Health-Related Quality of Life in Parkinson's Disease after Pallidotomy and Deep Brain Stimulation

Brain and Cognition 42, 399–416 (2000) doi:10.1006/brcg.1999.1112, available online at http://www.idealibrary.com on

Health-Related Quality of Life in Parkinson’s Disease after Pallidotomy and Deep Brain Stimulation Kristy Straits-Tro¨ster,*,† Julie A. Fields,† Steven B. Wilkinson,‡ Rajesh Pahwa,† Kelly E. Lyons,† William C. Koller,† and Alexander I. Tro¨ster† *Department of Veterans Affairs Medical Center, †Department of Neurology, and ‡Division of Neurosurgery, University of Kansas Medical Center This study explored the multidimensional outcome of three neurosurgical interventions for Parkinson’s disease (PD): pallidotomy (N ⫽ 23), pallidal deep brain stimulation (DBS) (N ⫽ 9), and thalamic DBS (N ⫽ 7). All patients completed the Sickness Impact Profile (SIP) and the Beck Depression Inventory. Pallidotomy patients also completed the Profile of Mood States, the Beck Anxiety Inventory, and a disease-specific quality of life (QOL) measure, the Parkinson’s Disease Questionnaire (PDQ-39). Three months after surgery, all neurosurgical groups showed significant improvements in mood and function, including physical, psychosocial, and overall functioning. Pallidal DBS and pallidotomy patients who completed additional QOL measures reported decreased anxiety and tension, increased vigor, improved mobility and ability to perform activities of daily living, and decreased perceived stigma. Psychosocial dysfunction scores from the SIP were related to depressed mood both at baseline (r ⫽ .42) and at followup (r ⫽ .45), but the physical dysfunction subscale was not related to mood at either time point, suggesting that disruption of social relationships due to PD may have more impact on affective distress than physical symptoms alone. Results suggest that neurosurgical interventions for PD improve disabling PD motor symptoms and also improve several domains of quality of life.  2000 Academic Press

INTRODUCTION

The evaluation of treatments for Parkinson’s disease (PD) produces a sizable challenge for clinical researchers. First, treatments are highly diverse Portions of this study were presented at the Twenty-Sixth Annual International Neuropsychological Society Meeting, in Honolulu, Hawaii, and the Nineteenth Annual Meeting of the Society of Behavioral Medicine, in New Orleans, Louisiana. We appreciate the help of Jennifer Kieltyka for assistance with patient recruitment and evaluation and acknowledge the courage and commitment of our participants. Address correspondence and reprint requests to Kristy Straits-Tro¨ster, DVAMC Kansas City, 4801 E. Linwood Blvd. (116-B), Kansas City, MO 64128. Fax: (816) 861-1110. E-mail: [email protected]. 399 0278-2626/00 $35.00 Copyright  2000 by Academic Press All rights of reproduction in any form reserved.

