Changes in cognition and health-related quality of life with unilateral thalamotomy for Parkinsonian tremor

Changes in cognition and health-related quality of life with unilateral thalamotomy for Parkinsonian tremor

Available online at www.sciencedirect.com Journal of Clinical Neuroscience 16 (2009) 44–50 www.elsevier.com/locate/jocn Clinical Study Changes in c...

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Available online at www.sciencedirect.com

Journal of Clinical Neuroscience 16 (2009) 44–50 www.elsevier.com/locate/jocn

Clinical Study

Changes in cognition and health-related quality of life with unilateral thalamotomy for Parkinsonian tremor Sunita R. Nijhawan a, Sarah J.L. Banks a, Tipu Z. Aziz b,c, Ioannis Panourias d, Ralph Gregory c, John Yianni c, Simon Parkin c, Carole Joint d, Richard B. Scott a,c,* a

Department of Clinical Neuropsychology, Russell-Cairns Unit, Radcliffe Infirmary, Woodstock Road, Oxford, OX2 6HE, UK b Department of Neurological Surgery, Radcliffe Infirmary, Oxford, UK c Oxford Movement Disorder Group, Radcliffe Infirmary, Oxford, UK d Department of Neurosurgery, University Hospital of Larissa, Thessalia, Greece Received 4 February 2008; accepted 21 March 2008

Abstract Cognitive functioning and health-related quality of life were assessed pre- and post-operatively in a consecutive series of 31 Parkinson’s disease patients who underwent stereotactic unilateral thalamotomy (22 left-sided, 9 right-sided) for tremor alleviation. Neuropsychological functions assessed included verbal and visual memory, language and speech production, verbal and non-verbal reasoning, and attention and working memory. Health-related quality of life measures included both general and disease-specific questionnaires. We found a statistically significant post-operative decline in phonetic verbal fluency scores for left-operated patients, as well as improvements in self-ratings of stigma and bodily discomfort on the disease-specific quality of life questionnaire. These findings suggest that thalamotomy, when indicated, has limited cognitive sequelae and may result in improved quality of life in areas specific to Parkinson’s disease. Ó 2008 Elsevier Ltd. All rights reserved. Keywords: Parkinson’s disease; Tremor; Thalamotomy; Cognition; Health-related quality of life

1. Introduction Several studies have considered cognitive effects of stereotactic thalamotomy and electrical stimulation in individuals with Parkinson’s disease (PD). Earlier studies suggested post-operative impairment in verbal intellect, verbal memory, and language following left-sided surgery.1–8 Right-sided operations have generally been associated with fewer residual deficits,1,2,7 though visuoperceptual,9 motor coordination and integration problems3,10 have been described. Visual hemi-inattention has been demonstrated in left-sided and right-sided operations, with the former more impaired.10 Difficulties with earlier studies included variability in assessment measures, and in the size and specificity of the surgical lesions produced. *

Corresponding author. Tel.: +44 1 865 224264; fax: +44 1 865 224141. E-mail address: [email protected] (R.B. Scott).

0967-5868/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2008.03.008

More recent studies of stereotactic thalamotomy have not demonstrated extensive post-operative cognitive impairment.11–13 A review paper concluded there is no laterality effect associated with thalamotomy, except for dichotically-presented speech sounds.14 In PD, multiple sclerosis, and essential tremor patients, reduced semantic verbal fluency was found following left-sided operation for thalamotomy and thalamic stimulation, which was related to reduced speed of word production.15 Longer-term cognitive effects are unclear; though some studies followed patients up to four years post-operatively, samples were small, and most included follow-up from a few weeks to a several months. From a non-surgical standpoint, cognitive impairments in individuals with PD relative to healthy controls are well-documented,11,12 including verbal fluency deficits.16 The literature regarding health-related quality of life (HRQOL) and thalamotomy with PD patients is limited.

