GPi pallidotomy for Parkinson's disease with drug-induced psychosis

Levodopa-induced psychosis may seriously threaten the ability of patients with Parkinson's disease (PD) to continue leading an independent life. A retrospective assessment of the therapeutic effects of the globus pallidus internus (GPi) pallidotomy on the activities of daily living (ADL) of seven PD patients presenting with mild or moderate degrees of psychosis was carried out. Their scores according to the Unified Parkinson's Disease Rating Scale (UPDRS) Part I-2 (maximum=4) were 2 or 3 (mean +/- SD=2.4 +/- 0.5). Bilateral procedure was needed in 5 out of 7 patients to obtain sufficient improvement of motor symptoms. At 3 months after surgery, UPDRS part III motor scores in the 'off' state were significantly decreased and motor fluctuations were abolished. Nevertheless, their score of Schwab and England (S-E) ADL scale scores responded poorly to the surgery, while the scores in other 12 patients without psychosis was significantly improved after pallidotomy. The data indicate that GPi pallidotomy ameliorates the motor symptoms in patients with drug-induced psychosis (DIP), but has no significant impact on their consequent daily activities. A regression model for all 19 patients who underwent pallidotomy revealed that postoperative S-E scale was affected by the preoperative UPDRS Part I-2 rather than by Part III motor score. The present study suggested that DIP, even if its degree is not severe, may be a limiting factor of the therapeutic potential of pallidotomy in patients with PD.     

Quetiapine for the treatment of drug-induced psychosis in Parkinson's disease.

Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.     

Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study

The effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intracally intractable Parkinson's disease(PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug-induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3-month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined “on/off” Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1-year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.     

Postero-ventral pallidotomy in Parkinson's disease

Fetal graft research and renewed interest in Leksell's postero-ventral pallidotomy (PVP) stimulated reconsideration of surgical therapy for Parkinson's disease (PD), particularly with regard to improving akinetic symptoms previously thought resistant to surgical lesions. A review of our series and other published results of PVP and fetal grafts, show that PVP has beneficial effects on both akinetic and hyperkinetic symptoms that exceed the results reported for fetal graft implantation and other conventional stereotactics. Using the Unified Parkinson's Disease Rating Scale (UPDRS) for pre- and postoperative evaluation of 113 P-V pallidotomies, we found that PVP gave significant reductions in total UPDRS scores, as well as hyperkinetic and akinetic motor scores, dyskinesias, and 'off' periods (P相似文献   

Hypersexuality after right pallidotomy for Parkinson's disease

The authors describe hypersexuality following atypical right pallidotomy for intractable Parkinson's Disease (PD). This patient and literature review suggest important roles for the pallidum in sexual behavior and dopamine in sexual arousal.     

Effect of quetiapine fumarate on drug-induced psychosis in patients with Parkinson's disease]

Among atypical antipsychotics, quetiapine is characterized by a lower incidence of aggravation of parkinsonism due to its lower affinity to D 2. In this study, the effect of quetiapine fumarate (quetiapine) on antiparkinsonian-drug-induced psychosis (e.g. hallucination and delusion) in patients with Parkinson's disease was examined. Ten patients with antiparkinsonian-drugs-induced psychosis were enrolled in this study. The average age of the patients was 69 years and the mean duration of illness was 7 years and 5 months. Psychosis and parkinsonism in these patients were assessed by the Japanese version of PANSS (Positive and Negative Symptom Scale) and UPDRS (Unified Parkinson's Disease Rating Scale) before and during administration of quetiapine, respectively. During the assessment of the effect of quetiapine, the antiparkinsonian drugs that the patients were taking were unchanged. In nine out of the 10 patients, psychotic symptoms disappeared following administration of a relative small dose of quetiapine. No remarkable aggravation of parkinsonism was observed. The present results indicate that quetiapine is an useful drug for treating antiparkinsonian-drug-induced psychosis in the patient with Parkinson's disease.     

Treatment of advanced Parkinson's disease by unilateral posterior GPi pallidotomy: 4-year results of a pilot study.

