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)

We used a paired-pulse magnetic stimulation technique to study ipsilateral cortico-cortical inhibition of the motor cortex in 48 patients with various neurological disorders and in 20 normal volunteers. In the normal subjects, the first subthreshold conditioning stimulus suppressed responses to the second suprathreshold test stimulus at interstimulus intervals (ISIs) of 1-5 ms (inhibition at short intervals), and facilitated them at ISIs of 8-15 ms (facilitation at long intervals). Patients with motor neuron disease, except those in whom brain stimulation produced control responses that were generated by direct activation of corticospinal neurons (D-waves), had normal inhibition at short intervals. Facilitation at long intervals was not elicited in some patients with amyotrophic lateral sclerosis. Less inhibition at short intervals and normal facilitation at long intervals was found for all the patients with progressive myoclonic epilepsy, a condition in which the excitability of cortical inhibitory interneurons is thought to be affected. Inhibition at short intervals was disturbed, but facilitation at long intervals was intact in the patients with movement disorders (Parkinson's disease, corticobasal degeneration, and Wilson's disease). In these patients, positron emission tomography (PET) studies showed decreased regional cerebral blood flow (rCBF) in the basal ganglia in the relaxed state. However, normal suppression was elicited in the patients with Parkinson's disease with normal rCBF. In four patients with chorea, the time-course of inhibition and facilitation was normal, even though PET studies showed decreased rCBF in the basal ganglia in two of them. Normal inhibition could not be elicited in patients who had a small lesion in the basal ganglia or in the pathway from basal ganglia to the primary motor cortex; the putamen, globus pallidus, and supplementary motor cortex. In contrast, patients who had a lesion in a sensory system (sensory cortex or sensory thalamus) or in the pontine nucleus had normal suppression. We conclude that the results of ipsilateral cortico-cortical inhibition with paired magnetic stimulation reflect the excitability of inhibitory interneurons in the motor cortex and that outputs from the basal ganglia markedly affect this inhibition, but outputs from somato-sensory systems or cerebellum do not. Moreover, dysfunction of the corticospinal tract or spinal motoneurons does not affect results obtained by the paired magnetic stimulation technique when the control responses are generated by I-waves (i.e. descending volleys are produced by transsynaptic activation of the corticospinal tract neurons.
 ...
PMID:Ipsilateral cortico-cortical inhibition of the motor cortex in various neurological disorders. 886 35

Since 1992 there has been renewed interest in pallidotomy now that the limitations and adverse effects of long-term dopaminergic therapy have become more apparent and more difficult to control in patients with advanced Parkinson's disease. The authors describe the effect of pallidotomy in 19 patients, sixteen of whom had advanced Parkinson's disease with painful dystonia and/or response fluctuations with severe akinesia while in "off" and dyskinesias while in "on". One patient had cortico-basal degeneration with rigidity, one patient had secondary dystonia and one had dystonic posturing due to Wilson's disease. Fifteen patients underwent unilateral pallidotomy, four patients had a staged bilateral procedure. Follow-up ranged from 3 to 42 months (mean 18 months). All patients with peak-dose dyskinesias and/or dystonia had marked reduction of symptoms, including the cases of Wilson's disease and secondary dystonia. The akinesia and rigidity scores of Parkinson-patients in "off" were greatly reduced, mainly but not only on the contralateral side. Evaluation by the patients showed remarkable improvement of symptoms in 79%, leading to substantially improved functional abilities in 68%. In this series the decrease in dopamine-response fluctuations, dystonia, hypokinesia and rigidity with functional improvement as judged by examiners and patients reflect a significant regain of independence.
 ...
PMID:Posteroventral pallidotomy in movement disorders. 923 7

Recent developments in molecular genetics have had a profound influence on the diagnosis and classification of inherited movement disorders. Huntington's disease is caused by the expansion of an unstable trinucleotide repeat sequence. Molecular diagnosis can now be performed by a simple PCR-based assay, and the study of the effects of the repeat expansion on the function of the encoded protein will allow to elucidate the molecular pathogenesis of the disease. Wilson's disease is caused by a large number of different mutations, which complicates molecular diagnosis. Genes for a number of inherited dystonic syndromes have been mapped, one of them, the gene for dopa-responsive dystonia, has already been identified. The genetic basis of several other prevalent movement disorders, such as essential tremor and the restless-legs syndrome however, is still obscure. Current research is also directed at the identification of inherited risk-factors in genetically complex movement disorders, such as Parkinson's disease.
 ...
PMID:Advances in the genetics of movement disorders: implications for molecular diagnosis. 924 18

MR imaging examinations of seven patients with a variety of claustral disorders are included in this study. The ages of the patients ranged from 4 to 65 years, and all of them were males. The lesions involving the claustrum comprised cases with asphyxia, Wilson's disease, ischemic white matter disease, thalamic arteriovenous malformation, MELAS syndrome, viral encephalitis and Parkinson's disease.
 ...
PMID:Lesions affecting the claustrum. 974 43

