Cognitive and behavioral changes after unilateral posteroventral pallidotomy: relationship with lesional data from MRI.

We investigated cognitive and behavioral changes after unilateral posteroventral pallidotomy, and their relationship with lesion size and location as identified in magnetic resonance image quantitative analysis. Fifteen consecutive patients with Parkinson's disease were assessed neuropsychologically before and after unilateral posteroventral pallidotomy (five right and 10 left). Immediate postsurgery evaluation (1 week) demonstrated significant worsening of memory, motor learning, motor speed, and verbal fluency. In the 3-month follow up, learning, memory, and speed returned to the presurgical level, but verbal fluency remained below the baseline. Significant improvements were observed in visuospatial functions and obsessive-compulsive behavior. Lesional volume did not correlate with neuropsychologic changes. Left lesions produced more impairment in verbal fluency than right-sided lesions. Regression analysis identified two lesional areas in the pallidum mediale internum. These regions accounted for 68% of the variance in the visuospatial changes.     

Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson's disease.

Bilateral subthalamic deep brain stimulation (STN-DBS) and continuous subcutaneous infusion of apomorphine (APM-csi) can provide a comparable improvement on motor function in patients with advanced Parkinson's disease (PD), but the mechanisms by which both therapies exert their effects are different. We analyzed the cognitive effects of APM-csi. We also compared neuropsychological effects induced by STN-DBS and APM-csi in advanced PD to ascertain the neuropsychological aspects relevant in determining the therapeutic procedure that is the most appropriate in a particular patient. We studied 9 patients treated with STN-DBS and 7 patients with APM-csi. Neuropsychological measures included Rey's Auditory-Verbal Learning, Stroop, Trail Making, phonetic verbal fluency, and Judgment of Line Orientation tests. In the APM-csi group, significant changes were not observed in the neuropsychological tests performance. By contrast, in the STN-DBS group, moderate worsening was found in phonetic verbal fluency and Stroop Naming scores that was partially reversible at long-term follow-up and did not have consequences on regular activities. Consequently, these findings could be interpreted as being not relevant in deciding the most suitable treatment in a given patient.     

Depressed mood and memory impairment before and after unilateral posteroventral pallidotomy in Parkinson's disease

This study evaluated poor mood state as a moderator of changes in verbal recall ability from before to after unilateral posteroventral pallidotomy in 54 individuals with advanced Parkinson's disease. Repeated-measures analysis of covariance (controlling for motor disease severity) indicated that left-posteroventral pallidotomy subjects with depressed mood performed more poorly on measures of verbal list learning and story recall compared to nondepressed subjects or right-posteroventral pallidotomy subjects with depressed mood both before and after surgery. The results suggest that depressed mood should be taken into account when interpreting memory test performance in Parkinson's disease surgical candidates both before and after surgery.     

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.     

Visuospatial deficits in Parkinson's disease assessed by judgment of line orientation test: error analyses and practice effects.

The Benton's Judgment of Line Orientation (JLO) is one of the tests most frequently used to assess visuospatial function. The aim of the present study was to analyze qualitative errors in Parkinson's disease (PD) following the method described by Ska, Poissant, and Joanette (1990) and to determine possible practice effects of this test. The JLO was administered to 76 idiopathic PD patients and 76 matched normal controls. The analyses of errors showed several qualitative differences between groups. Parkinson's patients made a greater proportion of complex intraquadrant errors and horizontal line errors, while they showed fewer simple intraquadrant errors than controls. The JLO test was also administered twice in an interval of 20 min in a subsample of 25 PD patients and 25 normal controls. The results did not show significant differences between the two administrations, indicating that the test is free of practice effects. In conclusion, these data provide further evidence for the existence of visuospatial deficits in PD. Moreover, the JLO has proved to be an appropriate test for the assessment of the visuospatial function in patients who require a neuropsychological follow up.     

