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PubMed2000

Unilateral pallidotomy in PD: a controlled study of cognitive and behavioral effects. The Netherlands Pallidotomy Study (NEPAS) group.

OBJECTIVE: To investigate whether unilateral pallidotomy affects cognitive and behavioral functioning. METHODS: At baseline and after 6 months we assessed neuropsychological functioning in 35 patients with advanced PD. After baseline examination, patients were randomized to pallidotomy within 1 month (6 left-sided, 13 right-sided) or to pallidotomy after follow-up assessment 6 months later (n = 16; control group). We performed neuropsychological tests of language, visuospatial function, memory, attention, and executive functions. Self ratings and proxy ratings of memory problems and dysexecutive symptoms were also collected. RESULTS: No significant differences over time were found between pallidotomy and control groups, with the exception of a decrease of verbal fluency in the left-sided pallidotomy group. CONCLUSIONS: Unilateral pallidotomy is relatively safe with respect to cognition and behavior. Left-sided pallidotomy may lead to minor deterioration in verbal fluency. The sample size of this study is too small, however, to rule out the possibility of infrequent but clinically important side effects.

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PubMed1998

Use of posteroventral pallidotomy for treatment of Parkinson's disease: is pallidotomy still an experimental procedure? A review and commentary.

Surgical interventions have been employed to alleviate symptoms of Parkinson's disease (PD) for decades, with improving success. One such treatment has been pallidotomy, the lesioning of a portion of the globus pallidus. Early pallidotomy procedures have paved the way for more accurately targeted methods. Technological advancements in imaging and targeting have made modern pallidotomy a safe and well-tested means of treating PD patients that has reliably positive results. Numerous group studies in recent years have demonstrated effective relief of PD symptoms, and the neuroanatomical and physiological aspects which underlie its effects are being elucidated as well. Recent descriptions of pallidotomy as an experimental procedure must therefore be considered in light of these reports. This review will examine the development of the pallidotomy procedure and the neuroanatomical rationale which underlies it, and discuss recent studies of its efficacy in PD patients.

Basal Ganglia↗
PubMed1999

Comparison of 1-year follow-up evaluations of patients with indication for pallidotomy who did not undergo surgery versus patients with Parkinson's disease who did undergo pallidotomy: a case control study.

UNLABELLED: Many reports published during the past 5 years have shown evidence of the beneficial effect of posteroventral pallidotomy (PVP) in large groups of patients for up to 3 years, but none of them have compared patients who underwent surgery with a control group. OBJECTIVE: To compare the evolution of Parkinson's disease symptoms at 1-year follow-up between patients who underwent surgery and those who did not. MATERIAL AND METHODS: Ten patients with idiopathic Parkinson's disease refractory to treatment who were included in the Core Assessment for Intracerebral Transplantation program for PVP did not undergo surgery because financial support was lacking. These patients were followed up for 1 year as if they had been operated on and were finally compared with 10 patients having similar characteristics in whom PVP had been performed during the same period of time. RESULTS: There were no significant differences at basal evaluation in the motor section scores of the Unified Parkinson's Disease Rating Scale between those patients who underwent surgery and those who did not, but a significant reduction in Unified Parkinson's Disease Rating Scale motor score in the group who underwent surgery at 1-year evaluation was found (P < 0.006). Dyskinesias, which was nonsignificantly different at basal evaluation, showed, at the 1-year follow-up, a significant reduction in the group who underwent surgery (P < 0.04). Scores from the subsets of the Unified Parkinson's Disease Rating Scale addressing rigidity, tremor, and bradykinesia also proved significantly different at the 1-year follow-up. The slope of the line generated by the two evaluations for each group showed a negative value in the group who underwent surgery (value of -0.21) and a positive value in the group who did not (value of 0.148). CONCLUSION: At the 1-year follow-up, microelectrode-guided PVP produced significant changes in patient motor status and disease progression versus a comparable group of patients who did not undergo surgery during the same period of time.

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PubMed1997

Pallidotomy revisited. Analysis of posteroventral pallidotomy.

