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.     

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.     

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.     

Unilateral pallidotomy in advanced Parkinson's disease: a retrospective study of 26 patients.

OBJECTIVE: To evaluate the effects of unilateral pallidotomy in patients with Parkinson's disease (PD). PATIENTS AND METHODS: Twenty-six patients with PD and disabling dyskinesias, painful and/or disabling dystonia, and/or pain as part of PD despite optimal pharmacotherapy underwent unilateral pallidotomy. For assessment, the Unified Parkinson's Disease Rating Scale (UPDRS; part II and III), Hoehn and Yahr staging, the Schwab and England scale, a Dyskinesia Rating Scale, and timed tests were used. Assessment was performed in defined "off' and "on," and on average 2 months before and 7.5 months after the unilateral pallidotomy. Adverse effects were classified as transient or permanent and as major or minor. RESULTS: In the "off' phase, the median UPDRS II score improved from 26.5 to 20.5 (23%) and the median UPDRS III score improved from 47.5 to 33.0 (31%). In the "on" phase, dyskinesias contralateral to the side of the procedure improved with 88% ipsilateral dyskinesias improved only temporarily, and the total UPDRS II and III scores remained unchanged. Thirteen patients had transient adverse effects, three patients had permanent, and two patients had a combination of transient and permanent adverse effects. The transient adverse effects in two patients were classified as major. CONCLUSION: Stereotactic unilateral pallidotomy can improve symptoms and disability in the "off' phase. In the "on" phase, dyskinesias disappeared at the side contralateral to the procedure. Permanent minor complications of pallidotomy occurred in 19% of the patients.     

Treatment of advanced Parkinson's disease by subthalamotomy: one-year results.

We studied effects on parkinsonian features at 6 and 12 months in 12 patients who underwent unilateral ablation of subthalamic nucleus (STN). Microelectrode mapping was used, and a lesion was created in the STN using thermal coagulation and confirmed with magnetic resonance imaging. At 6 months postoperatively, improvements were seen in several areas: 1) Unified Parkinson's Disease Rating Scales II and III (UPDRS II and III) scores, 30% in off period, 38% in on period; 2) Schwab and England Scale (S&E) score, 21%; and 3) on dyskinesia, 85%. Contralateral rigidity, bradykinesia, UPDRS II and III scores, and S&E scores remained improved at 12 months. Daily dosage of levodopa requirement was reduced by 42%. Axial motor features, gait, postural stability, off period tremor, and motor fluctuation improved at 6 and 12 months but showed a decline in benefits at 18 months. Complications include 3 cases of hemiballism, of whom 2 patients recovered spontaneously but 1 died from aspiration pneumonia. One patient had asymptomatic hematoma, and 2 suffered transient postural asymmetries. We conclude that unilateral subthalamotomy results in moderate improvement in all aspects of parkinsonian features, allows reduction in the dose of levodopa required, and ameliorates drug-induced complications throughout 12-month assessments.     

Usefulness of pallidotomy in advanced Parkinson's disease.

OBJECTIVE: The combined effect of posteroventral pallidotomy and optimal medical treatment was assessed in 22 patients with levodopa sensitive Parkinson's disease. METHODS: Timed motor tests, video recordings, and computer assisted optoelectronic movement analysis were used for serial hourly assessments performed preoperatively and four and 12 months after operation. Tests were made while patients were on optimal medical therapy. RESULTS: There were no serious adverse events of surgery. Two of the 22 patients could not complete all the tests after operation. The proportion of dyskinesia periods decreased in the 20 patients and there was a proportional increase in normal or fairly normal occasions. "Off" periods were not significantly affected. In 12 of 13 patients with limb dyskinesia this symptom was completely abolished in the contralateral limbs. There was also some degree of improvement axially and ipsilaterally. Tremor was moderately improved contralaterally. Bradykinesia remained unchanged. Results at 12 months follow up were similar to those at four months. CONCLUSION: Pallidotomy produced a pronounced positive effect on dyskinesia and a moderate effect on tremor. Bradykinesia was not affected. Posteroventral pallidotomy may be useful in patients with Parkinson's disease who have severe motor fluctuations and may allow an increase in levodopa dose to alleviate bradykinesia in "off" states.     