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An early study reported post-operative mood elevation, alongside improved somatic anxiety and agitation.4 More recently, in a 6-month follow-up of PD patients after unilateral thalamotomy, significant post-operative improvements in several dimensions on the Parkinson’s Disease Questionnaire-39 PDQ-3917 were found, including mobility, activities of daily living, emotional well-being, stigma, tremor, and rigidity.18 In another study, quality of life in PD patients who underwent neurosurgical treatment for tremor (including unilateral thalamotomy, unilateral and bilateral pallidotomy, subthalamic nucleus lesions, mixed lesions, and subthalamic nucleus stimulation) was investigated. Though comparisons between different surgical procedures were unreliable due to differences in patient characteristics and selection, significant improvements in most areas of the Short Form-36 (SF-36)19 were found; on mobility, stigma, and bodily discomfort of the PDQ39, significant improvements were also observed.20 1.1. Research questions A neuropsychological test battery and measures of HRQOL were administered at baseline and post-operatively to a consecutive series of clinical PD patients who underwent unilateral stereotactic thalamotomy (aimed at the ventrointermediate nucleus) for tremor. The psychometric assessment protocol is part of the routine pre-operative and post-operative clinical assessment for movement disorder patients in this department. HRQOL was examined using a disease-specific and two general health-related measures. The objective was to investigate archival data for pre-operative and post-operative changes in cognitive function and HRQOL in this consecutive series of clinical patients. 2. Methods 2.1. Patients and study design A within-groups investigation was used to assess differences in cognitive and HRQOL scores pre-operatively and post-operatively of a consecutive clinical series of 31 advanced PD patients (25 males and 6 females) undergoing unilateral thalamotomy for the alleviation of severe, medication-resistant tremor, from 1994 to 1999. No patients in the series satisfied criteria for dementia or any Axis I or II disorders of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV).21 Left-operated and rightoperated patients were analysed both as a group and separately (on the neuropsychological measures) for comparison. Patients were evaluated on the cognitive and HRQOL measures pre-operatively, at baseline, and on average 5.6 months (range 3–13 months) post-operatively. Longer-term neurological follow-up was also completed; mean follow-up was 31 months (range 6–60). All patients were right-handed. Twenty-two (71%) patients had a leftsided and nine (29%) a right-sided surgical procedure. No

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patients were included who had undergone bilateral operations. 2.2. Surgical technique After detailed explanations of the risks and potential benefits of the procedure, written informed consent was obtained from each patient. Details of the surgical technique have been published elsewhere.22 The nucleus ventralis intermedius of the thalamus (Vim) was targeted with neuroanatomic localisation using Image FusionTM (Image Fusion Systems Research, Beavercreek, OH, USA) and StereoPlanTM software (Integra Radionics, Burlington, MA, USA) to localise the target by fusing the patient’s pre-operative brain MRI to the intra-operative stereotactic CT scan. Intra-operatively, the target was confirmed with macrostimulation by means of a 1.8 mm diameter probe with a 2.0 mm exposed tip. With the patient awake, a RadionicsTM electrode was passed stereotactically down to the target. When stimulation confirmed the arrest of tremor, the electrode was used to make a lesion at the target nucleus. All patients underwent post-operative MRI to detect adverse sequelae such as haemorrhage and to confirm lesion placement. 2.3. Neuropsychological assessment protocol The assessment protocol used is routinely administered in the Oxford Movement Disorder Group for clinical evaluation of movement disorder patients who undergo functional neurosurgery, and includes a semi-structured clinical interview.23,24 It includes, among others, the following tests: categorical verbal fluency; phonetic verbal fluency; articulation rate; vocabulary, similarities, and digit span from the Wechsler Adult Intelligence Scale – Revised (WAIS–R); Raven’s Standard Progressive Matrices (SPM); the Stroop Colour–Word Test (CWT) (colour-word switching score used for analysis); list-learning and story memory from the Adult Memory and Information Processing Battery (AMIPB); and the words and faces subtests from the Recognition Memory Test (RMT). In a small group of patients, additional tests were available that were considered separately, mainly investigating other areas of visuo-spatial ability, information processing speed, visual memory, and bimanual dexterity.23,24 These included: the Medical College of Georgia (MCG) complex figures; the Judgement of Line Orientation test (JOLO); the Bells test of spatial neglect; the Symbol Digit Modalities Test (SDMT); and Annett’s Pegboard (including the dominant and non-dominant hands). Where available, at the post-operative assessment, parallel forms of tests were used. For some patients, because of environmental, geographical, motivational, timing, or other factors, it was not possible to complete the full protocol; in addition, because of the time period over which the patients were studied (5 years), there were some variations in the clinical protocol.