Effects of unilateral posteroventral pallidotomy on 'on-off' cognitive fluctuations in Parkinson's disease

In Parkinson's disease, cognitive performance can vary according to levodopa levels (on-off states). Both positive and negative effects of dopaminergic stimulation have been reported. Pallidotomy is also able to change cognitive performance, in addition to levodopa pharmacokinetics. The aim of this investigation was to study the effects of pallidotomy on cognitive on-off fluctuations in Parkinson's disease. A brief neuropsychological battery was administered to 15 PD patients during on and off states before and after surgery. Before pallidotomy, patients performed better in the on condition on Trail Making test B; after pallidotomy levodopa no longer improved performance, and the interaction between surgery and state was significant. In relation to the difference between preoperative and postoperative performance in Trail Making B test, there was a significant postsurgical improvement only in off state. Verbal fluency decreased after pallidotomy in both on and off conditions. Our results suggest that pallidotomy can change the effects of levodopa on neuropsychological functions.     

Neuropsychological outcome after unilateral pallidotomy for the treatment of Parkinson's disease

OBJECTIVE: To assess the long term cognitive outcome of unilateral posteroventral pallidotomy (PVP) and the overall efficacy of the surgery. METHODS: Forty two (29 left and 13 right PVP) patients with Parkinson's disease underwent neurological and neuropsychological testing before PVP and at 3 and 12 months after PVP. The neuropsychological testing battery emphasised measures of verbal learning and memory, visuospatial abilities, speed of information processing, executive functioning, and affective functioning. RESULTS: All patients demonstrated motor improvements after surgery during their off state, and 86% of patients also showed improvements in motor functioning in their on state. Repeated measures ANOVA showed significant improvements in confrontational naming, visuospatial organisation, and affective functioning 3 months and 12 months after surgery, with inconsistent improvements in executive functioning 12 months post-PVP. Patients demonstrated a transient impairment in verbal memory, with verbal learning performance returning to baseline 12 months post-PVP after a significant decline 3 months after PVP. When three patients with lesions extending outside of the PVP were excluded from the analysis, a decline in verbal fluency performance after PVP was not found to be significant. Differences due to side of lesion placement were not found on any of the cognitive measures. CONCLUSIONS: In the largest long term follow up study reported to date, the cognitive changes found up to a year after PVP are minimal compared with the robust improvements in motor function. The findings highlight the need to investigate the relation between the specific fibre tracts affected by the lesions and cognitive outcome.     

Neuropsychological and psychiatric sequelae of pallidotomy for PD: clinical trial findings

OBJECTIVE: To evaluate the neuropsychological and psychiatric sequelae of unilateral posterior pallidotomy for treatment of PD. METHODS: Patients with idiopathic PD completed baseline and 3- and 6-month assessments after random assignment to an immediate surgery (n = 17) or medical management (n = 16) group. RESULTS: Compared with the medical management group, the immediate surgery group with single lesions centered on the posterior internal pallidum showed superior naming and response inhibition, better verbal recall at 6 months, but greater distractibility, a tendency toward lower phonemic fluency, and a transient (3 months' only) semantic fluency deficit. The group with left lesions had more neuropsychological deficits than the group with right lesions or the medical management group, although these occurred mainly at 3 (but not 6) months. At 6 months, the patients with left lesions showed better verbal memory retention than the patients with right lesions. On most measures, the pattern of individual clinical change did not differ as a function of surgery or lesion laterality, with the exception of a higher frequency of decline in phonemic fluency in the patients with left lesions at 6 months. Although psychiatric status did not change overall, a history of depression tended to increase the risk of a depressive episode following surgery. CONCLUSIONS: Well-targeted, uncomplicated, unilateral pallidotomy does not produce overall neuropsychological or psychiatric change, although there are subtle changes on specific measures sensitive to frontal lobe function.     

Effects of pallidotomy and bilateral subthalamic stimulation on cognitive function in Parkinson disease

Unilateral pallidotomy and bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinsons disease (PD) have demonstrated a positive effect on motor functions. However, further studies are needed of the unintended cognitive effects accompanying these new surgical procedures. We studied the consequences of unilateral pallidotomy and STN-DBS on cognitive function in a controlled comparative design. Sixteen consecutive PD patients were assessed before and 6 months after unilateral pallidotomy (n = 8) and bilateral STN-DBS (n = 8). The same assessments were performed in a control group of eight non-operated matched PD patients recruited from surgery candidates who refused operation. The neuropsychological battery consisted of test measuring memory, attention, arithmetic, problem solving and language, as well as visuospatial, executive and premotor functions. An analysis of variance (factors time and treatment) was applied. No statistically significant differences were found in the presurgical evaluation of clinical and demographic data for the three treatment groups. The controlled comparison between presurgical and postsurgical performance revealed no significant changes in the cognitive domains tested in the pallidotomy group. The STN-DBS group showed a selective significant worsening of semantic verbal fluency (p = 0.005). This controlled comparative study suggests that neither unilateral pallidotomy nor bilateral STN-DBS have global adverse cognitive consequences, but bilateral STN-DBS may cause a selective decrease in verbal fluency.     

