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

Spontaneous blink rates are controlled by a definable neural system originating in PPRF with facilitatory modulation from SN and superior colliculus and inhibitory modulation provided by cerebellum and occipital cortex. The thalamus may also be involved but the result of its influence is not clear. Reflex blinking is often reduced when spontaneous blink rate is increased and the reverse applies as well. The anatomic control of reflex is primarily in structures in the caudal half of pontine tegmentum and rostral midbrain. However, SN and cerebellum and other structures that regulate blink rate also modulate reflex blinking. Neurochemical control as determined by neuropharmacological experiments is exerted by dopaminergic, cholinergic and GABAergic systems of brain stem. Dopamine activity correlates directly with blink rate whereas agonism of the other two relevant neurotransmitter systems may inhibit blink rate. Clinical implications in central nervous system disease are currently restricted to Parkinson's disease, schizophrenia and autism. In the former illness, reduced blink rate signifies a worsening of the illness and a significant increase in blink rate in patients treated with dopamine agonist may be a harbinger of agonist-induced dyskinesia. In schizophrenia, increased blink rate, even in medication-naive subjects, may signify involvement of the structures that regulate blinking. This is important because these structures are rarely invoked as sites of potential pathophysiological import in schizophrenia. Similar considerations apply to autism except that increased blinking more clearly differentiates this disorder from other forms of retardation.
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PMID:Blinking. 248 18

The findings in this feline study indicate that the enkephalin-positive subcommissural part of the globus pallidus, which is known to contain GABA and cholinergic cells projecting to the cortex, is innervated by the anterodorsal region of the caudate nucleus, but not by the core. Like stimulation of a particular subclass of dopamine receptors in the anterodorsal region of the caudate nucleus, inhibition of the GABA receptors in the noted part of the globus pallidus resulted in orofacial dyskinesia, viz. tic-like contractions of the facial, eye and ear muscles, and tongue protrusions. This phenomenon was elicited by intrapallidal injections of the GABA antagonist picrotoxin in a dose-dependent manner and could be attenuated by the GABA agonist muscimol. Previous studies have already shown that neither stimulation of the dopamine receptors in the core of the caudate nucleus nor any manipulation with the first- and second-order output-stations of the latter brain region, viz. (a) those regions of the substantia nigra, pars reticulata which receive afferents from the caudate nucleus, and (b) those regions of the intermediate layers of the superior colliculus which receive afferents from the latter nigral region, ever resulted in orofacial dyskinesia. These findings support the hypothesis that the anatomically distinct input-output channels of the caudate nucleus are differentially involved in orofacial dyskinesia. The clinical impact of these findings is discussed in view of the L-3,4-dihydroxyphenylalanine-induced tardive dyskinesia in man. In addition, the relevance of the anatomical data is discussed in view of the co-occurrence of Parkinson's Disease and Dementia of Alzheimer-type in certain patients.
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PMID:Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia. 256 20

1. Experimental models of ballism, chorea and Parkinson's disease have been developed in the primate, and the underlying neural mechanisms which mediate these disorders of movement have been investigated using the 2-deoxyglucose uptake technique. 2. In ballism, the subthalamic nucleus is either lesioned or underactive. Because of the excitatory nature of subthalamic efferent fibres, this leads to abnormal underactivity of neurons in the medical segment of the globus pallidus which project to the ventral anterior and ventral lateral nuclei of the thalamus, and to the pedunculopontine nucleus of the caudal midbrain. 3. In chorea, there is underactivity of GABAergic striatal (putaminal) neurons which project to the lateral segment of the globus pallidus. This leads to overacting of lateral pallidal neurons and, thus, physiological inhibition of the subthalamic nucleus. Common neural mechanisms, therefore, underlie the appearance of dyskinesia in ballism and chorea. 4. In parkinsonism, there is overactivity of putaminal neurons projecting to the lateral pallidal segment. This results in excessive inhibition of lateral pallidal neurons and, as a consequence, disinhibition of the subthalamic nucleus. Overactivity of the subthalamic nucleus provides excessive drive upon medial pallidal neurons projecting to thalamic and pedunculopontine nuclei.
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PMID:Neural mechanisms in disorders of movement. 256 16

Nine patients with advanced Parkinson's disease were started on continuous enteral levodopa infusions during the past 3 years. Six have remained on the infusion system for 1 to 28 months. All patients experienced immediate amelioration of motor fluctuations, and 5 patients continue to obtain relief. One patient found that his ability to achieve the "on" state without unacceptable dyskinesia waned. Experience thus far indicates that continuous long-term levodopa infusions are a practical but complex form of therapy for patients failing more conventional treatment.
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PMID:Experience with continuous enteral levodopa infusions in the treatment of 9 patients with advanced Parkinson's disease. 258 63