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and may include pharmacotherapy, pallidotomy, thalamotomy, deep brain stimulation (DBS) of the globus pallidus, thalamus, and subthalamic nucleus, or combinations of these approaches. Second, some of the treatments are symptom-specific, and comparisons across interventions are difficult. Each procedure or combination of procedures is indicated by the predominant PD symptomatology, which may vary considerably both within and between individuals, and may be complicated by treatment-related fluctuations (i.e., the on–off phenomenon) and time of day relation to ingestion of meals and medications (Lang, 1995). Third, all interventions involve some element of risk, some known (e.g., risk of bleeding in surgery) and others unknown (e.g., long-term impact on cognition or affect). Thus multidimensional and longitudinal assessment of outcome is important, particularly when evaluating novel or experimental treatments which may have both beneficial or adverse effects not anticipated. In addition to disabling motor symptoms such as tremor, rigidity, bradykinesia, and postural instability, which may occur intermittently and increase when the patient is concentrating or feeling anxious, PD patients report considerable fatigue and increased isolation related to difficulties with activities of daily living and communication, which may result in perceived social stigma (Knight, Godfrey, & Shelton, 1988). Many PD patients are embarrassed by their symptoms and may become apathetic, bored, and lonely, as they progressively give up their social roles due to physical disability (Singer, 1974a). The corresponding health, social, and economic consequences of PD have been well documented (Chrischilles et al., 1998; Dakof & Mendelsohn, 1986; Martinez-Martin, 1998; Singer, 1973, 1974a;) and may impact mood and perceived quality of life. Thus, treatment efforts have targeted the motor symptoms associated with PD, and improvements in health-related quality of life have been expected to follow decreased motoric symptomatology, as noted generally with the advent of levodopa therapy (Singer, 1974b). Over time, adverse effects of levodopa have been identified across all stages of the disease continuum. Potential adverse effects of levodopa therapies include peak-dose dyskinesias, nausea and vomiting, postural hypotension, and fluctuations in motor function and mental status (Koller, 1994). These adverse effects and limitations in the effectiveness of long-term pharmacotherapy, such as end-of-dose deterioration, combined with the natural progression of disease, have led to consideration of alternative treatments and a return to further development of neurosurgical interventions for PD (Clarke, Zobkiw, & Gullaksen, 1995). These efforts have been further fueled by technologic advances, supportive evidence from animal studies (Bergman, Wichmann, & DeLong, 1990), and improved understanding of basal ganglia functions (Goetz & Diederich, 1996; Bondi & Tro¨ster, 1997). The evaluation of treatment effectiveness for PD has traditionally consisted of clinician ratings of patient motor symptoms, such as on the Hoehn

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and Yahr scale (Hoehn & Yahr, 1967). The development of the Unified Parkinson’s Disease Rating Scale (UPDRS: Fahn, Elton, & Members of the UPDRS Development Committee, 1987) introduced a more comprehensive approach to clinician assessment and addressed patient mentation, mood, and behavioral changes in addition to motor function. Clinical trials have increasingly begun to utilize patient ratings of health-related quality of life (HRQOL) (Wilson & Cleary, 1995). The systematic evaluation of the patient’s subjective perception of outcome in addition to more traditional ‘‘objective’’ measures of outcome, such as severity of observable symptoms, is consistent with the World Health Organization’s multidimensional definition of health and its efforts to develop valid and reliable QOL assessment tools (WHOQOL Group, 1998). Although measures differ as to specific aspects of HRQOL assessed, most conceptual models suggest that at least four domains are central to quality of life, including physical health, psychological function, social relationships, and environment (Wilson, Goetz, & Stebbins, 1996; WHOQOL Group, 1998). The broad impact of neurologic illness on cognitive function and regulation of affect and its social ramifications, such as stigma and isolation, suggest that patient-perceived HRQOL may be a key consideration in assessing outcome or effectiveness of treatments for Parkinson’s disease and other movement disorders (Tro¨ster, Lyons, & Straits-Tro¨ster, 1999). The examination of health-related quality of life outcome following neurosurgical interventions for Parkinson’s disease is novel and evolving, and only three such studies have been published as of this writing. Baron et al. (1996) reported significant improvements in all cardinal parkinsonian motor signs after posterior internal pallidal ablation (Gpi pallidotomy) in their pilot study of 15 medically intractable PD patients (mean Total UPDRS scores improved 30.1% at 3-month followup), and mean Total UPDRS scores remained improved at 6-month and 1-year followup assessments. The UPDRS Motor Examination ‘‘off ’’ subscale score improved 24.9%, and mean Motor improvement was maintained at 6 and 12 months. Quality of life scores on the Medical Outcomes Scale (MOS) indicated significant improvement in physical functioning, social functioning, and vitality. No post surgical changes were noted in emotional functioning, neuropsychological performance (once patients with complications were excluded), or psychiatric status. Positive QOL changes were maintained over 1 year, and the authors concluded that pallidotomy is a highly effective treatment for patients with advanced PD. Narabayashi and colleagues (1997) examined the effects of posteroventral pallidotomy (PVP), combined with an additional small thalamic lesion, on motor symptoms and scores on the Minnesota Multiphasic Personality Inventory (MMPI) among 12 PD patients. They reported marked improvement in rigidity and tremor in all but 1 patient, to the degree that tremor and rigidity were almost totally alleviated on the side contralateral to surgery. Consistent with Baron et al. (1996), functional outcomes included