Evaluation of the stability of neuropsychological functioning after acute episodes of schizophrenia: one-year followup study.

Few studies have evaluated the longitudinal stability of neuropsychological deficits in schizophrenia. In the present study, 39 inpatients with DSM-III-R schizophrenia were administered a comprehensive battery of neuropsychological tests after achieving sufficient clinical recovery to warrant discharge, and again 1 year after the first assessment during a nonacute period. Significant improvement in neuropsychological functioning from the first to the second assessment was observed on several tasks, including the following: Trails A and B, Digit Symbol, Judgment of Line Orientation, recognition memory on the Rey Auditory Verbal Learning Test, the Wisconsin Card Sort, and Finger Tapping. These improvements were unrelated to treatment history, and were similar in first episode and chronic cases. For many patients, the improvement in functioning brought test performance into line with normative scores from test standardization samples. These results indicate that considerable improvement in neuropsychological functioning can occur in schizophrenic patients over the months following an acute episode of illness, and that recovery of cognitive functioning can occur after substantial clinical recovery from an acute episode of illness has already been achieved.     

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.     

Neuropsychological sequelae of bilateral posteroventral pallidotomy

OBJECTIVES: To document the impact of bilateral posteroventral pallidotomy on cognitive status. METHODS: 17 patients with Parkinson's disease were evaluated with a neuropsychological battery before and six months after bilateral pallidotomy. A comparison group (n = 8) was also assessed at six month intervals. Outcome variables were tests of memory, language, visuospatial function, attention, executive skills, and depression. RESULTS: Despite a large number of variables studied, a significant postsurgical change was found only in performance of the tower of London task, a measure of planning abilities. The effect size of this change was larger than that of the comparison group, and a reliable change index score established that 5 of 13 surgical patients had statistically reliable reductions in planning performance. CONCLUSIONS: Patients with a young age of onset and long duration of Parkinson's disease who underwent bilateral pallidotomy had a relatively circumscribed reduction in neuropsychological functioning, being limited to motor planning efficiency. These data suggest that the cognitive role of the posteroventral globus pallidus is limited, at least in people with Parkinson's disease.     

Unilateral pallidotomy for Parkinson's disease: speech, motor, and neuropsychological outcome measurements

We studied the effects of unilateral medial pallidotomy in the first 57 consecutive Parkinson's disease (PD) patients undergoing this MRI/electrophysiologically guided procedure at our institution, obtaining qualitative and quantitative measures of speech, motor function, activities of daily living, and neuropsychological functioning at 3 and 12months post-operatively. Speech intelligibility was typically preserved, declining mildly in one-third of patients post-operatively. Pallidotomy significantly improved motor function similarly in patients >/=65 or <65years (n=20). Cognitive abilities generally remained stable following surgery; however, performance on measures of letter fluency and semantic fluency declined in patients with left pallidotomies. We conclude that in our series mild deterioration in speech may occur with unilateral pallidotomy in patients otherwise responsive to this treatment.     

Qualitative analysis of verbal fluency before and after unilateral pallidotomy

This study examined qualitative aspects of phonemic and semantic fluency before and after unilateral pallidotomy in patients with intractable Parkinson's Disease (PD). Specifically, clustering (number of similar words generated sequentially) and switching (number of changes or switches from one cluster to another) were evaluated for both fluency tasks. Twenty-five PD patients participated and were grouped according to whether they improved or declined on each of the fluency measures after surgery. Decliners evidenced decreased switching, but not clustering, suggesting difficulties with set-shifting and cognitive flexibility rather than a diminished semantic store of information or retrieval difficulties. Though consistent with hypotheses about difficulties with executive processing after pallidotomy, a series of correlational analyses with composite measures of neuropsychological functioning (attention, language, executive processing, and memory) suggest caution in interpreting these findings. In these analyses, clustering was not meaningfully related to any of the composites whereas switching was significantly and positively related to the composites; this pattern emerged, for the most part, on both fluency measures before and after surgery. Switching, but not clustering, was also significantly and positively correlated with total words generated on both semantic and phonemic fluency. Switching changes across time were also related to DRS changes post-pallidotomy. These correlational analyses challenge the specificity of the switching variable and, more broadly, the validity of these qualitative measures of verbal fluency.     