Posteroventral pallidotomy (PVP) has been shown to alleviate motor symptoms in Parkinson's disease (PD), e.g., rigidity, secondary akinesia due to existence of muscle rigidity and slight tremor, but not the marked tremor. For the latter, additional lesion of the ventral intermediate nucleus of the thalamus is necessary. Akinesia was divided into three subtypes, and the influence of PVP on each type is described. Primary akinesia is not changed by either PVP or thalamotomy but responds well to L-dopa. Psychological symptoms, i.e., depressive mood, loss of initiation or abulia, and lowered emotional activity, which are generally termed as bradyphrenia, benefit well from PVP but less from thalamotomy. This effect is interpreted as due to the lesion extending into the ventral pallidum, where a small posterior part of the limbic-motor projections may possibly be involved. Such experience suggests that the third type of akinesia in PD, named the 'psychomotor or limbic-motor type' by the author, can be improved by the surgical procedure on the ventral globus pallidus. These observations offer an important chance to understand the psychological symptoms in PD as a result of dopamine deficiency of ventral tegmental area neurons projecting to the ventral striatum, which further influences the ventral pallidum.

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PubMed1997

[Parkinson's disease: from pallidotomy to L-dopa and back to pallidotomy].

Until the introduction of L-dopa in the therapeutics of idiopathic Parkinson's disease (IPD) at the end of the 60's, treatment was essentially limited to anticholinergic drugs and surgical procedures devised to produce discrete lesions in the pallidum, ansa lenticularis and thalamus. L-dopa, associated with dopa decarboxylase inhibitors and dopaminergic agonists, gave rise to an almost complete standstill of surgical procedures. Nevertheless, natural progression of IPD with motor fluctuations and the appearance of L-dopa related abnormal involuntary movements caused surgery to reappear as a primary treatment option. The MPTP epidemic in heroin addicts was responsible for obtaining an experimental model of IPD and became the starting point for a wealth of information concerning the physiopathology of basal ganglia circuitry, neurotransmitters and specific dopaminergic, gabaergic and glutamaergic receptor subtypes involved in motor control. This information, in the context of new stereotactic techniques with modern neuroimaging, enabled old surgical procedures on the internal globus pallidus (Gpi) and thalamus to be reformulated. Additional neurophysiological guidance further improved accuracy in target finding thereby giving rise to impressive results in the symptomatic improvement of IPD including L-dopa induced dyskinesias.

Antiparkinson Agents↗
PubMed2000

Outcome of unilateral and bilateral pallidotomy for Parkinson's disease: patient assessment.

OBJECTIVE: Pallidotomy has recently regained acceptance as a safe and effective treatment for Parkinson's disease symptoms. The goal of this study was to obtain the patients' perspective on their results after undergoing this procedure. Special attention was focused on the potential complications and the respective advantages and risks of unilateral versus bilateral pallidotomy. METHODS: Fifty-six patients were studied during a 2-year period; 44 completed the evaluation, with a median follow-up of 7 months. Of these patients, 22 underwent unilateral pallidotomy, and 17 had bilateral simultaneous pallidotomy. Five patients who underwent staged bilateral pallidotomy were excluded from the statistical analysis, because the number of patients was considered too small for analysis. The procedures were performed with magnetic resonance imaging determination of the target, combined with physiological confirmation, including microelectrode recording. RESULTS: According to Visual Analog Scale scores, unilateral pallidotomy significantly improved dyskinesias (P < 0.05) but no other symptoms. Simultaneous bilateral pallidotomy improved slowness, rigidity, tremor, and dyskinesias (P < 0.05) but worsened speech function (P < 0.05). According to the patients' most frequently chosen answers to multiple-choice questions, unilateral pallidotomy improved night sleep, muscle pain, freezing, overall "on," overall "off," and the duration of "off periods," but it worsened the volume of the voice and articulation, increased drooling, and reduced concentration. Bilateral pallidotomy improved night sleep, muscle pain, freezing, overall "on," overall "off," duration of "off periods," and the amount of medication taken, but it increased drooling and worsened the volume of the voice, articulation, and writing. Subjective visual disturbance was noted in 36 and 41% of patients who underwent unilateral and simultaneous bilateral pallidotomy, respectively. Globally, the result of the procedure was rated "good" or "excellent" by 64% of the patients who underwent unilateral pallidotomy and by 76% of the patients who underwent bilateral pallidotomy. An age less than 70 years was a positive prognostic factor for the global outcome (P < 0.05), as were severe preoperative dyskinesias (P < 0.05). CONCLUSION: This study confirms that, from a patient standpoint, unilateral and simultaneous bilateral pallidotomy can reduce all the key symptoms of Parkinson's disease (i.e., akinesia, tremor, and rigidity) and the side effects of L-dopa treatment (i.e., dyskinesias). Preoperative severe dyskinesias and younger age are positive prognostic factors for a successful outcome. Simultaneous bilateral pallidotomy was more effective than unilateral pallidotomy regarding tremor, rigidity, and dyskinesias, but it conferred a higher risk of postoperative speech deterioration.

