Unilateral and bilateral pallidotomy for idiopathic Parkinson's disease: a case series of 115 patients.

Lesioning of the internal pallidum is known to improve the symptoms of idiopathic Parkinson's disease (PD) and alleviate dyskinesia and motor fluctuations related to levodopa therapy. The benefit obtained contralateral to a single lesion is insufficient in some cases when symptoms are bilaterally disabling. However, reports of unacceptably high rates of adverse effects after bilateral pallidotomy have limited its use in such cases. We report on the outcome of unilateral (UPVP) and bilateral (BPVP) posteroventral pallidotomy in a consecutive case series of 115 patients with PD in the United Kingdom and Australia. After 3 months, UPVP resulted in a 27% reduction in the off medication Part III (motor) Unified Parkinson's Disease Rating Scale score and abolition of dyskinesia in 40% of cases. For BPVP, these figures were increased to 31% and 63%, respectively. Follow-up of a smaller group to 12 months found the motor scores to be worsening but benefit to dyskinesia and activities of daily living was maintained. Speech was adversely affected after BPVP, although the change was small in most cases. Unilateral and bilateral pallidotomy can be performed safely without microelectrode localisation. Bilateral pallidotomy appears to be more effective, particularly in reducing dyskinesia; in our experience, the side effects have not been as high as reported by other groups.     

Weight gain following unilateral pallidotomy in Parkinson's disease

OBJECTIVE: To determine the clinical correlates and infer pathogenesis of weight gain following pallidotomy in patients with Parkinson's disease (PD). BACKGROUND: Surgical ablation of the globus pallidus internus (GPi) improves levodopa induced dyskinesias, moderately improves most other "cardinal" manifestations of PD, and has been noted to result in increased weight. METHODS: We incorporated Unified Parkinson's Disease Rating Scales (UPDRS) subscales, the Beck depression inventory and feeding questionnaire data into a linear regression model in order to determine which post-surgical change(s) may lead to weight gain over the first year following pallidotomy, n = 60. RESULTS: The mean weight gain 1 year after pallidotomy was 4.0 +/- 4.1 kg. Improvement in "off" motor scores (P < 0.005), especially gait subscores (P<0.0001), and to a lesser extent improvement in "on" motor scores (P<0.05) predicted weight gain. Changes in dyskinesia ratings, mood, food intake, dysphagia, levodopa dose, weight loss in the year prior to pallidotomy, age, and duration of PD did not correlate with subsequent weight gain. CONCLUSION: The high correlation between post-pallidotomy weight gain and "off" motor scores, suggests that this phenomenon is related to some change in underlying homeostasis associated with changes in the cardinal manifestations of PD itself, rather than secondary changes resultant from the surgery.     

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.     

Cognitive effects of unilateral posteroventral pallidotomy: a 4-year follow-up study.

We assessed the long-term neuropsychological effects of unilateral posteroventral pallidotomy in Parkinson's disease. Eleven Parkinson's disease patients, from an original cohort of 15 consecutive patients who underwent pallidotomy, were evaluated. A neuropsychological battery was administered to each patient before (3 days) and after (3 months and 4 years) surgery during the effects of levodopa. The following tests were administered: Rey's Auditory-Verbal Learning Test, Visual Associative Learning test from the Wechsler Memory Scale-Revised, Luria's motor alternation, Benton's Judgment of Line Orientation, Trail Making, phonetic verbal fluency, Stroop test, Petrides' working memory tasks, Beck's depression questionnaire and the Maudsley obsessional-compulsive inventory. In the 3-month postoperative assessment, there was a significant worsening in phonetic verbal fluency and an improvement in Benton's Judgment of Line Orientation test. In the 4-year follow-up assessment, phonetic verbal fluency and Benton's Judgment of Line Orientation test returned to baseline scores. Although there was no significant difference between pre- and postsurgical scores for long-term visual associative memory, there was a significant deterioration between 3-month and 4-year follow-up performances. Our results suggest that unilateral posteroventral pallidotomy may produce transient changes in prefrontal and visuospatial functions, but there is no evidence of permanent neuropsychological effects.     

Effects of unilateral pallidotomy on voluntary movement, and simple and choice reaction times in Parkinson's disease.