Degenerative diseases of the basal ganglia, such as Huntington's disease (HD), Parkinson's disease, and Wilson's disease, are characterized by motor, cognitive, and psychiatric manifestations. HD, in particular, can be considered a paradigmatic neuropsychiatric disorder that has all three components of the "Triadic Syndromes": dyskinesia, dementia, and depression. The authors examine the phenomenology, prevalence, and management of psychiatric disturbances occurring in diseases of the basal ganglia. They address psychiatric conditions such as depression, mania, psychosis, obsessive-compulsive disorders, aggression, irritability, apathy, sexual disorders, and delirium, discussing subtleties of diagnosis, and making reference to more unusual disorders of the basal ganglia, such as postencephalitic parkinsonism and Fahr's disease.
 ...
PMID:Neuropsychiatry of Huntington's disease and other basal ganglia disorders. 1066 65

Mitochondria have been linked to both necrotic and apoptotic cell death, which are thought to have a major role in the pathogenesis of neurodegenerative diseases. Recent evidence shows that nuclear gene defects affecting mitochondrial function have a role in the pathogenesis of Friedreich's ataxia, Wilson's disease and hereditary spastic paraplegia. There is also accumulating evidence that mitochondrial dysfunction might have a role in the pathogenesis of amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Alzheimer's disease. If this is so, a number of therapeutic targets are implicated that might result in novel treatments for neurodegenerative diseases.
 ...
PMID:Energetics in the pathogenesis of neurodegenerative diseases. 1085 39

We studied the clinical features, laboratory investigation, management and natural history of a cohort of patients with Juvenile Parkinsonism (JP), seen at a tertiary referral centre. JP was defined as Parkinsonism with onset at age 20 years or less. Six patients (five male, one female) entered the study. The mean age at onset of Parkinsonism was 12.5 years (range 7-19) and the mean follow-up time was 49.3 months (range 40-57). Bradykinesia, rigidity, and postural instability were observed in all patients and five subjects had tremor. Dystonia was present in four subjects. Other clinical features were dementia (five subjects), supranuclear ophthalmoparesis (five subjects), seizures (three subjects), multifocal myoclonus (one subject), decreased deep reflexes (one subject), pyramidal signs (one subject). Family history of Parkinson's disease (PD) was positive in one subject. Work-up for Wilson's disease was negative in all patients. Neuroimaging studies showed cortical atrophy in two subjects and mild brainstem atrophy in two others. Sea-blue histiocytes were found in one subject. L-dopa improved the Parkinsonism in all subjects but four rapidly developed fluctuations and dyskinesias, requiring, in one, stereotaxic surgery. After a mean disease duration of 6.5 years, five subjects require assistance for performance of all daily activities. JP is a heterogeneous clinical entity. In the majority of patients, no underlying cause is identified. The unusual clinical features suggest most subjects have a CNS degenerative disease distinct from PD. There is, however, evidence suggesting that PD may rarely cause JP. Gangliosidosis is another cause of L-dopa-responsive JP. Regardless of the cause, in the present study JP displays an aggressive and rapidly progressive course in most patients.
 ...
PMID:Juvenile parkinsonism: a heterogeneous entity. 1105 29

Zinc has several crucial functions in brain development and maintenance: it binds to p53, preventing it from binding to supercoiled DNA and ensuring that p53 cause the expression of several paramount genes, such as the one that encodes for the type I receptors to pituitary adenine cylase-activator peptide (PACAP), which directs embryonic development of the brain cortex, adrenal glands, etc.; it is required for the production of CuZnSOD and Zn-thionein, which are essential to prevent oxidative damage; it is required for many proteins, some of them with Zn fingers, many of them essential enzymes for growth and homeostasis. For example, the synthesis of serotonin involves Zn enzymes and since serotonin is necessary for melatonin synthesis, a Zn deficiency may result in low levels of both hormones. Unfortunately, Zn levels tend to be low when there is excess Cu and Cd. Moreover, high estrogen levels tend to cause increased absorption of Cu and Cd, and smoking and eating food contaminated with Cd result in high levels of the latter. Furthermore, ethanol ingestion increases the elimination of Zn and Mg (which acts as a cofactor for CuZnSOD). Increased Cu levels may also be found in people with Wilson's disease, which is a rather rare disease. However, the heterozygote form (only one faulty copy of the chromosome) is not so rare. Therefore, the developing fetus of a pregnant women who is low in Zn and high in Cu may experience major difficulties in the early development of the brain, which may later manifest themselves as schizophrenia, autism or epilepsy. Similarly, a person who gradually accumulates Cu, will tend to experience a gradual depletion of Zn, with a corresponding increase in oxidative damage, eventually leading to Parkinson's disease. Also discussed are the crucial roles of histidine, histamine, vitamin D, essential fatty acids, vitamin E, peroxynitrate, etc. in the possible oxidative damage involved in these mental diseases.
 ...
PMID:Micronutrient accumulation and depletion in schizophrenia, epilepsy, autism and Parkinson's disease? 1138 83