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improvements in stooped posture, decreased masking of the facies, increased speech volume and clarity, and improved voluntary fine motor movements. Walking became easier, smoother, and more balanced and approached normal parameters on the side contralateral to surgery. Intellectual functioning as assessed by a translated version of the Wechsler Adult Intelligence Scale (WAIS) did not change post-surgery. Although HRQOL per se was not assessed, the patients’ scores on scales 1, 2, and 3 of the MMPI decreased significantly at postoperative followup (which ranged from 8 to 15 months). These reduced scale elevations were interpreted as evidence of a reduction in preoccupation and worry about one’s illness and physical symptoms (scale 1, Hypochondriasis), decrease in depressed mood, sadness and pessimism (scale 2, Depression), and decrease in rapid mood changes, exaggerated affect, and egocentricity (scale 3, Hysteria). Because these are the three scales most likely to be elevated among patients with chronic progressive illness, the reduction in these scores postoperatively probably represents the relief and optimism associated with decreased motor symptomatology and may reflect improved quality of life. Within the same study, changes observed in MMPI scale scores among an additional group of 8 patients who received thalamotomy only (no PVP) were not statistically significant. Scott and colleagues (1998) reported multidimensional outcome results for 20 consecutive patients receiving posteroventral pallidotomy (PVP), including 8 bilateral and 12 unilateral procedures. They point out that the neglect of systematic assessment of cognitive and psychiatric outcome following a procedure such as pallidotomy, which requires precise targeting of lesions and for which optimal lesion characteristics are unknown, is a significant oversight. Their patients completed multidisciplinary assessment protocols 4 weeks before surgery and 3–4 months postoperatively, with minimal changes in medications. Mean Total UPDRS scores indicated 53% improvement for the bilateral PVP patients and 38% improvement for the unilateral PVP patients, with some improvement noted in contralateral tremor. The effect on tremor was not as predictable as that for dyskinesias. No significant group changes were observed on a neuropsychological battery, including over 25 psychometric tests, except for a decline in verbal fluency scores. Pallidotomy patients as a group reported improved quality of life, reduced functional disability, and reduced anxiety and depression. These changes were evident both on a global QOL measure (SF-36), which indicated significant improvements in physical and social functioning, bodily pain, and energy–vitality postoperatively, and on a PD symptom-specific QOL measure, the Parkinson’s Disease Questionnaire (PDQ-39: Jenkinson, Fitzpatrick, & Peto, 1998). Improvements in activities of daily living, mobility, and bodily discomfort on the PDQ-39 were statistically significant, and improvements in emotional well-being and stigma approached significance (N ⫽ 13). In these three PVP outcome studies, the authors concluded that pallidotomy appears to be effective in reducing rigidity and drug-induced dyskine-

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sias, with mild improvements noted for tremor. Improvements were observed in fine and gross motor function, resulting in better ability to ambulate safely and communicate (both writing and speech), improved mood and energy levels, decreased anxiety and depressive symptoms, and improved appetite, sleep patterns, and libido. Preliminary results of pallidal deep brain stimulation (DBS) indicate improvements in cardinal PD symptoms without significant negative cognitive effects (Pahwa et al., 1997; Tro¨ster et al., 1997a). Thalamotomy appears best suited for essential tremor, with some role possible in tremor-predominant PD (Narabayashi et al.,1997; Koller et al., 1998). Thalamic stimulation of the ventral intramediate (VIM) nucleus has been reported to be as effective as thalamotomy and is associated with fewer adverse effects, such as dysarthria (Lyons et al., 1998; Busenbark et al., 1996), and cognitive deficits (Tro¨ster et al., 1997b; Koller et al., 1998). Because neurosurgical interventions do carry a certain level of risk (i.e., 5% series complication rate, Scott et al., 1998), comprehensive assessment of outcome is indicated to assist the patient and provider in making informed treatment decisions. Several sites have begun using the Sickness Impact Profile (SIP: Bergner et al., 1981) to identify patterns in outcomes following microelectrode-guided pallidotomy or implantation of thalamic or subthalamic deep brain stimulators (Shale et al., 1997; Busenbark et al., 1996), while others have used subscales of the UPDRS (ADL score) to indicate QOL outcome (Moro et al., 1998) or are in the process of developing their own PD symptom-specific QOL measures (Glosser et al., 1997; Welsh et al., 1997). A combination of general QOL functional assessment and PD symptom-specific outcome may be helpful in providing a means both to compare PD patients with other medical patient groups, and to more sensitively assess PD-specific treatment outcomes. The purpose of this study was to examine the HRQOL treatment outcomes of three neurosurgical interventions for Parkinson’s disease: pallidotomy, pallidal DBS, and thalamic DBS. In addition to traditional observer-rated motor symptom ratings, patient perceptions of their quality of life were examined using psychometrically sound measures. Variables of interest included multiple domains of physical and psychosocial functioning, mood, and PD-specific QOL issues such as perceived stigma. We sought to answer the following research questions: (1) Do neurosurgical interventions for PD decrease motor disability and increase HRQOL? (2) Is physical dysfunction related to mood disturbance in patients with medically intractable PD? METHODS

