the clinical and molecular correlates in two Italian families with dopa-responsive dystonia (DRD) and the same novel mutation of GTP-cyclohydrolase I (GCH-I) gene. Thirty-five subjects were examined and the genotype correlated to phenotype. Childhood onset foot dystonia is present in 7 subjects currently under the age of 40. In 1 patient bilateral foot dystonia was evident at birth suggesting that dystonia may be active as early as in utero. In another patient, dystonia spontaneously remitted in adolescence, to relapse 8 years later, as writer's cramp. Dystonia and parkinsonian signs are present in 5 other patients. In 2 subjects an isolated parkinsonism started over the age of 45. A 5-base pair insertion at codon 242 within exon 6 of GTP-cyclohydrolase I (GCH-I) gene that shifts the reading frame and results in a premature stop at codon 247 with truncation of the polypeptide has been detected in 21 subjects. Considering dystonia and parkinsonism the overall penetrance is 0.71 and not significantly different in men (0.69) and women (0.75). Genealogical studies seem to exclude that these families are related but haplotype analysis suggests a single founder. Our findings in subjects with the same mutation indicate a wide intrafamilial variation in expressivity and high penetrance in DRD but do not confirm the reported influence of gender on GCH-I gene mutation penetrance. © 2004 Movement Disorder Society [source]

Parkinsonian signs and substantia nigra neuron density in decendents elders without PD,

Detrimental deletions: mitochondria, aging and Parkinson's disease

BIOESSAYS, Issue 10 2006
Saskia Biskup
As individuals enter their 80s, they are inevitably confronted with the problem of neuronal loss in the brain. The incidence of the common movement disorder ,mild parkinsonian signs' (MPS) is approximately 50% over the age of 85 years. It has long been known that the loss of dopaminergic neurons in the substantia nigra pars compacta is a neuropathological hallmark of Parkinson's disease (PD). Recently, two papers1,2 present clear evidence for a high burden of mitochondrial DNA deletions within substantia nigra neurons in aged individuals and individuals with PD, pointing towards a common pathway inevitably leading to neuronal dysfunction and death. BioEssays 28: 963,967, 2006. © 2006 Wiley Periodicals, Inc. [source]