Activities of Daily Living↗
PubMed1999

Reassessment of unilateral pallidotomy in Parkinson's disease. A 2-year follow-up study.

Unilateral pallidotomy has gained popularity in treating the motor symptoms of Parkinson's disease. We present the results of a 2-year post-pallidotomy follow-up study. Using the Unified Parkinson's Disease Rating Scale (UPDRS), the Goetz dyskinesia scale and the Purdue Pegboard Test (PPBT), we evaluated 20 patients at regular intervals both off and on medications for 2 years post-pallidotomy. There were no significant changes in the dosages of antiparkinsonian medications from 3 months pre-pallidotomy to 2 years post-pallidotomy. On the side contralateral to the operation, the improvements were preserved in 'on'-state dyskinesia (83% reduction from pre-pallidotomy to 2 years post-pallidotomy, P < 0.001) and 'off'-state tremor (90% reduction from pre-pallidotomy to 2 years post-pallidotomy, P = 0.005). There were no statistically significant differences between pre-pallidotomy scores and those at 2 years post-pallidotomy in ipsilateral dyskinesia, axial dyskinesia, 'off'- or 'on'-state PPBT, 'off'-state Activities of Daily Living (ADL) and 'off'-state gait and postural stability. After 2 years, the 'on'-state ADL scores worsened by 75%, compared with pre-pallidotomy (P = 0.005). We conclude that 2 years after pallidotomy, the improvements in dyskinesia and tremor on the side contralateral to pallidotomy are preserved, while the initial improvements in most other deficits disappear, either because of progression of pathology or loss of the early efficacy achieved by surgery.

Aged↗
PubMed2003

Analysis of complications of radiofrequency pallidotomy.

OBJECTIVE: To systematically report the complications of pallidotomy and to tentatively determine the incidences of complications of pallidotomy, possible influencing factors, and the acceptability of symptomatic hemorrhage rates for microelectrode-guided pallidotomy. METHODS: Clinical events were analyzed for 1116 patients with Parkinson's disease who underwent microelectrode-guided pallidotomies at our center. Complications included visual field deficits, weakness, fatigue, hypersomnia, drooling, dysphagia, speech disorders, hiccups, hemorrhage, seizures, apraxia, coma, infection, mental confusion, and impaired memory. Complication rates for bilateral pallidotomy and double-lesion groups were compared with those for unilateral pallidotomy and single-lesion groups, respectively. RESULTS: Among the total of 1116 patients, the incidences of visual field deficits, weakness, fatigue, hypersomnia, drooling, dysphagia, and speech disorders were 0.4, 4.2, 19.9, 12.4, 7.0, 3.7, and 11.9%, respectively. Symptomatic hemorrhage was observed for 17 patients, apraxia for 3 patients, coma for 2 patients, mental confusion for 24 patients, and impaired memory for 18 of the 1116 patients. The incidences of fatigue, speech disorders, drooling, dysphagia, and hypersomnia were 18.1, 10.3, 5.2, 2.4, and 11.6%, respectively, in the unilateral pallidotomy group and 34.9, 25.5, 22.6, 14.2, and 17.0%, respectively, in the staged pallidotomy group. Of the three patients who underwent simultaneous bilateral pallidotomies (all <50 yr of age), all developed severe fatigue and two exhibited drooling and dysphagia. The incidences of weakness, fatigue, speech disorders, drooling, dysphagia, and hypersomnia were 8.7, 30.4, 18.8, 7.2, 2.9, and 20.3%, respectively, in the double-lesion group and 3.2, 17.2, 9.7, 5.0, 2.3, and 11.5%, respectively, in the single-lesion group. CONCLUSION: Staged bilateral pallidotomy should be carefully evaluated before decision-making, whereas simultaneous bilateral pallidotomy is undesirable. Our study suggests that the size of the final lesion should be limited, to minimize the risks of complications. The incidence of symptomatic hemorrhage in microelectrode-guided pallidotomy is low and acceptable, because of the benefits of microelectrode-guided pallidotomy.