Four year follow-up study after unilateral pallidotomy in advanced Parkinson's disease

BACKGROUND: Pallidotomy is widely accepted as a treatment for patients with Parkinson's disease (PD) who have disabling symptoms that are inadequately controlled with pharmacotherapy. There are, however, only a few studies, with a small number of patients, showing evidence after prolonged periods of time about the clinical outcome after pallidotomy. METHODS: We have conducted a four-year follow-up study of 23 patients with PD who had undergone unilateral pallidotomy. Six patients were lost to follow-up. The remaining 17 were evaluated before surgery and at three months, one year, and four years after surgery, following standard protocols. RESULTS: At four years, patients still showed significant amelioration in contralateral and axial dyskinesias and off-period contralateral parkinsonian signs. Total motor UPDRS and Activities of Daily Living scores also remained improved four years after surgery. Ipsilateral and axial parkinsonian symptoms and Hoehn & Yahr and Schwab & England scales were not significantly changed from baseline values. The initial beneficial effects on motor fluctuations were not maintained at last visit. All patients considered themselves to be improved with respect to their clinical condition before surgery in a clinical global impression estimation done at the four-year follow-up. CONCLUSION: Unilateral pallidotomy can provide sustained improvement of contralateral parkinsonism and dyskinesias during at least four years. Early benefits observed in axial symptoms and motor fluctuations wane with time. On period akinesia worsened significantly in the limbs contralateral to pallidotomy after four years.     

Outcome of unilateral pallidotomy in advanced Parkinson's disease: cohort study of 32 patients

OBJECTIVES: In a randomised trial to study the efficacy of unilateral pallidotomy in patients with advanced Parkinson's disease, patients having pallidotomy within 1 month after randomisation were compared with patients having pallidotomy 6 months after the primary outcome assessment. Of the 37 patients enrolled 32 had a unilateral pallidotomy. The follow up study of these patients is presented to report (1) clinical outcome; (2) adverse effects; (3) cognitive and behavioural effects; (4) relation between lesion location and outcome; and (5) preoperative patient characteristics predictive for good outcome. METHODS: Outcome measures were the motor section of the unified Parkinson's disease rating scale (UPDRS), levodopa induced dyskinesias, disability, quality of life, and a comprehensive neuropsychological assessment. Multivariate logistic regression was used to identify preoperative patient characteristics independently associated with good outcome. RESULTS: Off phase assessment showed a reduction in parkinsonism from 49 to 36.5 points on the UPDRS 6 months after surgery. Improvements were also demonstrated for activities of daily living and quality of life. In the on phase dyskinesias were reduced. All effects lasted up to 12 months after surgery. Three patients had major permanent adverse effects. Besides worsening of verbal fluency after left sided surgery, systematic cognitive deterioration was not detected. Patients taking less than 1000 levodopa equivalent units (LEU)/day were more likely to improve. CONCLUSIONS: The positive effects of unilateral pallidotomy are stable up to 1 year after surgery. Patients taking less than 1000 LEU per day were most likely to improve.     

Bilateral pallidotomy in Parkinson's disease: a retrospective study.

We evaluated the effects of bilateral pallidotomy in patients with advanced Parkinson's disease. Thirteen patients with Parkinson's disease had a staged bilateral pallidotomy if they had severe response fluctuations, dyskinesias, painful dystonia, or bradykinesia despite optimum pharmacological treatment. Assessment scales were the Unified Parkinson's Disease Rating scale (UPDRS), the Schwab and England scale, and a questionnaire on the effects of disability in activities of daily living and adverse effects. Postoperative magnetic resonance imaging was evaluated for lesion location and extension. The median off-phase UPDRS motor score was reduced from 43.5 to 29 after the first pallidotomy, and it was further reduced to 23.5 after the second pallidotomy (n = 8). The UPDRS activities of daily living off-phase score improved from 28.5 to 20.5 after the first pallidotomy and to 19 after the second pallidotomy (n = 6). The Schwab and England scale off-phase score showed an improvement after both procedures, first from 40 to 60, and thereafter to 90 (n = 8). On-phase dyskinesias were reduced substantially. Eight patients had adverse effects, of whom five had problems with speech. One patient became hemiplegic due to a delayed infarction. Ten patients experienced further benefit from the second procedure. Bilateral pallidotomy reduces dyskinesias. A second contralateral pallidotomy may reduce parkinsonism, although to a lesser degree compared with the first pallidotomy and with an increased risk for adverse effects.     