Participants Patients attending the Movement Disorders clinic at an academic medical center (University of Kansas) were diagnosed with idiopathic Parkinson’s disease (PD), according to standard

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TABLE 1 Demographic Variable Means and Standard Deviations (SD) by Treatment Group Variables

Pallidotomy

N Age** Education Age at Onset** Age at Diagnosis** Duration* Postsurgery Interval** (months)

23 62.7 (7.5) 13.0 (2.8) 47.4 (7.2) 48.7 (7.1) 14.0 (6.4) c 3.7 (1.1)

Pallidal DBS 50.3 14.1 36.0 39.8 10.3 2.6

9 (13.0) a (3.6) (10.1) a (10.1) b (4.9) (.88) 1

Thalamic DBS 65.1 13.7 54.0 57.1 8.0 4.4

7 (12.0) (1.9) (17.0) (12.0) (3.8) (1.3)

Pallidal DBS ⬍ Pallidotomy, Thalamic DBS (SNK: Student’s–Newman–Keul’s test). Pallidal DBS ⬍ Pallidotomy ⬍ Thalamic DBS (SNK test). c SNK posthoc test not significant. * p ⬍ .05. ** p ⬍ .01, one-way ANOVA. a b

criteria (at least two of three cardinal signs: tremor, rigidity, bradykinesia, and levodopa responsiveness). Patients with PD considered for neurosurgical interventions experienced symptoms refractory to medications and/or intolerable side effects from medications. All treatment groups completed a core group of psychosocial measures, and pallidotomy patients completed supplemental measures. The mean interval from surgery to postsurgical comprehensive assessment was 3.6 months. Patients selected for pallidotomy and pallidal DBS experienced disabling end-of-dose motor fluctuations and/or peak-dose dyskinesias. Pallidal DBS patients were younger than those in the other two treatment groups and were younger at first onset of symptoms and at time of PD diagnosis (see Table 1). Patients with tremor-predominant PD were selected for thalamic DBS and were older at PD symptom onset and diagnosis. PD patients with dementia, severe major depression, hallucinations, history of prior neurosurgical procedures, unstable medical conditions (including cardiac pacemakers), or conditions requiring MRI were not eligible for inclusion in this study. Patient gender, handedness, and side of neurosurgical procedure are listed in Table 2.

Neurosurgical procedures: Surgical procedures utilized have been described in detail elsewhere (Burns,Wilkinson, Kieltyka et al., 1997), and only brief summaries are presented here. Pallidotomy. Under local anesthesia, a burr hole was made and a microelectrode was inserted above the level of the optic tract and ventral to the globus pallidus interna (Gpi). The patients rested in a semirecumbent position with head tilted forward, and Gelfoam was packed into the TABLE 2 Categorical Demographic Variables by Treatment Group Variable

