Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption-a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic alpha-tocopherol transfer protein also cause vitamin E deficiency-defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of alpha-tocopherol is recommended to obtain "optimal plasma alpha-tocopherol concentrations" (30 microM or greater).
 ...
PMID:Vitamin E in humans: demand and delivery. 883 30

We report a 43-year-old woman who died after 18 years history of parkinsonism. She was well until 25 years of the age (1976) when she noted a difficulty in stepping her feet. In the next year, she started to drag her feet. She was treated with levodopa with good response, however, she developed dyskinesia when she was 33 years of the age. She was evaluated in another hospital in 1984. She showed normal intelligence, normal ocular movement, masked face, small voice, small step gait, stooped posture, freezing of the gait, retropulsion, and cogwheel rigidity in limbs. No tremor or ataxia was noted. She received left ventrolateral thalamotomy at that time. Rigidity on the right side markedly reduced, however, she continued to show bradykinesia and motor fluctuations. On August 1 of 1994, she developed fever of 40 degrees C and dyspnea. On the next day, she expired from acute respiratory distress. She was able to walk unsupported until just before her last admission. The patient was discussed in a neurological CPC. The chief discussant arrived at the conclusion that this patient had Lewy body-positive young onset Parkinson's disease. Opinions were divided into two groups, i.e., young onset Lewy-body positive Parkinson's disease and Lewy-body negative young onset parkinsonism. Post-mortem examination revealed moderate loss of pigmented neurons in the substantia nigra more in the ventro-lateral part. Lewy bodies were found in the remaining neurons. Lewy bodies were more frequently seen in the locus coeruleus, although neuronal loss was less prominent in the locus coeruleus. The dorsal vagal motor nucleus showed moderate loss of neurons. Otherwise, the central nervous system was unremarkable. To our knowledge, this patient had the second youngest age of the onset so far reported in the literature for Lewy-body positive typical Parkinson's disease.
 ...
PMID:[A 43-year-old woman with 18 years history of parkinsonism]. 892 38

Rapid progress has been made in the identification of mitochondrial DNA mutations which are typically associated with diseases of the nervous system and muscle. The well established mitochondrial disorders are maternally inherited and males and females are equally affected. An exception is Leber's hereditary optic atrophy (LHON) which is observed much more frequently in males than in females. There are three common point mutations in LHON which can be homoplasmic or heteroplasmic. In mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) most mutations are single base changes and lie within the tRNA-Leu gene. Point mutations in myoclonic epilepsy with ragged red fibres (MERRF) usually occur within the tRNA-Lys gene but mutations of the tRNA-Leu gene are also observed. MELAS and MERRF mutations are heteroplasmic and there is considerable clinical overlap between these diseases. Point mutations within the ATPase6 gene result in either neuropathy, ataxia and retinitis pigmentosa (NARP) or in Leigh's syndrome. The latter occurs if the mutation is present in the majority of mitochondria (extreme heteroplasmy). Finally, mitochondrial DNA deletions are the cause underlying Kearns-Sayre syndrome (KSS). Apart from the well-established mitochondrial diseases, there is increasing evidence that mitochondrial mutations may also play a role in the neurodegenerative disorders Parkinson, Alzheimer and Huntington disease. The complex I defect found in Parkinson disease is especially interesting in this respect. However, no causative mitochondrial mutation has as yet been established in any of these three common disorders.
 ...
PMID:Recent developments in the molecular genetics of mitochondrial disorders. 951 82

By using three-dimensional magnetic resonance imaging-based volumetry, we studied atrophy of the caudate nucleus, putamen, brainstem, and cerebellum in patients with idiopathic Parkinson's syndrome (IPS, n = 11), progressive supranuclear palsy (PSP, n = 6), and multiple system atrophy with predominant parkinsonism (MSA-P, n = 12) or ataxia (MSA-C, n = 17). Patients were compared with a total of 46 controls, of whom 16 were age matched. Mean striatal, cerebellar, and brainstem volumes were normal in patients with IPS. We found significant reductions in mean striatal and brainstem volumes in patients with MSA-P, MSA-C, and PSP, whereas patients with MSA-C and MSA-P also showed a reduction in cerebellar volume. On an individual basis, volumes of structures in patients with MSA and PSP showed an extensive overlap with the normal range with the exception of brainstem volumes in patients with MSA-C. Therefore, groups could not be discriminated on the basis of individual structure volumetry. Application of stepwise discriminant analysis, however, allowed discrimination of all 12 patients with MSA-P, 15 of 17 patients with MSA-C, and 5 of 6 patients with PSP from the normal and IPS cohorts. However, patients with IPS could not be separated from controls and patients with MSA-P could not be separated from patients with PSP. In conclusion, total intracranial volume-normalized magnetic resonance imaging-based volumetric measurements provide a sensitive marker to discriminate typical and atypical parkinsonism.
 ...
PMID:Magnetic resonance imaging-based volumetry differentiates idiopathic Parkinson's syndrome from multiple system atrophy and progressive supranuclear palsy. 989 79