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HRQOL was examined using a disease-specific, self-rated questionnaire, the PDQ-39, and two general measures, the SF-36 (self-rated) and the Functional Limitations Profile (FLP; UK version of the USA Sickness Impact Profile), including both the self-rated and carer-rated versions for the FLP.25 The PDQ-39 is sensitive to quality of life for PD patients; the more generic health and disability measures, the SF-36 and the FLP, have been used reliably with a variety of medical conditions. A semi-structured clinical interview and a screening questionnaire, the Hospital Anxiety and Depression Scale (HADS),26 were also included in the assessment. The HADS is a valid and reliable instrument often used for investigating psychological and emotional difficulties in individuals with health-related problems. 2.4. Statistical analysis The score used for analysis depended on the statistical test; raw scores, standard scores, age-scaled scores, and Z-scores were considered as appropriate. Most of our data were not normally distributed because of outliers and intratest score variability, particularly on cognitive measures. Thus, data were primarily analysed using non-parametric measures. For the cognitive tests, left-operated and rightoperated patients were first analysed together, then considered separately; for the quality of life measures, the sample was analysed as a whole. To determine within-groups preoperative and post-operative test performance differences on the assessment measures, Wilcoxon Signed Rank Tests were used. Median scores and interquartile ranges were reported rather than means and standard deviations (SD) for most measures, which were more appropriate due to the non-normal test score distribution. Comparisons between groups were evaluated using the Mann-Whitney Test. Spearman correlations were used to investigate relationships between depression and quality of life. To address missing values in the data, we used pairwise exclusion procedures. A conservative significance level (p = 0.01) was adopted to reduce Type 1 errors. However, results that

were significant at p = 0.05 significance level were considered to indicate other trends. 3. Results 3.1. Patient characteristics Demographic information for the patient sample is included in Table 1. All patients included were right-handed. There was no significant difference in mean age between left-operated and right-operated patients. Mean time since initial diagnosis of PD was 6.6 years (range 1–15). From a cognitive standpoint, in this series, there was a wide range of intellectual abilities. At the pre-operative stage, a portion of the sample (n = 10) had an ‘average’ premorbid estimated verbal intelligence quotient (IQ) on the National Adult Reading Test (NART) (median = 100.50; interquartile range 19.75; range 75–122). We administered three subtests (vocabulary, similarities, digit span) from the WAISR to most patients to calculate an estimated baseline verbal IQ, with a median of 100.00 (interquartile range 17.70; range 72–125). The patient group’s baseline scores on the range of tests included in the battery, including verbal fluency, verbal and visual memory, attention and executive functioning, and visuo-spatial skills, mostly fell within the ‘‘low average” to ‘‘average” range relative to age-matched normative data. There was, however, notable variability in scores, with minimum scores up to 2–3 SDs below normative data in some cases. Eight patients’ scores met ‘‘caseness” criteria for the anxiety subscale and 9 for depression on the HADS (i.e. score P8–10), though as noted, no patients met DSM-IV diagnostic criteria for an anxiety or depressive disorder either pre-operatively or post-operatively. 3.2. Neurological and neurosurgical outcome The main indication for surgery in all patients was disabling upper limb Parkinsonian tremor resistant to medical

Table 1 Demographic and clinical presentation of the total patient sample Patient characteristics