Pallidotomy

Pallidal DBS

Thalamic DBS

Gender Handedness Side of surgery

11 M, 12 F 20 R, 3 L 9 R, 14 L

6 M, 3 F 8 R, 1 L 3 R, 6 L

6 M, 1 F 7 R, 0 L 3 R, 4 L

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opening after insertion of the electrode to decrease loss of cerebrospinal fluid. The amplitude, frequency, and pattern of action potentials were recorded and mapping was completed such that the optic tract was avoided, and cellular targets associated with motor movement in the most affected extremities were identified as optimal lesion targets. Once they were defined, the microelectrode was replaced by a thermocoupled temperature monitoring and lesion electrode, and three to six discrete lesions were produced. (see Burns et al., 1997, for details). Pallidal DBS. Initial target coordinates within the Gpi were determined from CT of the head after placement of a stereotactic head ring under local anesthesia. Microelectrode recording and stimulation techniques were used to refine target location, and macroelectrode stimulation was then used to determine effects of stimulation on vision, speech, and strength and sensation in limbs contralateral to the side of the implantation. The quadripolar DBS electrode (Medtronics, Inc.) was positioned where macroelectrode stimulation did not produce visual field or hemisensory loss or hemiparesis. Stimulation with the DBS electrode was used to determine its final placement. It was then connected subcutaneously to a pulse generator implanted in the tissue of the subclavicular region (Tro¨ster et al., 1997a). Postoperative stimulator parameters were adjusted to optimize positive effect while minimizing side effects (see Pahwa et al., 1997, for more details). Thalamic DBS. Similar to the technique described for pallidal DBS, a burr hole was placed under local anesthetic, and an electrode was inserted into the brain. At several levels above and below the calculated target, electrical stimulation was initiated to provoke contralateral arm and face paresthesias and then to determine the effect of stimulation on tremor. The optimal location for the DBS electrode was defined as that where stimulation at the lowest voltage produced transient parasthesias and good tremor control, but no motor or speech deficits (Tro¨ster et al., 1997b). The Medtronics DBS electrode was positioned in this location, and the pulse generator was implanted subcutaneously and connected with the DBS electrode. Stimulation parameters were optimized and further adjusted on subsequent outpatient visits.

Outcome Assessment Measures: The motor score of the UPDRS (Fahn et al., 1987) was obtained for all neurosurgical candidates before and after surgery. UPDRS Motor scores obtained closest to time of psychosocial and neuropsychological assessment were selected for this study. Pallidotomy patients’ UPDRS scores were obtained in the off-medication condition pre and postsurgery, whereas pallidal DBS patients were assessed on-medications at baseline and on-stimulator/on-medications at followup. Thalamic DBS patients’ UPDRS scores were obtained off-medications at baseline and on stimulator/off-medications at followup. Motor outcomes are presented separately for each neurosurgical procedure in Table 3. Mood measures included: the Beck Depression Inventory (BDI: Beck & Steer, 1993), which has been shown to be an effective, reliable indicator of depressed mood in PD patients (Levin, Llabre, & Weiner, 1988); the Beck Anxiety Inventory (BAI: Beck & Steer, 1990); and the Profile of Mood States (POMS: McNair, Lorr & Droppelman, 1971). The POMS yields scaled scores for Depression–Dejection, Tension–Anxiety, Anger–Hostility, Fatigue–Vigor, Energy–Inertia, and Confusion–Bewilderment and has been shown to be a reliable and valid measure of mood states in older adults (Gibson, 1997). HRQOL measures included (1) the Sickness Impact Profile (SIP: Bergner, Bobbitt, Carter, & Gilson, 1981), a generic measure of functional impairment validated in many groups of medical patients, including PD (Longstreth, Nelson, Linde, & Munoz, 1992), which yields scores for Physical, Psychosocial, and Total Impairment and 12 subscale scores and (2) the Parkinson’s Disease Questionnaire (PDQ-39: Jenkinson, Fitzpatrick & Peto, 1998), a PD-specific QOL measure that was developed from in-depth interviews with PD patients and has demonstrated good reliability and validity (Peto, Jenkinson, Fitzpatrick, & Greenhall, 1995; Peto, Jenkinson, & Fitzpatrick, 1998).

