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)

Depression is commonly associated with idiopathic Parkinson's disease. Various antidepressants can be helpful in the treatment of this type of depression. Anticholinergic medications are at times used for treating the motor symptoms of parkinsonism. While some authors have reported euphorigenic effects from anticholinergics in other groups of patients, generally, they have not been used in the treatment of depression, with or without parkinsonism. In the case presented, a depressed patient with Parkinson's disease on levodopa/carbidopa and fluoxetine was given benztropine for his motor symptoms. The result was some improvement in his motor symptoms and a wide, dose-related spectrum of other central nervous system changes ranging from delirium to mania, hypomania, and euthymia from a "baseline" of residual depression. At a very low dose (0.25 mg per day), benztropine appeared to have an augmenting antidepressant effect that rendered the patient euthymic.
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PMID:Anticholinergic effects in a depressed parkinsonian patient. 779 71

Hedonistic homeostatic dysregulation is a neuropsychological behavioural disorder associated with substance misuse and addiction. The disorder has been recognised as a consequence of dopamine replacement therapy (DRT) in 15 patients with Parkinson's disease. The syndrome typically develops in male patients with early onset Parkinson's disease, and can occur with orally and subcutaneously administered DRT. These patients take increasing quantities of their DRT, despite increasingly severe drug induced dyskinesias, and may develop a cyclical mood disorder with hypomania or manic psychosis. There is impairment of social and occupational functioning. Tolerance develops to mood elevating effects of DRT and a negative affective withdrawal state occurs if the drugs are withdrawn or doses decreased. The clinical features and guidelines for managing this syndrome are discussed. A set of diagnostic criteria for further investigating this condition is proposed.
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PMID:Hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies. 1118 44

We report a case of recurrent manic episodes associated with chronic deep brain stimulation (DBS) targeting globus pallidus (GP) in the treatment of Parkinson's disease (PD). Cardinal PD symptoms and dyskinesia improved with DBS, and neuropsychological testing found improvements in visuospatial measures associated with left DBS and in verbal memory with right DBS when compared to the patient's preoperative baseline. Under conditions of right, left, and bilateral DBS, the patient experienced bouts of mania and hypomania lasting several days at a time. Positron emission tomography (PET) with (15)O-labeled water was performed after his first manic episode under four conditions: no stimulation, right DBS, left DBS, and bilateral DBS. Although no manic switch occurred during the course of the PET study, all three DBS conditions were associated with decreases in regional flow in the left parahippocampus and hippocampus and right mid-cingulate gyrus. Increases in flow in left inferior frontal area, bilateral insula, dorsolateral prefrontal cortex, and cuneus were common to all DBS conditions. GP stimulation in PD may be associated with behavioral and cognitive effects. Distributed blood flow changes observed with pallidal DBS support a role for the pallidum in cognition and affective regulation.
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PMID:The behavioral complications of pallidal stimulation: a case report. 1075 88

Cognitive and emotional outcomes were assessed after unilateral posteroventral pallidotomy (PVP) and ventral intermediate nucleus thalamotomy (Vim-Th) in patients suffering from idiopathic Parkinson's disease (PD). PVP was performed on 12 PD patients (8 men and 4 women, mean age 56.4 years, 6 left lesions and 6 right lesions) and Vim-Th was performed on 13 PD patients (5 men and 8 women, mean age 63.2 years, 6 left lesions and 7 right lesions). In both the PVP group and the Vim-Th group, the Hoehn and Yahr staging scores (p < 0.01) and the Unified Parkinson's Disease Rating Scale activities of daily living and motor scores (p < 0.001) improved significantly. No significant changes in cognitive function were observed 4 weeks after unilateral PVP or Vim-Th. PVP produced a significant decline in Hasegawa's Dementia Scale-Revised scores in immediate postoperative assessments (p < 0.05), which resolved 4 weeks after surgery. While the Minnesota Multiphasic Personality Inventory depression and social introversion scores improved significantly in the Vim-Th group (p < 0.01 and p < 0.05, respectively), the hypochondriasis and hypomania scores improved significantly in the PVP group (p < 0.01 and p < 0.05, respectively). We conclude that PVP and Vim-Th influence postoperative emotional status rather than postoperative cognitive status.
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PMID:Neuropsychological outcome following pallidotomy and thalamotomy for Parkinson's disease. 1112 60