Pre-operative

Post-operative

Mean age (years) Mean time since PD diagnosis (years) Median verbal IQ* Median non-verbal IQ** HADS depression ‘‘caseness”*** HADS anxiety ‘‘caseness” Mean Hoehn & Yahr ‘‘on” Mean Hoehn & Yahr ‘‘off” Mean UPDRS (parts 2) ‘‘on” Mean UPDRS (parts 3) ‘‘on” Mean UPDRS (parts 2) ‘‘off” Mean UPDRS (parts 3) ‘‘off”

62.8 (range 38–81) 6.6 (range 1–15) 100.00 (range 72–125) (interquartile range 17.70) 104.00 (range 75–130) (interquartile range 24.00) 8 9 2.4 2.8 9 19 16.9 38

NA NA 103.00 (range 78–123) (interquartile range 17.10) 107.00 (range 75–130) (interquartile range 24.00) 8 11 2.2 2.8 7 18.1 15.5 29.8

IQ = intelligence quotient, NA = not applicable, UPDRS = Unified Parkinson’s Disease Rating Scale. Based on a formula using the WAIS-R vocabulary, similarities, and digit span subtest scores. ** Using the Raven’s Standard Progressive Matrices (SPM). *** p < 0.01; ‘‘caseness” = score P 8–10 on the Hospital Anxiety and Depression Scale (HADS). subscales. *

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therapy. A consultant neurologist and neuropsychologist confirmed diagnosis and suitability for surgery. Surgery for this series of patients was performed by the same neurosurgeon. Unified Parkinson’s Disease Rating Scale27 and Hoehn and Yahr28 ratings were obtained (Table 1), but as tremor was the principal motor deficit in this patient series, patient neurosurgical outcome was primarily evaluated by assessing tremor status employing the Bain (0–10) Analogue Tremor Rating Scale.29 There were no peri-operative deaths. Two patients suffered persistent neurological deficit, mild hemiparesis in one and dysarthria in both. In these patients the latest recorded tremor status was used. Mean neurological follow-up was 31 months (range 6–60). Following unilateral

Table 2 Pre-operative and post-operative tremor ratings (Bain Analogue Tremor Rating Scale) Tremor rating

Pre-operative % of patients

Post-operative % of patients

0 1 2 3 4 5 6 7 8 9 10

0 0 0 0 0 6.5 22.6 29.0 41.9 0 0

64.5 6.5 9.7 16.1 0 3.2 0 0 0 0 0

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thalamotomy, contralateral tremor was absent in 20 patients (64.5%) and was reduced to a rating of 63 in a further 10 patients (32.3%) (Table 2). 3.3. Cognition Table 3 shows the neuropsychological assessment results for all patients. Post-operatively, there were trends toward improvement in immediate (p = 0.014) and delayed recall (p = 0.024) performance on the AMIPB Story. There was also a trend showing decline in phonetic verbal fluency (p = 0.035). The separate psychometric results for the left-operated (n = 22) and right-operated (n = 9) patients are presented in Table 4. Pre-operatively, there were no significant differences on any cognitive measures between left- and right-operated patients, though there was a general trend for higher scores in the left-operated patients. For the right-operated patients, no findings were significant; there was a trend showing improvement on the immediate recall of the AMIPB List-Learning task (p = 0.051). The left-operated patients showed a significant reduction in phonetic verbal fluency (p = 0.002). Consistent with the overall group trend, there was a small, non-significant improvement in the AMIPB Story immediate recall (p = 0.042). There was also a small decrease in Digit Span score (p = 0.038). To investigate further possible reasons for the decrease in verbal fluency, a ‘‘verbal speed factor”, examining the speed of verbal output, was developed. The scores for Articulation rate, categorical verbal fluency, phonetic verbal fluency, and the SDMT – oral scores were converted

Table 3 Pre-operative and post-operative psychometric test scores for all patients Psychometric testsb

Pre-operative

Post-operative

Verbal Categorical fluency (Animals) Phonetic fluency (FAS) Articulation rate WAIS–R Vocabulary* WAIS–R Similarities*

16.00 40.00 10.50 10.00 10.00

15.00 39.00 10.83 10.00 10.00

Visuo-spatial Raven’s SPM Attention–Executive WAIS–R Digit Span* Stroop CWT** Memory AMIPB Story IR** AMIPB Story DR** AMIPB List Learning** AMIPB List DR** RMT Words* RMT Faces*