Outcomes following staged bilateral pallidotomy in advanced Parkinson's disease

The authors assessed clinical outcome for up to one year after staged bilateral pallidotomy in 14 patients with advanced PD. One year after surgery, dyskinesias were virtually abolished and there were significant reductions in "off" time (67%) and activities of daily living "off" scores (24%), as well as nonsignificant reduction in "off" motor score (39%); "on" scores were unchanged. One patient developed a visual field deficit; two had transient confusion. Staged bilateral pallidotomy improves motor function in selected patients with advanced PD.     

Efficacy and safety of simultaneous bilateral pallidotomy in advanced Parkinson's disease

BACKGROUND: Although unilateral pallidotomy is generally considered a safe and effective neurosurgical treatment for advanced Parkinson's disease (PD), controversies concerning efficacy and adverse effects of bilateral posteroventral pallidotomy (PVP) exist and need to be resolved. METHODS: We studied 8 patients with advanced PD who underwent simultaneous bilateral PVP. The patients were assessed preoperatively, immediately after surgery, and 6 and 12 months later. RESULTS: Dyskinesia was almost entirely abolished immediately after surgery, as well as being significantly lower 1 year later (p < 0.05). The 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) was significantly improved after surgery (p < 0.05) but increased gradually after 6 months. The off medication score of activities of daily living tended to improve immediately after surgery, but it returned to preoperative levels at 12 months. There were no major complications of surgery. CONCLUSIONS: Simultaneous bilateral PVP may be a safe and highly effective method of reducing levodopa-induced dyskinesia. Our results suggest that simultaneous bilateral PVP may be a reasonable therapeutic option for advanced PD with severe levodopa-induced dyskinesia.     

Mood changes with deep brain stimulation of STN and GPi: results of a pilot study

The results of this study suggest that there are mood changes associated with deep brain stimulation of the subthalamic nucleus (STN) and the globus pallidus interna (GPi). Further, optimal placement of electrodes in both STN and GPi seems to result in overall improvement in mood and is associated with a lower incidence of adverse mood effects than stimulation outside the optimal site. Preliminary data from this study, however, suggest that slight movement dorsal or ventral to the site of optimal motor performance may be associated with more adverse changes in mood with STN stimulation than with GPi stimulation.     

Treatment of depression in Parkinson's disease with moclobemide: A pilot open-label study

Moclobemide, a potent reversible monoamine-oxidase A (MAO-A) inhibitor, is an effective antidepressant that does not cause impairment of cognitive function in elderly patients and might be beneficial to motor deficits in Parkinson's disease (PD). In a 12-week open-label prospective study, we administered moclobemide (300–600 mg day⁻¹) as an add-on medication to twelve PD patients who met DSM-III-R criteria for depressive illness. There were two early drop-outs due to subjective worsening of Parkinsonism associated with insomnia and anorexia, respectively. The Beck Depression Inventory score decreased significantly in the ten patients who completed the study, and clinical global assessment of efficacy recorded ‘good’ or ‘excellent’ responses or in nine of the ten patients. Mean parkinsonian disability, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab-England Daily Life Activities scales, remained unchanged throughout the study in the group as a whole. However, worsening or onset of resting tremor occurred in five patients and the UPDRS tremor subscore in the group overall was significantly higher by week 8 (p = 0.03) when dose titration was optimal. There was a trend toward improvement in UPDRS bradykinesia subscores that did not attain statistical significance. Compared to baseline, patients complained more often of insomnia, anorexia, increased perspiration, and restlessness. Though these preliminary results need to be replicated in a large controlled trial, we suggest that moclobemide may be an effective alternative in the treatment of PD associated depression.     