Quantitative gait analysis has been used to elucidate characteristic features of neurological gait disturbances. Although a number of studies compared single patient groups with controls, there are only a few studies comparing gait parameters between patients with different neurological disorders affecting gait. In the present study, gait parameters were compared between control subjects, patients with parkinsonian gait due to idiopathic Parkinson's disease, subjects suffering from cerebellar ataxia and patients with gait disturbance due to subcortical arteriosclerotic encephalopathy. In addition to recording of baseline parameters during preferred walking velocity, subjects were required to vary velocity from very slow to very fast. Values of velocity and stride length from each subject were then used for linear regression analysis. Whereas all patient groups showed slower walking velocity and reduced step length compared with healthy controls when assessed during preferred walking, patients with ataxia and subcortical arteriosclerotic encephalopathy had, in addition, increased variability of amplitude and timing of steps. Regression analysis showed that with changing velocity, subjects with Parkinson's disease changed their stride length in the same proportion as that measured in controls. In contrast, patients with ataxia and subcortical arteriosclerotic encephalopathy had a disproportionate contribution of stride length when velocity was increased. Whereas the findings in patients with Parkinson's disease can be explained as a reduction of force gain, the observations for patients with ataxia and subcortical arteriosclerotic encephalopathy reflect an altered spatiotemporal gait strategy in order to compensate for instability. The similarity of gait disturbance in subcortical arteriosclerotic encephalopathy and cerebellar ataxia suggests common mechanisms.
 ...
PMID:Comparative analysis of gait in Parkinson's disease, cerebellar ataxia and subcortical arteriosclerotic encephalopathy. 1038

Movement disorders is a term applied for a heterogeneous group of diseases and syndromes sharing deficits of voluntary motor function or movement patterns. In clinical practice, the term movement disorders is usually employed to designate those syndromes and diseases that are linked to a pathology or dysfunction of cortico-basal ganglia circuits. The last years have witnessed a rapid expansion in our understanding of the etiological and pathophysiological factors underlying movement disorders such as Parkinson's disease or dystonia. The discovery of new gene mutations is bound to give rise to new insights into the molecular pathogenesis of movement disorders related to neurodegenerative processes. It is already becoming apparent that pathological protein aggregation may be a common link in the neuronal degeneration underlying such diverse entities as spinocerebellar ataxia, idiopathic torsion dystonia and Parkinson's disease. So far, these new findings have not been translated into new forms of symptomatic or preventive therapies. Nevertheless, symptomatic treatment of movement disorders, as evident in the field of Parkinson's disease, is one of the most rewarding and innovative areas of neurological therapy.
 ...
PMID:What is new in movement disorders? 1052 91

The alpha-ketoglutarate dehydrogenase complex (KGDHC) is an important mitochondrial constituent, and deficiency of KGDHC is associated with a number of neurological disorders. KGDHC is composed of three proteins, each encoded on a different and well-characterized gene. The sequences of the human proteins are known. The organization of the proteins into a large, ordered multienzyme complex (a "metabolon") has been well studied in prokaryotic and eukaryotic species. KGDHC catalyzes a critical step in the Krebs tricarboxylic acid cycle, which is also a step in the metabolism of the potentially excitotoxic neurotransmitter glutamate. A number of metabolites modify the activity of KGDHC, including inactivation by 4-hydroxynonenal and other reactive oxygen species (ROS). In human brain, the activity of KGDHC is lower than that of any other enzyme of energy metabolism, including phosphofructokinase, aconitase, and the electron transport complexes. Deficiencies of KGDHC are likely to impair brain energy metabolism and therefore brain function, and lead to manifestations of brain disease. In general, the clinical manifestations of KGDHC deficiency relate to the severity of the deficiency. Several such disorders have been recognized: infantile lactic acidosis, psychomotor retardation in childhood, intermittent neuropsychiatric disease with ataxia and other motor manifestations, Friedreich's and other spinocerebellar ataxias, Parkinson's disease, and Alzheimer's disease (AD). A KGDHC gene has been associated with the first two and last two of these disorders. KGDHC is not uniformly distributed in human brain, and the neurons that appear selectively vulnerable in human temporal cortex in AD are enriched in KGDHC. We hypothesize that variations in KGDHC that are not deleterious during reproductive life become deleterious with aging, perhaps by predisposing this mitochondrial metabolon to oxidative damage.
 ...
PMID:The alpha-ketoglutarate dehydrogenase complex. 1067 30