(8.00; 9 to 33) (18.00; 15 to 71) (3.34; 6.33 to 15.83) (5.00; 6 to 15) (3.50; 5 to 14)

(6.00; 8 to 33) (15.00; 13 to 58)a (2.71; 6.50 to 14.30) (4.00; 7 to 16) (3.00; 6 to 14)

34.00 (19.00; 13 to 49)

36.00 (23.00; 15 to 52)

10.00 (3.00; 5 to 15) 0.76 (2.60; 3.81 to 6.47)

10.00 (3.00; 6 to 16) 0.98 (1.44; 3.22 to 6.08)

0.56 0.84 0.80 0.68 12.50 8.00

0.36 0.66 0.52 0.69 11.00 9.00

(1.04; 2.53 to (1.48; 2.94 to (1.44; 2.94 to (1.15; 2.68 to (5.75; 4 to 16) (6.25; 3 to 17)

1.68) 1.90) 0.87) 1.90)

(2.02; 1.53 to (1.72; 1.57 to (1.68; 2.94 to (0.99; 2.76 to (5.25; 3 to 16) (5.25; 4 to 17)

2.30)a 2.17)a 1.88) 1.88)

Raw scores except where * denotes age-scaled scores and ** Z-scores. Values are median (interquartile range; range). AMIPB = Adult Memory and Information Processing Battery, CWT = Colour–Word Test, FAS = FAS task standard scores for phonetic fluency, RMT = Recognition Memory Test, SPM = Standard Progressive Matrices, WAIS-R = Wechsler Adult Intelligence Scale – Revised. a p < 0.05; IR = immediate recall; DR = delayed recall. b Verbal fluency, Raven’s, Digit Span, AMIPB Story, n = 31; Similarities, AMIPB List, n = 29; Articulation rate, n = 28; Vocabulary, n = 27; RMT Words and Faces, n = 26; Stroop, n = 25.

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Table 4 Pre-operative and post-operative psychometric test scores for left-operated and right-operated patients Psychometric tests

Pre–operative a

Post–operative b

Right 15.00 34.00 9.75 9.00 9.00

Verbal Categorical fluency (Animals) Phonetic fluency (FAS) Articulation rate WAIS–R Vocabulary* WAIS–R Similarities*

Left 18.00 40.50 11.42 10.00 10.00

Visuo-spatial Raven’s SPM

34.00 (21.25)

27.00 (18.00)

Attention–Executive WAIS-R Digit Span* Stroop CWT**

10.50 (4.25) 0.33 (2.71)

10.00 (2.00) 1.25 (1.52)

Memory AMIPB Story IR** AMIPB Story DR** AMIPB List Learning** AMIPB List DR** RMT Words* RMT Faces*

0.22 0.40 0.67 0.38 13.00 9.00

(8.50) (18.75) (3.84) (6.00) (3.75)

(0.98) (1.65) (1.25) (1.22) (3.00) (7.00)

0.87 1.01 1.43 1.00 8.00 8.00

(6.50) (20.00) (2.47) (2.00) (3.00)

(1.07) (1.04) (1.42) (1.29) (9.00) (6.00)

Left 14.50 33.00 10.92 11.00 10.50

(7.00) (16.00)    (2.38) (4.00) (3.75)

38.00 (18.00) 9.50 (4.00)   0.82 (1.87) 0.22 0.01 0.73 0.69 11.00 11.00

(2.25)   (2.10) (1.67) (0.94) (5.00) (6.00)

Right 16.00 42.00 9.25 10.00 10.00

(6.50) (5.50) (2.96) (3.00) (2.50)

24.00 (20.00) 11.00 (3.50) 1.52 (1.47) 0.57 0.96 0.41 1.03 10.00 8.00

(0.81) (0.71) (1.91) (1.73) (6.00) (3.00)

