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)

Patients with parkinsonism can be classified as clinical definite, probable, possible, or unlikely Parkinson's disease (PD). Possible PD includes patients with PD according to conventional diagnostic criteria and with at least a moderate response to dopamine agonists. However, these patients have clinical features that may reduce the probability for idiopathic PD. The objective of this study was to clinically characterize patients with possible disease in a prevalence study of PD and to indicate the frequency of idiopathic PD in this group of patients. The diagnostic re-evaluation was based on detailed MRI examinations and investigations of dopaminergic drug response after several years of treatment. In a community-based prevalence study in Norway, comprising 245 PD patients, we found 36 patients (15%) with clinical possible PD. The patients with possible disease had significant and clinically important differences in demographic and disease characteristics compared to patients with definite and probable PD. Possible PD patients were older at disease onset, more disabled, and had more neurobehavioral disorders. MRI examinations of 14 of the 36 patients with possible PD in the prevalence study revealed significant group effects compared to an age-matched control group, with reduced pars compacta width and increased cortical atrophy. In individual patients, signal attenuation consistent with vascular lesions of the basal ganglia contributed to diagnostic reclassification. Dopaminergic drug withdrawal revealed no response in 4 of 12 examined patients. Two of the remaining eight patients had a clear short-duration drug response. Six patients had only a varying degree of long-duration response. The re-evaluation of diagnosis indicates that probably less than half of the patients with clinical possible PD have idiopathic disease. Patients with atypical features and diagnosed as possible PD should thus be excluded from studies with a presumed high specificity for idiopathic PD.
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PMID:Patient characteristics, MRI examination, and dopaminergic drug response in clinical possible Parkinson's disease. 897 7

Drug-induced parkinsonism (DIP) is frequent. The list of drugs able to induce parkinsonism is long and probably incomplete, because new drugs, with previously unknown antidopaminergic activity, are constantly being added. Not all the drugs have the same potency for inducing parkinsonism. We classify these drugs in three groups: (1) drugs with obvious antidopaminergic activity which regularly induce parkinsonism; (2) drugs able to induce parkinsonism in particular individuals and (3) drugs which may aggravate Parkinson's disease treated with levodopa. The reports of isolated cases of parkinsonism induced by widely-used drugs (drugs in group 2) may be the result of either an idiosyncratic side effect or a misdiagnosis of parkinsonism. The antidopaminergic activity of the drugs of this group is weak and not sufficiently demonstrated. Maybe, in these cases, the blockage of other neurotransmitters different from dopamine plays a role in the induction of parkinsonism. Probably, the number of patients with DIP is higher than reported or detected, because many patients suffer from weak symptoms that quickly disappear after drug withdrawal. One of the main points of interest is knowing the list, because all these drugs, specially those of group 1, should be avoided or used with caution in the treatment of some common symptomatic problems in patients with Parkinson's disease, such as depression, arterial hypertension, diabetes mellitus and cardiac disorders. The precautions should extent to other populations especially susceptible to suffer from DIP, such as the elderly or patients with other neurodegenerative disorders, such as Alzheimer's disease.
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PMID:Drugs inducing or aggravating parkinsonism: a review. 913 99

There has been a resurgence in the use of neurosurgical procedures for the treatment of Parkinson's disease (PD). Pallidotomy has become a widely performed procedure on the basis of reports which describe marked reduction of levodopa-induced dyskinesias and variable improvement in parkinsonism. Preliminary reports of the effects of globus pallidus internus (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) have also been promising. At 6-month follow up, a cohort of our first 40 patients undergoing pallidotomy demonstrated the following mean improvements when examined after drug withdrawal (off) and under optimal medication (on): total motor off scores-31%; total off activities of daily living scores-30%; and total on dyskinesias-63% (contralateral and ipsilateral dyskinesias improved 82% and 50%, respectively). Although improvements in contralateral dyskinesias and total off parkinsonism were sustained at 2-year follow up (N = 11), benefit for ipsilateral dyskinesias was lost after 1-year follow up (N = 24). and postural stability and gait improvements lasted only 3-6 months. On-period, levodopa-resistant symptoms did not benefit from pallidotomy. Mean improvements in 8 patients undergoing GPi DBS (4 unilateral and 4 bilateral) at 3 months were as follows: total motor off scores-27%; total off activities of daily living scores-26%; and total on dyskinesias-60%. At most recent follow up, 6 patients with STN DBS (5 bilateral and 1 unilateral) showed the following mean improvements: total motor off scores-41%; total motor on scores-27%; total off activities of daily living scores-40%; and total on dyskinesias 41%. Pallidotomy reduces dyskinesias and off disability. GPi DBS may have effects similar to pallidotomy, but might be safer when bilateral procedures are required. Bilateral STN DBS may improve off parkinsonism more than other procedures and might also improve on-period motor function. A randomized trial will be required to determine which procedure is most effective for patients with different clinical features.
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PMID:Pallidotomy and deep brain stimulation of the pallidum and subthalamic nucleus in advanced Parkinson's disease. 961 22