Fifty-eight patients, 36 with essential tremor (ET) and 22 with Parkinson's disease (PD), received deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) nucleus. The mean follow-up was 17 months for ET and 21 months for PD patients. Stimulation parameters were adjusted as needed, at various intervals after surgery. Results were assessed using routine clinical evaluation and established outcome scales. All patients needed incremental increase in stimulation parameters at various intervals during the first 6-12 months after surgery. The mean voltage 1 week postoperatively was 1. 45 V in PD patients, and 1.37 V in ET patients. Twelve months later, the figures were 2.14 V in PD and 2.25 V in ET patients. At 1 year, the Essential Tremor Rating Scale (ETRS) improved from 54 to 28 (p < 0.0001). The motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) improved from 37 to 26 (p < 0.01). Tremor items of the UPDRS improved more markedly (p < 0.0001). One week postoperatively 90% of PD, and 89% of ET patients were tremor free. One year later, 70% of PD and 60% of ET patients remained mostly tremor free. Upon switching off stimulation, there was a clear tendency for tremor rebound (p = 0.07) in the PD group, requiring continuous 24-hour stimulation in some patients. Permanent non-adjustable ataxia was induced by stimulation in 2 PD patients.
 ...
PMID:Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor. 1085 80

Local field potentials (LFPs) were recorded in seven unanaesthetized patients between the four adjacent contacts of a macroelectrode stereotactically implanted for the treatment of tremor. The LFPs were presumed to arise predominantly from the nucleus ventralis intermedius (Vim) of the thalamus, the implantation target. They were recorded simultaneously with the ipsilateral EEG and contralateral EMG during an isometric contraction or at rest. The patients had a history of either isolated tremor (essential tremor, n = 2; benign tremulous Parkinson's disease, n = 1) or tremor with signs of a cerebellar syndrome (multiple sclerosis, n = 3; essential tremor and ataxia, n = 1), although clinical tremor was absent at the time of recording because of a temporary microthalamotomy effect in four patients. In patients with isolated tremor, oscillatory activity picked up by contacts in Vim (cerebellar thalamus) was invariably coherent with that in the sensorimotor cortex or contracting muscle in the 8-27 Hz range. Such coherence was absent in two of the four subjects with tremor associated with a cerebellar syndrome. Coherence between LFPs recorded from more caudally placed contacts and the sensorimotor cortex or contracting muscle was negligible in all patients. These caudally placed contacts demonstrated the highest sensory evoked potential in response to median nerve stimulation. Oscillatory activity in the cerebellar thalamus (Vim) lagged behind that in both cortex and muscle. Coherent activity between the cerebellar thalamus (Vim) and the cortex persisted at rest. It is suggested that rhythmicities in the 8-27 Hz range could provide the basis for a temporal framework that is widely distributed within the motor system.
 ...
PMID:Coherence between cerebellar thalamus, cortex and muscle in man: cerebellar thalamus interactions. 1086 57

Epidemiological and neuropathological series have identified three predominant dementing processes; Alzheimer's disease (AD), vascular dementia (VaD) and dementia associated with Lewy bodies (termed Parkinson's disease dementia (PDD) in this paper). While each has its own distinguishing features and by definition all impact upon day to day functioning, no random community derived sample has examined clinical features as defined by gait and balance abnormalities and compared disability ratings of the three dementias simultaneously. Six hundred and forty-seven community dwelling subjects participated in the Sydney Older Persons Study and of these 537 participated in a medical assessment. Of these 537,482 informants rated disability. Gait and balance abnormalities of the three major dementias were identified and the association of the dementias with disability examined. The three major dementias showed evidence of both slowing and ataxia in gait and balance tests. This was maximal in those with PDD. Similarly, all showed evidence of disability that was maximal in those with PDD. In conclusion, this study has identified that gait abnormalities are present in all three dementias to a varying degree. It is hypothesised that the varying levels of disability observed are a consequence of the varying levels of motor impairment, resulting in greater levels of disability in those with PDD.
 ...
PMID:Motor function and disability in the dementias. 1104 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>