Raw scores except where * denotes age-scaled scores and ** Z-scores. Values are median (interquartile range).   p < 0.05;    p < 0.01; IR = immediate recall; DR = delayed recall. AMIPB = Adult Memory and Information Processing Battery, CWT = Colour–Word Test, FAS = FAS task standard scores for phonetic fluency, RMT = Recognition Memory Test, SPM = Standard Progressive Matrices, WAIS-R = Wechsler Adult Intelligence Scale – Revised, a Verbal fluency, Raven’s, Digit Span, AMIPB story, n = 22; Articulation rate, Similarities, AMIPB List, n = 20; Vocabulary, RMT Words and Faces, n = 19; Stroop, n = 18. b Verbal fluency, Similarities, Raven’s, Digit Span, AMIPB Story and List, n = 9; Articulation rate, Vocabulary, n = 8; Stroop, RMT Words and Faces, n = 7.

to items produced per minute, and the mean of these scores used to produce the speed factor; pre-operative and postoperative test scores were available for 16 patients (8 leftoperated, 8 right-operated). There was no significant difference on this factor for the full patient sample preoperatively and post-operatively, nor were there any significant differences either pre-operatively or post-operatively on separate analysis of left-operated and right-operated patients. With respect to results of the additional cognitive tests, including domains of visuo-spatial ability, processing speed and dexterity, visual attention, and visual memory, completed in a small subgroup (n = 16; 8 left-operated, 8 right-operated) of the overall patient sample, there were no significant pre-operative differences between left-operated and right-operated patients. When all patients were included for analysis, there was a trend toward decreased performance on the MCG copy (p = 0.029). For rightoperated patients only, the decrease in performance on the MCG copy just missed significance (p = 0.017), and accounted for most of the change for the overall group. There were no other notable changes in performance pre-operatively and post-operatively on these additional tests. 3.4. Health-Related Quality of Life For the HRQOL measures, the left-operated and rightoperated patients were analysed together as a group. No significant changes were found in the overall dimensions

or the subscales on either the patient-rated or carer-rated FLP. There was significant improvement in the SF-36 Change in Health rating (p = 0.001), with general improvement on other areas of this questionnaire. Several elements of the PDQ-39 also improved, with bodily discomfort (p = 0.001), stigma (p = 0.001), and activities of daily living (p = 0.007) reaching significance. Despite these improvements in overall HRQOL, 8 of 30 patients still met ‘‘caseness” for anxiety on the HADS and 11 for depression; again, no patients met DSM-IV diagnostic criteria for any Axis I or II disorder. There were no significant changes in median pre-operative and post-operative anxiety or depression scores, which were well within normal limits, for the sample as a whole. Given that the relationship between depression and HRQOL in PD is well-established,30 a correlational analysis between the HADS depression scores and the HRQOL measures was also completed. Our data were broadly consistent with these established findings. Pre-operatively, on the HRQOL questionnaires, there were no significant differences between the left-operated and the right-operated patients on the SF-36. On the FLP, the right-operated patients tended to rate themselves as more disabled than the left-operated individuals; the difference between the two groups neared significance for the mobility subsection (Z = 2.54, p = 0.011). In addition, on the PDQ-39, the difference between the groups neared significance for stigma (Z = 2.39, p = 0.017), with the rightoperated group endorsing a higher level of problems.