A retrospective study was carried out to investigate the evolution of patients diagnosed with cinnarizine-induced parkinsonism (CIP) over the past 15 years. A total of 74 cases of CIP were found among 172 patients with drug-induced parkinsonism (DIP). Both CIP and other DIP were significantly more frequent in women. No clinical differences between CIP and other DIP were found. Most of the patients (66 of 74) completely recovered after cinnarizine withdrawal in 1-16 months. Eleven patients later developed Parkinson's disease; four of them had previously recovered. Five patients had tardive dyskinesia. CIP accounts for a high proportion of DIP referred to neurologists in populations in which cinnarizine is widely prescribed. The symptoms typically resolve after drug withdrawal, although complete recovery may take more than 1 year.
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PMID:Cinnarizine-induced parkinsonism: ten years later. 1034 90

Neuroleptic malignant syndrome is a clinical syndrome characterized by fever, muscle rigidity, and mutism. Some patients with neuroleptic syndrome may have elevated creatine phosphokinase values and abnormal liver aminotransferase values. Precipitating factors are important clues for prompt diagnosis. Typical precipitating factors include antipsychotic agents and major tranquilizers. In Parkinson disease, drug withdrawal, menstruation, and hyponatremia are precipitating factors. We report a case of neuroleptic malignant syndrome in a patient with Parkinson disease and hypernatremia. In addition, we hypothesized that sudden change of sodium concentrations in the central nervous system could trigger neuroleptic malignant syndrome in patients with Parkinson disease. According to our experience, neuroleptic malignant syndrome is a clinical diagnosis and prompt diagnosis avoids unnecessary, expensive work-ups.
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PMID:Acute hypernatremia and neuroleptic malignant syndrome in Parkinson disease. 1040 64

Certain dopaminergic anti-Parkinson drugs (ergolines) have repeatedly been identified as a cause of pleuropulmonary disease with a focus on serosal cell damage. Recently, a pathogenetic link between ergolines and prior asbestos exposure was suggested, as regards the development of pleural pathology. This report describes a patient with idiopathic Parkinson's disease, who was on a multiple drug regimen including low dose cabergoline. The patient developed a febrile illness with widespread bilateral lung infiltrations nonresponsive to beta-lactam and macrolide antibiotics. Bronchoalveolar lavage and transbronchial lung biopsy showed a "hypersensitivity-like" interstitial lung disease, which cleared almost completely within 2 months after simple drug withdrawal. Circumstantial evidence suggests a so far undescribed adverse lung reaction to cabergoline, devoid of the more usual pleural changes.
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PMID:Low dose cabergoline induced interstitial pneumonitis. 1057 51