The efficacy of controlled-release Sinemet was evaluated in a 52-week open trial involving 20 patients (14 men, 6 women; mean age 66 years, range 56 to 82) with idiopathic Parkinson's disease of 8 years' mean duration. The mean daily dosage of levodopa was 662.5 mg (200 to 1600 mg) on entering the study and 800 mg (200 to 2400 mg) after 52 weeks. The mean number of daily doses was reduced from 5.0 (2 to 16) at entry to 3.3 (1 to 6) after 52 weeks. Rigidity, tremor, and bradykinesia were scored at 3 intervals during baseline and 8 intervals during the study on controlled-release levodopa. All parameters improved, with maximum improvement seen at week 12. Side effects were less frequent on the controlled-release preparation. After 5 months, 1 patient developed protracted dyskinesia with freezing episodes and end-of-dose deterioration on dose frequency reduction.
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PMID:Sinemet CR in the treatment of patients with Parkinson's disease already on long-term treatment with levodopa. 258 67

Sinemet CR, a controlled-release form of carbidopa/levodopa, was administered for 36 or 39 months to 8 patients with Parkinson's disease in an open-label study. On standard Sinemet each patient had experienced "wearing off" phenomena, and 5 had also experienced random "off" episodes. Daily "on" time, dyskinesia time, disability score, levodopa dosage requirement, and dosing frequency on Sinemet CR were compared with baseline values on standard Sinemet therapy. After both 3 and 36 or 39 months of Sinemet CR therapy, 5 patients showed increased daily "on" time compared with baseline. All 8 required fewer daily doses after 3 months on Sinemet CR, but only 3 were still taking fewer doses after 36 or 39 months. Disability scores remained essentially unchanged. Patients continued to elect to remain on Sinemet CR over the 3-year period, citing improved predictability of response and less severe and precipitous "off" episodes as the main reasons. This experience suggests that patient acceptance of Sinemet CR remains high. A modest improvement in "on" time can be achieved and maintained in some patients for as long as 3 years. However, as with standard Sinemet, dosing frequency for Sinemet CR may need to be gradually increased with time in order to maintain benefits achieved.
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PMID:Long-term clinical efficacy of Sinemet CR in patients with Parkinson's disease. 258 69

One hundred and twenty nine de novo patients with idiopathic Parkinson's disease are being followed over a 5 year period in a double-blind multicentre study comparing low-dose bromocriptine (less than 30 mg/day) with low-dose levodopa-carbidopa (less than 600/150 mg/day). Sixty six patients have been randomised to bromocriptine and 63 patients to levodopa-carbidopa. Improvement has been greater in the levodopa-carbidopa group than in the bromocriptine group. Involuntary movements have so far only occurred in patients on levodopa-carbidopa, the incidence being much lower than is usually described with conventional doses. Mild, end-of-dose failure has occurred in both treatment groups; however, no patient has developed the "on-off" phenomenon. Low-dose levodopa-carbidopa appears to be a more effective anti-Parkinsonian treatment than low-dose bromocriptine but more prone to cause dyskinesia.
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PMID:The Sydney Multicentre Study of Parkinson's disease: a report on the first 3 years. 264 7

In eight patients with advanced Parkinson's disease, we performed autograft transplantation of adrenal medulla to the head of the caudate nucleus. Our technique was similar to that developed by Madrazo and co-workers in Mexico City. No major perioperative complications occurred except for somnolence in one patient for 8 days postoperatively. The follow-up period has been at least 6 months in seven of the patients, and only limited benefit has been apparent. The early morning Parkinson examination score in the "off" (unmedicated) state was significantly improved in one patient and slightly better in the other six. Diary card entries suggested a mild trend toward improvement (not statistically significant). Four of the seven patients were taking less levodopa 6 months after the operation than they had been preoperatively; three of five patients were no longer taking dopamine agonists postoperatively. We cannot exclude a placebo effect contributing to any of this improvement. A reduction in medication-induced dyskinesia was also noted, but this result may have been due to adjustments in doses or a slightly less potent effect of medication (or both factors). In summary, we have not yet been able to replicate the dramatic success reported for adrenal medullary transplantation by Madrazo's group, although our patients may have experienced mild to moderate improvement. We continue to maintain follow-up surveillance of these patients.
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PMID:Adrenal medullary autograft transplantation into the striatum of patients with Parkinson's disease. 264 48

"Wearing-off" effect, the most common form of levodopa-induced fluctuations, seems to be related to the short plasma half-life of the drug. More sustained plasma levodopa levels may be achieved with a new controlled-release formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less than 0.001). However, this was at the expense of reducing the "on" time (without dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the total "on" time did not significantly change. In a long-term follow-up of 18 patients, the "on" time with dyskinesia and morning dystonia significantly increased (p less than 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p less than 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa-related fluctuations.
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PMID:Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations. 268 15

134 cases of dyskinesia caused by various CNS diseases were treated with a new type of DA blocker L-Stepholidine (1-SPD). Good response was obtained in 72% (29/40) of L-dopa induced abnormal involuntary movements in Parkinson disease, 79% (34/43) of Tourette syndrome, and 65% (15/23) of tardive dyskinesia through a short-term follow-up. No serious side effects were found within the therapeutic dosage of 50-225mg/day The results showed that L-SPD is a new type of anti-dyskinesia agent deserving further pharmacological investigation.
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PMID:[Clinical study on the treatment of dyskinesia by L-stepholidine]. 270 Jun 94


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