Adult↗
PubMed2002

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.

Data Collection↗
PubMed2003

Effects of pallidotomy and levodopa on walking and reaching movements in Parkinson's disease.

We examined the effects of levodopa and unilateral pallidotomy on quantitative measures of walking and reaching in Parkinson's disease (PD). We also compared quantitative measures of movement with standard clinical rating scales. We used kinematic measures and the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale (subscale III) to evaluate the movement of 10 people with PD. Subjects were tested after withholding PD medications for at least 8 hours and again 30 to 45 minutes after taking the first morning dose of levodopa. They were studied in this manner before unilateral pallidotomy and then 3.5 to 10 months after surgery. The UPDRS motor subscale was performed in each state. Kinematic data were collected as subjects reached to a target and walked. The UPDRS motor subscale ratings were similar to those reported in the literature: pallidotomy improved the overall motor score and the contralateral bradykinesia + rigidity score, but not the gait + posture score. In contrast, kinematic measures demonstrated that levodopa and pallidotomy had different effects on walking and reaching speed. Both treatments improved walking speed, and the effect was additive. Levodopa improved reaching speed before pallidotomy but did not improve it as much after pallidotomy. Additionally, pallidotomy had inconsistent effects on reaching; some subjects were faster and others were slower. The subjects who initially reached more slowly improved after pallidotomy; the subjects who initially reached more normally (faster) worsened after pallidotomy. On the basis of our results, we speculate that basal ganglia output pathways that control walking and reaching may be distinct, such that bilateral projections to the pedunculopontine area influence walking, whereas ipsilateral thalamocortical projections influence reaching.

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PubMed2006

Pallidotomy versus pallidal stimulation.

Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on-off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22-60) after the pallidotomy and 22 months (range 12-33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20-26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.

Aged↗
PubMed1998

Pallidotomy and bradykinesia: implications for basal ganglia function.

BACKGROUND AND OBJECTIVE: The scientific rationale for pallidotomy as a treatment for PD is that the lesion will reduce excessive tonic inhibition of the thalamus, thereby allowing movement to proceed more normally. If true, then PD patients who move slowly while on medication should increase movement speed following pallidotomy. To test this we used a simple motor task to determine if pallidotomy leads to an improvement in "on" motor performance when those movements are impaired before surgery. METHODS: Nine patients with PD performed elbow flexion movements "as fast as possible" while they were "on" before and 1 month after pallidotomy. Patients with mild PD and healthy control subjects were also tested. RESULTS: The clinical effects of pallidotomy were typical of those found in other studies. "Off" Unified Parkinson's Disease Rating Scale scores improved and dyskinesias were reduced. Although before surgery the patients were far slower while they were "on" than the groups of mild PD patients and healthy control subjects, there was no change in mean peak velocity while they were "on" after pallidotomy. There was no change in other mean "on" motor performance measures such as peak acceleration, peak deceleration, initiation time, and symmetry. There was a decrease in the variability of peak acceleration, symmetry, and initiation time. CONCLUSION: Despite the clinical efficacy of pallidotomy while patients were "off," bradykinesia of elbow flexion movements while patients were "on" is not affected by pallidotomy. Therefore, we conclude that the bradykinesia observed in this experiment is due to a mechanism other than excessive tonic inhibition of the motor thalamus. Our results are consistent with the idea that pallidotomy reduces the noise from the abnormally functioning basal ganglia.