To assess the long-term outcome following unilateral pallidotomy for advanced Parkinson's disease, we performed nonblinded Core Assessment Program for Intracerebral Transplantations protocol assessments in 10 of the original 15 patients in our pilot study for 4 years following surgery. Although Unified Parkinson's Disease Rating Scale motor examination scores returned to baseline levels at 3 and 4 years, most patients continued to show sustained improvements in contralateral tremor, akinesia, and drug-induced dyskinesias. Contralateral tremor was absent at 4 years in all seven patients with preoperative tremor. Contralateral "off" arm movement times (averaged for three tasks) decreased by 37% at 1 year and by 30% at 4 years. Contralateral dyskinesia scores improved by 82% at 1 year and by 64% at 4 years. In contrast, after reaching speeds equal to the contralateral side at 1 year, ipsilateral "off" movement times increased by 13% over baseline levels at 4 years. Although most gait and postural stability measures showed modest initial improvement followed by a return to baseline values, "on" stand-walk-sit task performance declined significantly at 4 years. Despite the restriction of our surgeries to one side and the expected natural progression of Parkinson's disease, the results of patient self-assessments suggest that 4 years after unilateral pallidotomy, most patients continue to experience a quality of life above preoperative levels.     

Cognitive functioning after pallidotomy for refractory Parkinson's disease

BACKGROUND—Earlierapproaches to pallidotomy for refractory Parkinson's disease hadsignificant complication rates. More recent approaches show fewercomplications, but the effect of pallidotomy on cognition is unclear.The current study was conducted to examine the neuropsychological effects of unilateral pallidotomy.
METHODS—Neuropsychologicaltesting was performed on patients with medically refractory,predominantly unilateral Parkinson's disease at baseline andafter unilateral ventral pallidotomy (n=28)or after an equivalent period withoutsurgery in control patients (n=10).
RESULTS—Pallidotomypatients showed no significant changes from baseline to retestingrelative to the control group for any measure. Across all of the testsadministered, only five of the surgery patients showed a significantdecline, and of these five none declined on more than one test.Depression did not relate to preoperative or postoperative cognition.The pallidotomy group showed a significant improvement in motorfunctioning and activities of daily living whereas the control groupdid not. These measures were not associated with the neuropsychologicaltest scores at baseline or retest.
CONCLUSIONS—Stereotacticunilateral ventral pallidotomy does not seem to produce dramaticcognitive declines in most patients.

     

Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease.

Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS     

微电极导向同期行丘脑及苍白球腹后部毁损治疗帕金森病

对震颤、僵硬及运动迟缓帕金森病患者的立体定向手术法进行探讨。方法应用微电极导向技术,对８６例ＰＤ患者行同侧丘脑腹外则核及苍白求腹后部同期毁损手术。结果８６例ＰＤ患者的肢体震颤、僵硬及运动迟缓均得到明显改善,术前术后ＭｏｔｏｒＵＰＤＲＳ积分开状态及关状态均有显著提高,无永主并发症。     

Unilateral pallidotomy for Parkinson's disease disrupts ocular fixation.

Although some motor functions of the basal ganglia have been well studied, the oculomotor functions are not well established. We studied eye movements in patients with Parkinson's disease (PD) undergoing pallidotomy to assess the role of the globus pallidus interna (GPi) in oculomotor control. Horizontal visually guided, gap and predictive saccades as well as ocular fixation were studied in patients with advanced PD before and 1 month after unilateral pallidotomy, and in healthy controls on two occasions 1 month apart. There was no difference in saccadic latency or accuracy, the number of saccadic anticipations or the ability to generate predictive saccades between the two assessments for either patients or controls. The number and amplitude of square wave jerks during ocular fixation however increased significantly in patients after pallidotomy. The results imply altered function of frontal or prefrontal cortical regions involved in ocular fixation resulting from a disruption to inhibitory pallidal influences on thalamocortical projections. The posteroventral GPi however appears not to be involved in externally controlled or predictive saccadic function.     

Clozapine for psychosis in Parkinson's disease

The clinical efficacy of clozapine, an atypical antipsychotic, in treating levodopa-induced hallucinations was investigated in five patients with Parkinson's disease under open label conditions. Two patients could not tolerate clozapine, even in doses as low as 12.5-25 mg daily, because of extreme sedation. Three patients could tolerate clozapine and experienced improvement or elimination of their hallucinations at doses below 100 mg daily. Despite a significant risk of adverse effects, cautious use of clozapine in low doses may be beneficial for patients with levodopa-induced psychosis who do not respond to more conservative measures.     

Randomized trial of pallidotomy versus medical therapy for Parkinson's disease

Thirty-six patients with Parkinson's disease (PD) were randomized to either medical therapy (N = 18) or unilateral GPi pallidotomy (N = 18). The primary outcome variable was the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow-up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug-induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug-induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS (p < 0.0001), "off" motor (p < 0.0001) and complications of therapy subscores (p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug-induced dyskinesias.