Stereotactic posteroventral pallidotomy: clinical methods and results at 1-year follow up.

Twenty consecutive patients with idiopathic Parkinson's disease underwent stereotactic posteroventral pallidotomy. Schwab and England ADL scores in the "off" state were improved by 18% and in the "on" state the scores declined by 2%. Three patients also reported marked improvement in "off" state dystonia. One-year data are available on 12 patients who underwent evaluations according to the Core Assessment Program for Intracerebral Transplantation protocol preoperatively and at 3, 6, and 12 months after surgery. Significant improvements in Unified Parkinson's Disease Rating Scale sections II and III scores in the "off" state, composite "off" state scores of bradykinesia and rigidity, contralateral tremor in the "off" state, and contralateral dyskinesias were observed. Although there was reduction in the daily levodopa dose, this did not reach statistical significance. Major complications (15%) included hemiparesis (one of 20) and visual field cuts (two of 20); minor complications (45%) included mild cognitive dysfunction (four of 20), reading difficulty not related to visual disturbance (one of 20), and 5-10 lb weight gain (four of 20).     

Ethosuximide and tremor in Parkinson's disease: a pilot study.

Following the demonstration of an anti-tremor effect of ethosuximide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model, we have tested the effect of this drug in 10 patients with typical parkinsonian tremor. Six patients suffered from Parkinson's disease with prominent, relatively drug-resistant rest tremor. The other four patients had a drug-induced parkinsonian tremor due to neuroleptic agents taken for a psychiatric condition. Five of the six parkinsonian patients and three of the four psychiatric patients reported within a few days a marked and intolerable exacerbation of their tremor. One patient in each group was improved, and this improvement was verified in repeated examinations. Thus, for unknown reasons, the effect of ethosuximide was not as predicted by the monkey model. Among possible explanations is the fact that we had chosen patients with drug-resistant tremor.     

Testosterone deficiency and apathy in Parkinson's disease: a pilot study

BACKGROUND: Low testosterone in men with Parkinson's disease may be associated with non-motor symptoms of the disease, such as apathy. OBJECTIVE: To determine the association between free serum testosterone level and apathy in elderly men with Parkinson's disease. METHODS: Consecutive non-demented patients (n = 49) and knowledgeable informants (n = 40) participated in the study. Patients and informants reported on apathy using the Frontal Systems Behavior Scale and two visual analogue scales. Patients also provided self reported symptoms of depression on the Beck depression inventory-II. Blood samples were drawn at the time of assessment to determine testosterone levels. RESULTS: A low total testosterone concentration was found in 46.9% of the patients, defined as < or = 325 ng/dl. Free testosterone was significantly correlated with both patient reported and informant reported apathy, independent of disease severity. CONCLUSIONS: Apathy is common in Parkinson's disease and is inversely correlated with free testosterone. Testosterone replacement therapy could be considered as a potential treatment for apathy in some men with Parkinson's disease. More research is needed to replicate these findings and to investigate the response to treatment.     

Bright light therapy in Parkinson's disease: a pilot study.

Several observations suggest a beneficial effect of melatonin antagonism for Parkinson's disease (PD). Although bright light therapy (BLT) suppresses melatonin release and is an established treatment for depression and sleep disturbances, it has not been evaluated in PD. We examined effects of BLT on motor symptoms, depression, and sleep in PD in a randomized placebo-controlled double-blind study in 36 PD patients, using Parkinson's Disease Rating Scale (UPDRS) I-IV, Beck's Depression Inventory, and Epworth Sleepiness Scale. All patients received BLT for 15 days in the morning, 30 min daily. Illuminance was 7.500 lux in the active treatment group and 950 lux in the placebo group. Although group differences were small, BLT led to significant improvement of tremor, UPDRS I, II, and IV, and depression in the active treatment group but not in the placebo group. It was very well tolerated. Follow up studies in more advanced patient populations employing longer treatment durations are warranted.