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4. Discussion Overall, this study demonstrated specific cognitive deficits related to the side of surgical intervention. Phonetic verbal fluency declined following left-sided surgery and copying a complex geometric figure following right-sided surgery. In addition to verbal and visuo-spatial demands, both of these tasks also involve a frontal or executive element; phonetic fluency requires initiation, retrieval, and generation of verbal information, while the geometric copy involves planning and organisation. Taken together, this may suggest that unilateral thalamotomy can produce disruptions in the neuroanatomical pathways between subcortical areas and the prefrontal cortex, resulting in subtle increased post-operative executive dysfunction. Such deficits may be manifest in either verbally or visuo-spatially mediated tasks, dependent upon the side of surgery. These findings are in contrast to some more recent studies, which have suggested that whereas PD patients function significantly below normal pre-operatively, including areas of language, memory, and executive function, thalamotomy does not further impair cognitive function,11–13 though verbal fluency was not included in one study.11 One review concluded that there is no laterality effect associated with the side of the thalamotomy procedure, except for the use of dichotically presented simple speech sounds, in which reduced right-ear advantage following left-sided lesions was found.14 Semantic verbal fluency was reduced in 62 PD, multiple sclerosis, and essential tremor patients in a study that followed both left-sided thalamotomy and thalamic stimulation. Neuropsychological evaluations were completed at baseline and 6 months following surgery. Minimal change in other areas of cognitive function (e.g. attention and executive function, naming, verbal and visual memory), and visuospatial function was observed. A decrease in the speed of verbal production may have accounted for the observed decline in verbal fluency; slowed reading on the Stroop CWT was also found, though the interference score was intact.15 We also wondered whether verbal speed might be reduced post-operatively. However, this was not supported in our analysis of a ‘‘verbal speed factor”, including measures of fluency, articulation rate, and the oral version of the SDMT, in which we found no significant changes pre-operatively and post-operatively. Our findings showed a small, but non-significant decline for both left-operated and right-operated patients on the switching portion of the Stroop CWT, which is more sensitive to executive function. This would be consistent with more frontal deficits as discussed earlier. There was no evidence of significant premorbid deficit or post-operative change in more crystallized verbal abilities that would suggest more broad-ranging verbal impairment. In absolute (i.e. raw score) terms, the changes observed in all areas of cognitive functioning were small, and would reflect little clinical or functional significance; indeed, despite these specific areas of cognitive decline, all HRQOL measures generally showed improvement. Enhanced HRQOL was seen particularly on the PDQ-39, the disease-specific

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questionnaire, in terms of daily living, stigma, and bodily discomfort. From a neurological standpoint, 97% of patients showed long-term tremor suppression to a variable degree, on average nearly 3 years post-operatively. Limited information in the literature discusses quality of life in PD following thalamotomy; however, the available information has generally been positive, also demonstrating post-operative improvements on general measures of quality of life4,20 and on the PDQ-39.18,20 Our results were consistent with this literature. More recently, deep brain thalamic stimulation has increasingly become the treatment of choice over ablative stereotactic neurosurgery, because of the decreased risk of adverse events and the reversible nature of the intervention; stimulation also does not appear to be associated with significant cognitive sequelae and may allow greater improvement in functional abilities.15,31 Thalamotomy does, however, remain a useful course of treatment for patients with disabling tremor when the patient is elderly, dislikes the idea of an electrical stimulator, if there is a predicted difficulty for the patient to cope with the stimulator, or if there is a proximal arm and/or leg tremor.30 To our knowledge, this is one of few studies that considers both cognitive function and HRQOL in PD patients who have undergone unilateral stereotactic thalamotomy. Our results suggest mild post-operative cognitive impairment, as well as improvements in specific, disease-related factors of quality of life. These selective findings in HRQOL generally map onto the clinical characteristics of this patient group, who present for treatment with unilateral, disabling tremor, often accompanied by complaints of social embarrassment and stigma. Limitations of our study lie in the small sample size, and in the lack of a healthy, age-matched control group for pre-operative comparison. In addition, because of the time scale over which the patients were evaluated (5 years), some changes in the neuropsychological assessment protocol resulted in not all tests being available for analysis for the entire sample. It would be important to investigate further any longterm and lasting differences in cognitive sequelae and HRQOL between thalamic stimulation and thalamotomy. Based upon the results in the literature, it would seem valuable to include measures of both semantic and phonetic verbal fluency, and verbal speed and production, as well as additional tests of executive function to better delineate any observed post-operative deficits. Additional investigations of HRQOL in larger patient samples, including both generic and disease-specific measures, would also be useful to more sensitively and effectively assess post-operative change and to identify the most relevant areas for outcome and management. Acknowledgements We wish to thank Charlotte Boulton and Joanna Wilson, Assistant Psychologists, for assistance with psychometric assessment and data entry.

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