Motor and cognitive sequelae of unilateral pallidotomy in intractable Parkinson's Disease: electronic measurement of motor steadiness is a useful outcome measure

This study examined the short-term motor and cognitive sequelae of unilateral posterolateral pallidotomy for patients with intractable Parkinson's Disease (PD). Unique to this study was the inclusion of electronic motor steadiness instrumentation among pre- and postsurgical assessment procedures. Fifteen PD patients underwent right-sided surgery and 10 underwent left-sided surgery; patients were evaluated 1 month presurgery and approximately 3 months postsurgery. Motorically, there were no significant changes in grooved pegboard or maze-drawing performances, but patients evidenced significantly improved steadiness, particularly in the hand contralateral to the side of surgery. Cognitively, there were no significant decrements on postsurgery composite variables comprised of well-known tests of attention, executive functioning, delayed memory or recognition memory; these findings were similar for patients with either left- or right-sided surgery. There was, however, a significant change in language abilities among a subset of patients. This change was evident in the decline in verbal fluency in PD patients who underwent left-sided pallidotomy, a finding that has consistently emerged in pallidotomy outcome studies. This decline is discussed in terms of evidence that suggests that the basal ganglia consist of several separate, but parallel circuits, some of which are important for cognition.     

Neurocognitive functioning in patients with first-episode schizophrenia 1 year from onset in comparison with patients 5 years from onset

Objective. The course of neurocognitive deficits in schizophrenia has not yet been established. Therefore, we followed patients with first-episode schizophrenia to verify the course of these deficits. Methods. In Study 1, tests of neurocognitive functioning were administered to patients with first-episode schizophrenia (FE group) every 6 months. Of the 26 patients who completed the baseline assessment, 19 completed a 6-month follow-up, and 13 completed a 1-year follow-up. In Study 2, 19 patients in FE group at 6-months when the neuropsychological measures was less influenced by psychotic symptoms and other patients who experienced schizophrenia 5-years earlier (5-year group) were compared. Results. In Study 1, verbal memory, motor speed, and executive functions significantly improved at the 1-year follow-up. In Study 2, patients in 5-year group performed worse in verbal memory and executive functions than patients in FE at 6-month group, but marginally but significantly better in verbal fluency. Conclusions. Verbal memory, executive functions, and verbal fluency were significantly different between 5-year group and FE at 6-month group, and may indicate progression of schizophrenia. Executive functions may reflect the state of psychosis. Working memory and processing speed which did not change significantly from onset are needed to verify the course in further research.     

Impacto de la estimulación subtalámica a largo plazo sobre la situación cognitiva de los pacientes con enfermedad de Parkinson avanzada

ObjectiveThe aim of this study was to evaluate the effects of deep brain stimulation of the subthalamic nucleus (DBS-SN) on cognitive function in patients with Parkinson's disease (PD) 5 years after surgery.Material and methodsWe conducted a prospective study including 50 patients with PD who underwent DBS-SN (62.5% were men; mean age of 62.2 ± 8.2 years; mean progression time of 14.1 ± 6.3 years). All patients were assessed before the procedure and at one year after surgery; 40 patients were further followed up until the 5-year mark. Follow-up assessments included the following neuropsychological tests: Mini–Mental State Examination (MMSE), Mattis Dementia Rating Scale (MDRS), letter-number sequencing of the WAIS-III (WAIS-III-LN), clock-drawing test, Rey auditory verbal learning test (RAVLT), Benton Visual Retention Test (BVRT), Judgment of Line Orientation (JLO) test, FAS Phonemic Verbal Fluency Test, Stroop test, and the Montgomery-Asberg Depression Rating Scale (MADRS).ResultsPatients were found to score lower on the MMSE (−0.89%), clock-drawing test (−2.61%), MDRS (−1.72%), and especially phonemic (−13.28%) and sematic verbal fluency tests (−12.40%) at one year after surgery. Delayed recall on the RAVLT worsened one year after the procedure (−10.12%). At 5 years, impairment affected mainly verbal fluency; scores decreased an additional 16.10% and 16.60% in semantic and phonemic verbal fluency, respectively. Moderate decreases were observed in immediate recall (−16.87%), WAIS-III-LN (−16.67%), and JLO test (−11.56%).DiscussionIn our sample, DBS-SN did not result in global cognitive impairment 5 years after surgery. Verbal function was found to be significantly impaired one year after the procedure. Impaired learning and visuospatial function may be attributed to degeneration associated with PD.     