We describe demographic, clinical, laboratory and aetiological findings in 93 consecutive patients with rapid eye movement (REM) sleep behaviour disorder (RBD), which consists of excessive motor activity during dreaming in association with loss of skeletal muscle atonia of REM sleep. The patients were seen at the Mayo Sleep Disorders Center between January 1, 1991 and July 31, 1995. Eighty-one patients (87%) were male. The mean age of RBD onset was 60.9 years (range 36-84 years) and the mean age at presentation was 64.4 years (37-85 years). Thirty-two per cent of patients had injured themselves and 64% had assaulted their spouses. Subdural haematomas occurred in two patients. Dream content was altered and involved defence of the sleeper against attack in 87%. The frequency of nocturnal events decreased with time in seven untreated patients with neurodegenerative disease. MRI or CT head scans were performed in 56% of patients. Although four scans showed brainstem pathology, all of these patients had apparently unrelated neurodegenerative diseases known to be associated with RBD. Neurological disorders were present in 57% of patients; Parkinson's disease, dementia without parkinsonism and multiple system atrophy accounted for all but 14% of these. RBD developed before parkinsonism in 52% of the patients with Parkinson's disease. Five of the 14 patients with multiple system atrophy were female, and thus the strong male predominance in RBD is less evident in this condition. Psychiatric disorders, drug use or drug withdrawal were rarely causally related to RBD. Clonazepam treatment of RBD was completely or partially successful in 87% of the patients who used the drug. We conclude that RBD is a well-defined condition and that descriptions from different centres are fairly consistent. It is commonest in elderly males and may result in serious morbidity to patients and bed partners. There is a strong relationship to neurodegenerative disease, especially Parkinson's disease, multiple system atrophy and dementia, and neurologists should explore the possibility of RBD in patients with these conditions. RBD symptoms may be the first manifestations of these disorders and careful follow-up is needed. Neuroimaging is unlikely to reveal underlying disorders not suspected clinically. We confirm the effectiveness of clonazepam, but note that attention to the safety of the bed environment may be sufficient for patients with contraindications to the drug.
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PMID:Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. 1064 40

In the present investigations continuous intraduodenal infusion of levodopa has been given to patients with advanced Parkinson's disease during 6 months (seven patients) and 2.5 years (two patients). The plasma concentration and the effects on motility have been studied at the start, at 3 and 6 months and after 2.5 years. The individually titrated steady state plasma concentrations (C(ss)) for satisfactory mobility was found to be decreased by the time, and already after 1 month of intraduodenal infusion C(ss) was decreased by about 50%. The obtained data indicate an increased sensitivity with time to levodopa, interpreted as a consequence of disappearing tolerance by the controlled drug delivery. Blood pressure and heart rate were studied in spontaneous hypertensive rats during continuous administration of L-propranolol. A maximum reduction in heart rate of about 20% was seen, but no tolerance was observed. All animals showed, however, rebound effects that were at a maximum 3 days after drug withdrawal. Different PK/PD models have been fitted to the data and an indirect effect model seems to be the most appropriate.
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PMID:Pharmacodynamic aspects of drug administration. Tolerance development. 1083 63

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.
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PMID:Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease. 1118 73

The response to levodopa changes over time in Parkinson's disease, probably due to alterations in the dopaminergic system, progression of the disease and pulsatile oral intake of the drug. Bilateral high-frequency stimulation of the subthalamic nucleus (STN) allows a large reduction or the complete cessation of levodopa intake in patients with advanced Parkinson's disease. We studied variation in the motor short-duration response (SDR) during a levodopa challenge in bilaterally STN-stimulated patients. Twenty-eight consecutive patients with a mean duration of Parkinson's disease of 16.6 +/- 6.0 years at the time of surgery were enrolled. Fourteen patients were evaluated both before STN stimulation and 3 months after surgery (group 1) whereas the other 14 patients were assessed before implantation and after a mean of 3 years of STN stimulation (group 2). After drug withdrawal for one night, the hand-tapping test (TT) was carried out every 15 min, together with evaluation of dyskinesias using a modified Goetz scale. The Unified Parkinson's Disease Rating Scale (UPDRS) motor score was assessed every 30 min. In operated patients, STN stimulation was stopped 15 min before starting the clinical evaluations. A suprathreshold oral levodopa dose was given after one motor evaluation and two TTs. The clinical evaluation was carried out until the TT score returned to the baseline. In group 1, six patients continued without levodopa after surgery and the other eight received a daily mean dose of 337 mg; in group 2, seven patients continued without levodopa and the other seven received a daily mean dose of 386 mg. The main change in the levodopa SDR was a significant reduction in levodopa-induced dyskinesias in both groups. In those patients of group 1 who did not receive levodopa after surgery, the motor UPDRS magnitude decreased and the 'on' UPDRS motor score worsened. In group 2, the results were similar, but in the patients who continued to receive levodopa after surgery the TT magnitude increased. On the whole, chronic bilateral STN stimulation tended to decrease the magnitude of the levodopa SDR without changing the duration and latency of the response. These results suggest that continuous STN stimulation induces long-term plastic changes of the dopaminergic system, with slow and partial desensitization. In addition, the persistence of levodopa intake after surgery might hinder this beneficial process.
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PMID:Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation. 1239 Sep 68


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