Wilson's disease (WD) patients often present with Parkinson's disease (PD). Furthermore, most patients with PD have reduced ceruloplasmin, a characteristic of Wilson's disease. WD is an autosomal recessive disease (requires two faulty copies of a gene to produce a homozygote individual) that afflicts 1 in 1000 people. However, the number of people with one faulty copy (heterozygotes) is much larger, probably about 2% of the population. I hypothesize that the large number of heterozygotes for WD are at greatly increased risk for idiopathic PD, because these people accumulate free copper in the basal ganglia at a slower rate than homozygotes, which accounts for the fact that PD usually develops after 40 years of age. In WD, a ceruloplasmin deficiency results in accumulation of free Cu in the liver, brain, kidneys, etc. The excess Cu results in impaired Zn absorption, which would account for the low levels of Zn in the brains of PD patients. Moreover, the high levels of Fe found in the substantia nigra of PD patients may perhaps be explained by free Cu binding to iron binding protein-1 (IBP-1), causing it to malfunction and preventing it from detaching itself from the transferrin receptor (TfR) inhibition gene, resulting in expression of TfR even when the cell has plenty of Fe. The gradual accumulation of Fe and Cu would explain the damage inflicted on the substantia nigra by free radicals catalyzed by these two metals and which is exacerbated by the low levels of CuZnSOD, due to the Zn deficiency mentioned above. Moreover, if this hypothesis is correct, then PD could be used to help discover the gene (or genes) responsible for WD and vice versa. Furthermore, idiopathic PD could be prevented by identifying the heterozygote individuals and providing them with Zn supplementation, Cu chelation therapy and phlebotomy to eliminate Fe.
 ...
PMID:Is Parkinson's disease the heterozygote form of Wilson's disease: PD = 1/2 WD? 1142 82

THALAMUS: The human thalamus is a nuclear complex located in the diencephalon and comprising of four parts (the hypothalamus, the epythalamus, the ventral thalamus, and the dorsal thalamus). The thalamus is a relay centre subserving both sensory and motor mechanisms. Thalamic nuclei (50-60 nuclei) project to one or a few well-defined cortical areas. Multiple cortical areas receive afferents from a single thalamic nucleus and send back information to different thalamic nuclei. The corticofugal projection provides positive feedback to the "correct" input, while at the same time suppressing irrelevant information. Topographical organisation of the thalamic afferents and efferents is contralateral, and the lateralisation of the thalamic functions affects both sensory and motoric aspects. Symptoms of lesions located in the thalamus are closely related to the function of the areas involved. An infarction or haemorrhage thalamic lesion can develop somatosensory disturbances and/or central pain in the opposite hemibody, analgesic or purely algesic thalamic syndrome characterised by contralateral anaesthesia (or hypaesthesia), contralateral weakness, ataxia and, often, persistent spontaneous pain. BASAL GANGLIA: Basal ganglia form a major centre in the complex extrapyramidal motor system, as opposed to the pyramidal motor system (corticobulbar and corticospinal pathways). Basal ganglia are involved in many neuronal pathways having emotional, motivational, associative and cognitive functions as well. The striatum (caudate nucleus, putamen and nucleus accumbens) receive inputs from all cortical areas and, throughout the thalamus, project principally to frontal lobe areas (prefrontal, premotor and supplementary motor areas) which are concerned with motor planning. These circuits: (i) have an important regulatory influence on cortex, providing information for both automatic and voluntary motor responses to the pyramidal system; (ii) play a role in predicting future events, reinforcing wanted behaviour and suppressing unwanted behaviour, and (iii) are involved in shifting attentional sets and in both high-order processes of movement initiation and spatial working memory. Basal ganglia-thalamo-cortical circuits maintain somatotopic organisation of movement-related neurons throughout the circuit. These circuits reveal functional subdivisions of the oculomotor, prefrontal and cingulate circuits, which play an important role in attention, learning and potentiating behaviour-guiding rules. Involvement of the basal ganglia is related to involuntary and stereotyped movements or paucity of movements without involvement of voluntary motor functions, as in Parkinson's disease, Wilson's disease, progressive supranuclear palsy or Huntington's disease. The symptoms differ with the location of the lesion. The commonest disturbances in basal ganglia lesions are abulia (apathy with loss of initiative and of spontaneous thought and emotional responses) and dystonia, which become manifest as behavioural and motor disturbances, respectively.
 ...
PMID:Functional anatomy of thalamus and basal ganglia. 1219 99


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