We studied the effects of unilateral pallidotomy on motor execution and reaction times in patients with moderately advanced Parkinson's disease (PD). Twelve consecutive patients (7 men, 5 women; all right-handed) underwent left-side microelectrode-guided pallidotomy. In addition to clinical rating, reaction time (RT) tests and repetitive movements of the contralesional hand/arm were carried out at baseline and 2 to 3 months after surgery while patients were on optimal medical regimens (on period). The initiation time in both simple reaction time (SRT) and choice reaction time (CRT) improved significantly after pallidotomy (P < 0.05), whereas no effect was observed on the choice processing time, which was calculated by subtracting the mean value of the onset of SRT from that of CRT. Pallidotomy resulted in significant improvement of repetitive movements such as hand pronation/supination and finger-tapping (P < 0.002, P < 0.005, respectively). Improvements in RT tests and repetitive movements suggest that pallidotomy may enhance attention and motor function. These effects are probably mediated through the pallido-thalamic-cortical neural circuitry.     

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.     

Static balance impairment and its change after pallidotomy in Parkinson's disease.

We compared postural sway parameters during a 1-minute quiet stance in 28 patients with idiopathic Parkinson's disease (PD) in off phase with those in 17 age-matched normal subjects and investigated differences in the sway parameters before and after unilateral pallidotomy in 16 PD patients. The PD patients showed larger sway area (SA) and longer total sway path length (SPL) compared with normal subjects. Total SPL after subtraction of tremor effect did not differ from that in normal subjects. The shift of the mean center of foot pressure (CFP) position from the first 30 seconds to the last 30 seconds showed that the CFP tended to move forward in PD patients compared with normal subjects and to move laterally more in PD patients than normal subjects, especially in those with less severity (Unified Parkinson's Disease Rating Scale, motor score < 40). After the operation, there was little change in either SA or lateral movement of CFP, but forward movement of CFP and total SPL tended to be normalized, along with an improvement of major parkinsonian symptoms. From these results, it is concluded that SPL elongation significantly involves tremor effect, forward movement of CFP in PD derives from basal ganglia dysfunction, and SA enlargement and large lateral movement of CFP may be caused partly by compensatory movements or by dysfunction outside the basal ganglia circuitry.     

The role of high‐intensity focused ultrasound as a symptomatic treatment for Parkinson's disease

MR‐guided focused ultrasound is a novel, minimally invasive surgical procedure for symptomatic treatment of PD. With this technology, the ventral intermediate nucleus, STN, and internal globus pallidus have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures. In a double‐blinded, prospective, sham‐controlled randomized controlled trial of MR‐guided focused ultrasound thalamotomy for treatment of tremor‐dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open‐label trial of MR‐guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open‐label trials of MR‐guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR‐guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high‐quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR‐guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR‐guided focused ultrasound lesions, ideal timing of MR‐guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions. © 2019 International Parkinson and Movement Disorder Society     

From functional neurosurgery to "interventional" neurology: survey of publications on thalamotomy, pallidotomy, and deep brain stimulation for Parkinson's disease from 1966 to 2001.

Articles on surgery for Parkinson's disease (PD), published between 1966 and 2001, were reviewed with respect to whether the first author had a neurosurgical affiliation, and whether the papers appeared in neurosurgical or non-neurosurgical journals. Between 1966 and 1979, neurosurgeons and non-neurosurgeons published almost equally on surgery for PD in both neurosurgical and non-neurosurgical journals; between 1980 and 1995, the majority of publications were by neurosurgeons in neurosurgical journals; and after 1995, non-neurosurgeons were more often first authors of surgical publications and these were more frequent in non-neurosurgical journals. The fact that the first author of surgical publications on PD is often a non-neurosurgeon may have some bearing on the reported results of surgery.     

Subthalamic nucleus deep brain stimulation for parkinson's disease after successful pallidotomy: clinical and electrophysiological observations.