We report on 6 patients with Parkinson's disease who developed severe repetitive behavior, 2 with pathological gambling and 4 with cleaning, rearranging, and ordering rituals. The onset of repetitive behaviors was not associated with changes in antiparkinsonian medications, the behavior did not improve after reductions in dopaminergic therapy, and thus they seem to be part of the underlying illness. The disabling cleaning/rearranging/ordering behaviors had associated features of hypomania, occurred exclusively during motor on periods, and often occurred nocturnally. The repetitive behavior responded poorly to serotonin reuptake inhibitors. Certain atypical antipsychotics may be of benefit.
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PMID:Disabling repetitive behaviors in Parkinson's disease. 1507 33

This review deals with the range of neuropsychiatric problems that may arise from the use of medical and surgical therapies in the treatment of Parkinson's disease. As new approaches emerge, these problems are diversifying. Well-recognized drug-related complications include hallucinations and psychosis and the so-called dopamine-dysregulation syndrome. The etiology of these problems has not been fully established and is not clearly dose related, while the management can be difficult and needs to be tailored to the individual patient. Cholinergic and dopaminergic drugs may both influence cognitive function. The development of pharmacogenetics could improve the therapeutic ratio of medical approaches to PD in the future. The literature relating to the neuropsychiatric issues complicating the surgical treatment of Parkinson's disease is more recent and frequently suffers from methodological problems, lack of a systematic approach, and adequate patient follow-up. The emergence of neuropsychiatric problems in association with surgery has shed new light upon the pathophysiological mechanisms underpinning these symptoms. Depression, hypomania, euphoria, mirth, and hypersexuality have all been described following deep brain stimulation procedures, although most studies have concentrated upon the depressive features. Anxiety has been described only rarely to date. Fortunately, permanent cognitive complications appear to be rare. The optimal management approach for surgically related neuropsychiatric problems is unknown at present. Prospective multicenter studies would contribute significantly to resolving this therapeutic uncertainty.
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PMID:Neuropsychiatric complications of medical and surgical therapies for Parkinson's disease. 1531 81

In this study we aimed to investigate the effects of bilateral STN HFS in patients with advanced Parkinson disease (PD) at long-term, with a minimum follow-up of 4 years. Twenty patients (15 men, five women) were included, with a mean age of 60.9+/-8.1 years. Surgery was performed under local anesthesia. The target was defined on computerized tomography (CT). At 3 months, significant improvements were found on the total Unified Parkinson disease rating scale (UPDRS) III (motor) score, in the medication. off (from 42.3+/-9.3 to 19.5+/-6.4), as well as the medication on (from 18.6+/-12.1 to 10.1+/-5.9) phase. The UPDRS IVa (dyskinesias) and IVb (motor fluctuations) scores decreased significantly. At long-term follow-up, there were still significant improvements on the total UPDRS III motor score (from 42.3+/-9.3 to 24.2+/-13.2), as well as in all motor subscores, in the off phase, during stimulation. In the on phase, the only significant improvement was seen for rigidity. Complications included hypomania to mania in four patients. Our results indicate that HFS STN results in long-lasting improvement of the motor symptoms, ADL activities and functional performance in patients suffering from advanced PD. The stimulation induced behavioural changes need special consideration.
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PMID:Long-term effects of bilateral subthalamic nucleus stimulation in advanced Parkinson disease: a four year follow-up study. 1582 80