Adult↗
PubMed1997

Efficacy of bilateral pallidotomy.

Unilateral pallidotomy is a safe and effective treatment for medically refractory bradykinetic Parkinson's disease, especially in those patients with levodopa-induced dyskinesia and severe on-off fluctuations. The efficacy of bilateral pallidotomy is less certain. The authors completed 11 of 12 attempted bilateral pallidotomies among 150 patients undergoing pallidotomy at New York University. In all but one patient, the pallidotomies were separated by at least 9 months. Patients were selected for bilateral pallidotomy if they exhibited bilateral rigidity, bradykinesia, or levodopa-induced dyskinesia prior to treatment or if they exhibited disease progression contralateral to their previously treated side. The Unified Parkinson's Disease Rating Scale (UPDRS) and timed upper-extremity tasks of the Core Assessment Protocol for Intracerebral Transplantation (CAPIT) were administered to all 12 patients in the "off" state (12 hours without receiving medications) preoperatively and again at 6 and 12 months after each procedure. The median UPDRS and contralateral CAPIT scores improved 60% following the initial procedure (p = 0.008, Wilcoxon rank sums test). The second pallidotomy generated only an additional 10% improvement in the UPDRS and CAPIT scores ipsilateral to the original procedure (p = 0.05). Worsened speech was observed in two cases. In the 12th case, total speech arrest was noted during test stimulation. Speech returned within minutes after stimulation was halted. Lesioning was not performed. These results indicate that bilateral pallidotomy has a narrow therapeutic window. Motor improvement ipsilateral to the first lesion leaves little room for further improvement from the second lesion and the risk of speech deficit is greatly enhanced. Chronic pallidal stimulation contralateral to a previously successful pallidotomy may prove to be a safer alternative for the subset of patients who require bilateral procedures.

Journal Article↗
PubMed2002

Subthalamic nucleus stimulation in patients with a prior pallidotomy.

OBJECT: A substantial number of patients with Parkinson disease (PD) who have undergone unilateral stereotactic pallidotomy ultimately develop symptom progression, becoming potential candidates for further surgical treatment. Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be effective in the treatment of a subset of patients with refractory PD. Microelectrode recording is performed to help localize the STN and guide final placement of the electrode. Potential alterations in physiological features of the STN after pallidotomy may complicate localization of this structure in this group of patients. METHODS: Bilateral STN DBS surgery guided by microelectrode recording was performed in six patients who had undergone previous unilateral pallidotomies. Physiologically obtained parameters of the STN, including trajectory length, mean firing rate, cell number, and cell density were calculated. These data were compared with those from the side without prior pallidotomy within each patient, as well as with those from our series of 49 subthalamic nuclei explored in 26 patients who had not undergone prior pallidotomy but who underwent bilateral STN stimulator placement. In all patients, analysis of STN cellular activity on the side ipsilateral to the pallidotomy demonstrated a lower mean firing frequency than on the contralateral, intact side. The physiological features on the intact side were not significantly different from those found in our series of patients who had not undergone prior pallidotomy. CONCLUSIONS: Physicians who perform STN surgery in patients with prior pallidotomy should be aware of the electrophysiological differences between the STN that had undergone pallidotomy and the one that had not, to avoid prolonging recording time to search for the typical STN. The implications of these findings for the current models of information processing in the basal ganglia are discussed.

Adult↗
PubMed2006

Subthalamic deep brain stimulation in patients with a previous pallidotomy.

The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinson's Disease Center who underwent STN DBS after prior unilateral pallidotomy. Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age- and sex-matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 +/- 10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 +/- 14.3 to 34.9 +/- 12.8, and the UPDRS dyskinesia score improved from 1.8 +/- 1.0 to 0.8 +/- 0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 +/- 10.2 years) improved by 16.0% from 53.1 +/- 9.7 (range, 42-68) to 44.6 +/- 11.1 (range, 25-67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 +/- 11.1 to 25.7 +/- 18.9, (16.0% vs. 49.9%; P < 0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy. This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection.

Adult↗