Unilateral pallidotomy is an effective treatment for contralateral parkinsonism and dyskinesia, yet symptoms progress in many patients. Little is known about whether such patients obtain a useful response to subsequent bilateral subthalamic nucleus deep brain stimulation (STN DBS). Changes in Unified Parkinson's Disease Rating Scale (UPDRS) Motor and Activities of Daily Living (ADL) scores, medication requirements, and dyskinesias were measured. Clinical outcomes were compared to patients with de novo STN DBS. Neuronal recordings were performed. STN DBS resulted in a significant reduction in UPDRS Motor scores (42.1%; 95% confidence interval [CI], 26.9-57.4; P = 0.03), comparable with de novo STN DBS surgery (41%; 95% CI, 26-46%; P < 0.001). There was also less change in dyskinesia duration and disability scores (P = 0.017, 0.005). There were no side-to-side differences clinically or in the STN neuronal firing rates and patterns. Bilateral STN DBS is safe and efficacious in improving motor symptoms in patients with prior pallidotomy.     

Long‐term effect of unilateral pallidotomy on levodopa‐induced dyskinesia

Unilateral pallidotomy has been effectively used to treat parkinsonism and reduce levodopa induced dyskinesia (LID). We sought to determine the long‐term effects of pallidotomy on LID in 10 patients who had initial benefit from pallidotomy but went on to require DBS surgery for symptom progression. The Dyskinesia Rating Scale (DRS) was used to rate and quantify LID in a blinded fashion. Though sample size was small, there was a trend towards a reduction in LID lasting up to 12 years suggesting that posteroventral pallidotomy may provide sustained benefit in reducing LID. © 2010 Movement Disorder Society     

Action fluency in Parkinson's disease: a follow-up study.

The impairment in action fluency task present in Parkinson's disease (PD) patients has been previously interpreted as an indicator of conversion from PD to PD with dementia or as a grammatical deficit for verbs and ascribed to a frontostriatal loop pathophysiology. In the present study, 20 patients with PD without dementia were longitudinally tested with overall cognitive decline scales and semantic, letter, and action fluency tasks in a 24-month follow-up study. In comparison with healthy age-matched controls, PD patients showed a stable and consistent impairment on action fluency without any sign of cognitive decline. Our findings suggest that action fluency task may be an early sign of impairment of frontostriatal circuits in PD and it cannot be considered an indicator of conversion from PD to PD with dementia.     

Cognitive profile of Parkinson's disease patients: a comparative study between early-onset and late-onset Parkinson's disease

Aim: To investigate the influence of onset age on the occurrence and progression of cognitive dysfunction using neuropsychological tests and the electrophysiological component P300 in both early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) patients. Methods: A cohort of 76 EOPD patients and 166 LOPD patients was recruited for this study. Demographic information and clinical features, including age, disease duration, education level, family history, the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr stage, and depression scores were documented for each patient. The Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale – Revised, Chinese version (WAIS-RC) and Wechsler Memory Scale – Revised, Chinese version (WMS-RC) were used. In addition, P300 was also examined to assess cognitive function. Results: Although EOPD patients had longer disease duration, their cognitive dysfunction progressed more slowly. The MoCA tests revealed that EOPD patients had higher scores in visuospatial function, attention, delayed recall, and orientation than the LOPD patients. The difference between the two groups on the WMS-RC test did not reach significance, whereas the scores in executive function, visuospatial function and attention as measured on the WAIS-RC test were significantly lower in the LOPD group. In addition, P300 latencies were markedly delayed and P300 amplitudes were reduced in the LOPD group. Conclusions: The current findings demonstrated that cognitive dysfunction progressed more slowly in the EOPD group. Although the LOPD patients exhibited shorter disease durations, their cognitive abilities, including executive function, visuospatial function and attention, may have been impaired.     

The effects of transdermal rotigotine on non-motor symptoms of Parkinson's disease: a multicentre,observational, retrospective,post-marketing study