Neuropsychological performance following staged bilateral pallidal or subthalamic nucleus deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) has the potential to significantly reduce motor symptoms in advanced Parkinson's disease (PD). Controversy remains about non-motor effects of DBS and the relative advantages of treatment at two brain targets, the globus pallidus internus (GPi) and the subthalamic nucleus (STN). We investigated effects of DBS on neuropsychological functioning in 42 patients with advanced PD randomly assigned to receive staged bilateral DBS surgery of either the GPi or STN. Patients underwent neuropsychological assessment prior to and 6 months after unilateral surgery. Twenty-nine subsequently underwent surgery to the contralateral side and completed a second follow-up neuropsychological evaluation 15 months later. Unilateral treatment resulted in small but statistically significant reductions in performance on several measures, including verbal fluency and working memory. A similar pattern was observed after bilateral treatment. Reductions in verbal associative fluency were significant only after left-sided treatment. There were few significant differences related to treatment at the two surgical targets. Supplementary analyses suggested that decrements in select neuropsychological domains following DBS are unrelated to age or post-surgical reduction in dopaminergic medication dose. Findings are discussed with reference to possible causes of neuropsychological decline and the need for further controlled studies of specific neuropsychological effects of DBS.     

The neuropsychology of de novo patients with idiopathic Parkinson's disease: the effects of age of onset

One hundred de novo patients with Parkinson's disease (PD) were classified into two groups according to age of onset of symptoms. Seventy two patients were under 70 years and 28 were 70 years and over. All patients were given neurological and neuropsychological assessments, and the severity of the signs was rated on a modified Columbia scale. The neuropsychological assessment was also administered to 50 age-and-education-matched controls. The neuropsychological test battery included tests of verbal learning, visual memory, verbal fluency, visuospatial skill, simple and choice reaction time, language and maze learning. The late-onset patients had significant impairment in nonverbal reasoning, auditory verbal learning, visual memory and choice reaction time in contrast to early-onset patients and controls. A relationship was found between bradykinesia and widespread cognitive impairment. Severity of tremor was found to be significantly correlated with impairment in auditory verbal learning, visual memory and increased choice reaction time, while rigidity was found to be associated with cognitive impairment in verbal fluency and visuospatial skill. Using DSM II criteria, 39% of the late-onset and 8% of the early-onset group were classified as demented. Dementia was more common in patients with bilateral symmetrical disease and in those patients with marked tremor and bradykinesia. The pattern of cognitive impairment in PD was consistent with that associated with a subcortical dementia. This study confirms that the expression of PD is markedly influenced by the age of onset.     

Long term outcome of unilateral pallidotomy: follow up of 15 patients for 3 years

OBJECTIVES: With the advent of new antiparkinsonian drug therapy and promising results from subthalamic and pallidal stimulation, this study evaluated the long term efficacy of unilateral pallidotomy, a technique which has gained popularity over the past decade for the management of advanced Parkinson's disease. METHODS: The 15 patients reported here are part of the original cohort of 24 patients who underwent posteroventral pallidotomy for motor fluctuations and disabling dyskinesias 3 years ago as part of a prospective study. Evaluation scales included the unified Parkinson's disease rating scale, the Goetz dyskinesia scale, and the Purdue pegboard test. RESULTS: When compared with the prepallidotomy scores, the reduction in the limb dyskinesias and off state tremor scores persisted on the side contralateral to pallidotomy at the end of 3 years (dyskinesias were reduced by 64% (p<0.01) and tremor by 63% (p<0.05). Other measures tended to deteriorate. The dosage of antiparkinsonian medications did not change significantly from 3 months prepallidotomy to 3 years postpallidotomy. CONCLUSIONS: Although unilateral pallidotomy is useful in controlling the contralateral dyskinesias and tremor 3 years after surgery, all other early benefits disappear and activities of daily living continue to worsen.