Executive dysfunction (ED) is a prominent and often disabling feature of cognitive impairment in Parkinson's disease (PD). Few studies have examined treatments. Given the role of noradrenergic pathology in ED, atomoxetine, a norepinephrine reuptake inhibitor indicated for attention deficit hyperactivity disorder (ADHD), may be a potential treatment for PD-related ED. Twelve patients with PD and disabling ED completed an 8-week pilot open-label, flexible dose (25-100 mg/day) trial of atomoxetine. On primary outcome measures, atomoxetine was associated with improved ED based on the Clinical Global Impression-Change Scale (75% positive response rate; 95% CI: 43-95%, P < 05) and behavioral measures of ED [Frontal Systems Behavior Scale (FrSBE) Executive Dysfunction and Connors Adult ADHD Rating Scale (CAARS) inattention/memory subscales]. Adverse effects included sleep and gastrointestinal disturbances and hypomania. Atomoxetine is tolerable in PD and may benefit clinical manifestations of ED, warranting further study in controlled trials.
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PMID:Atomoxetine for the treatment of executive dysfunction in Parkinson's disease: a pilot open-label study. 1902 77

Among the basal ganglia nuclei, the subthalamic nucleus has a major function in the motor cortico-basal ganglia-thalamo-cortical circuit and is a target site for neurosurgical treatment such as parkinsonian patients with long-term motor fluctuations and dyskinesia. According to animal and human studies, the motor functions of the subthalamic nucleus have been well documented whereas its implication on limbic functions is still less well understood and is only partially explained by anatomical and functional theories of basal ganglia organisation. After chronic subthalamic nucleus stimulation in patients with Parkinson's disease, many studies showed executive impairments, apathy, depression, hypomania, and impairment of recognition of negative facial emotions. The medial tip of the subthalamic nucleus represents its limbic part. This part receives inputs from the anterior cingulate cortex, the medial prefrontal cortex, the limbic part of the striatum (nucleus accumbens), the ventral tegmental area and the limbic ventral pallidum. The medial tip of the subthalamic nucleus projects to the limbic part of the substantia nigra and the ventral tegmental area. We propose a new function scheme of the limbic system, establishing connections between limbic cortical structures (medial prefrontal cortex, amygdala and hippocampus) and the limbic part of the basal ganglia. This new circuit could be composed of a minor part based on the model of cortico-basal ganglia-thalamo-cortical loop, and of a major part linking the subthalamic nucleus with the mesolimbic dopaminergic pathway via the ventral tegmental area and the nucleus accumbens, and with limbic cortical structures. This scheme could explain limbic impairments after subthalamic nucleus stimulation by disruption of limbic information inside the subthalamic nucleus and the ventral tegmental area.
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PMID:The subthalamic nucleus is a key-structure of limbic basal ganglia functions. 1915 19

Bilateral high-frequency stimulation of the subthalamic nuclei is now considered as the method of choice for the treatment of severe and advanced forms of Parkinson's disease. The technique improves patients' quality of life, disability, motor complications and allows the dose of dopaminergic treatment to be reduced. The dramatic motor benefits provided by the technique were firstly accompanied by a number of psychiatric complications--depression hypomania or mania, anxiety disorders or behavioural disorders--reflecting both the deleterious effect of modulation of the limbic circuit and the (inappropriate) selection of patients with past history of severe psychiatric disorders. Following a number of prospective studies, it is now considered that the rate of severe psychiatric side effects induced by deep brain stimulation is low, provided that the patients are well selected, the electrodes adequately placed and the postoperative follow-up appropriately performed. Interestingly, the favourable effects of the technique on both anxiety disorders (particularly obsessive compulsive disorders) and some behavioural disorders (mainly repetitive behaviour), strongly suggests that deep brain stimulation-associated modulation of associative and limbic circuits--through the basal ganglia--might be the method of choice for the future treatment of severe and medically refractory neuropsychiatric disorders such as Tourette's syndrome, obsessive compulsive disorders and addiction disorders.
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PMID:[Deep brain stimulation, Parkinson's disease and neuropsychiatric complications]. 1923 3


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