Aim: This study evaluated the effect of ≥6 months of transdermal rotigotine on non-motor and motor symptoms of patients with advanced Parkinson's disease. Materials and methods: The study was conducted in Spain between September 2011 and December 2012 (ClinicalTrials.gov: NCT01504529). The primary efficacy variable was the change from baseline in non-motor symptoms, as assessed by changes in Parkinson's Disease Non-Motor Symptoms Questionnaire total scores at 6 months. Secondary endpoints included the assessment of motor symptoms by Unified Parkinson's Disease Rating Scale III scores. Results: Data from 378 patients (mean age: 70.2 years; 56.9% male) with Parkinson's disease receiving rotigotine from were collected. Mean disease duration was 6.1 years, and mean rotigotine treatment duration was 45.6 months. Rotigotine reduced non-motor symptoms by 14.6% (mean change from baseline in Parkinson's Disease Non-Motor Symptoms Questionnaire: ?1.5 ± 3.4; p < 0.0001). The majority of patients (58.2%) had improved non-motor symptoms at 6 months. Comparing the baseline versus study end, fewer patients experienced events in the urinary (78.6% vs. 73.3%; p = 0.0066), sleep (82.8% vs. 72.8%; p < 0.0001) and mood/cognition (77.3% vs. 66.4%; p < 0.0001) domains of the Parkinson's Disease Non-Motor Symptoms Questionnaire. Mean motor symptoms were reduced from baseline by 8.0% (mean change from baseline in Unified Parkinson's Disease Rating Scale III: ?2.6 ± 8.0; p < 0.0001). Conclusions: In clinical practice in Spain, rotigotine may be an effective treatment to reduce the non-motor and motor symptoms in patients with advanced Parkinson's disease.     

Qigong exercise for the symptoms of Parkinson's disease: a randomized, controlled pilot study.

Irrespective of limited evidence, not only traditional physiotherapy, but also a wide array of complementary methods are applied by patients with Parkinson's disease (PD). We evaluated the immediate and sustained effects of Qigong on motor and nonmotor symptoms of PD, using an add-on design. Fifty-six patients with different levels of disease severity (mean age/standard deviation [SD], 63.8/7.5 years; disease duration 5.8/4.2 years; 43 men [76%]) were recruited from the outpatient movement disorder clinic of the Department of Neurology, University of Bonn. We compared the progression of motor symptoms assessed by Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) in the Qigong treatment group (n = 32) and a control group receiving no additional intervention (n = 24). Qigong exercises were applied as 90-minute weekly group instructions for 2 months, followed by a 2 months pause and a second 2-month treatment period. Assessments were carried out at baseline, 3, 6, and 12 months. More patients improved in the Qigong group than in the control group at 3 and 6 months (P = 0.0080 at 3 months and P = 0.0503 at 6 months; Fisher's exact test). At 12 months, there was a sustained difference between groups only when changes in UPDRS-III were related to baseline. Depression scores decreased in both groups, whereas the incidence of several nonmotor symptoms decreased in the treatment group only.     

Prevalence of stroke in Parkinson's disease: a postmortem study.

The results of previous epidemiological studies of the relationship between Parkinson's disease and stroke have been conflicting; some showing a reduced risk of ischaemic and haemorrhagic stroke during life, and others indicating an increased likelihood of stroke-related death. We compared the frequency of cerebral infarcts and haemorrhages at postmortem in 100 cases of pathologically verified idiopathic Parkinson's disease and 100 age-matched control brains. No significant differences were found in the numbers of infarcts or haemorrhages or stroke-related deaths between the two groups. Our findings do not indicate either a protective effect against stroke, or a greater susceptibility to death from stroke, in the population studied.     

Does the ADL part of the unified Parkinson's disease rating scale measure ADL? An evaluation in patients after pallidotomy and thalamic deep brain stimulation

We evaluated the impact of pallidotomy and thalamic deep brain stimulation (DBS) on disability of patients with advanced Parkinson's disease and investigated whether the activities of daily living (ADL) section of the Unified Parkinson's Disease Rating Scale (UPDRS) measures disability in everyday life. Nineteen patients who had pallidotomy and 14 patients who had thalamic DBS were followed for a mean of 11 months. Evaluation tools included the UPDRS as well as a generic ADL scale, called ADL taxonomy. The 13 items belonging to the ADL part of the UPDRS were classified into two categories according to whether the items described a disability or impairment. The total scores of the UPDRS Part II (ADL) were ameliorated in both the pallidotomy and the thalamic DBS groups. When analysing separately the scores from the two categories of the ADL part of the UPDRS, i.e., disability and impairment, only patients who underwent pallidotomy showed improvement in disability-related items. These findings were confirmed when evaluating the patients with the ADL taxonomy. The ADL part of the UPDRS contains a mixture of impairment- and disability-related items. This mixture may confound results when evaluating the impact of surgery on ADL.