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TABLE 3 Patient Scores at Baseline and 3-Month Followup for Motor Dysfunction (UPDRS), Affective Distress, and Health-Related Quality of Life by Treatment Group Treatment group

Variable

Pallidotomy a

UPDRS

N ⫽ 23

SIP PHYS SIP PSYCH SIP TOTAL BDI BAI

Pallidal DBS b

Baseline mean (SD)

Postsurgery followup

41.0 (15.6) Off meds 26.2 (15.0) 32.5 (16.4) 28.3 (11.9) 14.8 (10.6) 20.7 (7.7)

29.1 (18.2) Off meds 14.8 (15.6) 20.8 (15.2) 18.2 (13.2) 9.8 (7.6) 15.4 (10.2)

UPDRS

29.33 (13.7) On meds

N⫽9

SIP PHYS SIP PSYCH SIP TOTAL BDI BAI

23.3 21.1 21.6 9.9 18.2

20.11 (9.2) On meds/ On stimulation 9.4 (7.2) 12.4 (10.5) 10.9 (8.8) 7.0 (5.9) 11.9 (6.4)

Thalamic DBS b

UPDRS c

47.43 (18.0) Off meds

N⫽7

SIP PHYS SIP PSYCH SIP TOTAL BDI

10.8 13.8 14.1 7.7

(12.0) (3.0) (9.0) (5.9) (7.5)

(8.2) (11.5) (7.6) (4.6)

38.14 (16.5) Off meds/ On stimulation 9.1 (7.0) 12.7 (11.2) 13.0 (7.1) 10.0 (8.5)

Level of significance .000 .000 .000 .000 .094 .103 .066

.008 .086 .021 .067 .007 .018

.735 .612 .735 .655

Note. Abbreviations used: UPDRS, Unified Parkinsons Disease Rating Scale; SIP, Sickness Impact Profile; PHYS, Physical Impairment Scale; PSYCH, Psychosocial Impairment Scale; TOT, Total Impairment Scale; BDI, Beck Depression Inventory; BAI, Beck Anxiety Inventory. a Paired t test, two-tailed tests. b Wilcoxon signed ranks test, two-tailed tests. c UPDRS motor scores were obtained according to each of the three intervention protocols.

RESULTS

Changes in Motor Dysfunction and HRQOL Presurgical and 3-month postoperative scores are presented in Table 3. Paired t tests (two-tailed) were performed to test significance of differences in pre- and postoperative scores in the pallidotomy group (N ⫽ 23). Nonparametric tests (Wilcoxon signed-ranks tests) were utilized to assess pre- and postsurgical differences in the pallidal DBS (N ⫽ 9) and thalamic DBS (N ⫽ 7) treatment groups, due to small sample sizes and nonnormal data distributions.

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FIG. 1. Parkinson’s Disease Quality of Life Questionnaire (PDQ-39) subscale scores at baseline and 3 months postpallidotomy (N ⫽ 11). Higher scores indicate poorer function. Scale names: Activities of Daily Living, Body Discomfort, Cognitions, Emotional Well-Being, Communication, Mobility, Social Support, and Stigma. **p ⬍ .001, two-tailed paired t tests.

Pallidotomy. Mean UPDRS Motor scores (off-condition) improved 29% after unilateral PVP. This improvement is comparable to the 24.9% improvement in mean UPDRS Motor score reported by the Emory University group post-PVP (Baron et al., 1996). The 43.8% Motor score improvement reported by Scott et al. (1998) represents combined results from both bilateral and unilateral pallidotomies. Significant improvements in Physical, Psychosocial, and Total functioning (SIP) were reported postoperatively, and lower scores on depression and anxiety measures indicated a trend for patients to report less affective distress at followup (see Table 3). PD-specific symptoms also improved (PDQ-39), as illustrated in Fig. 1. Although only changes in Activities of Daily Living (ADLs) and Mobility reached statistical significance in the subset of pallidotomy patients administered this instrument (N ⫽ 11; PDQ-39 was not available when initial patients were assessed), most subscales changed in the anticipated direction of improvement. Pallidal DBS. Mean UPDRS Motor scores were improved 31.4% postoperatively in the optimized on-stimulator/on-medications condition. This experimental procedure was associated with improved Physical and Total functioning (SIP) and significantly decreased anxiety postoperatively. A trend was noted for improved Psychosocial functioning (SIP) and decreased depression (BDI). Thalamic DBS. Mean UPDRS Motor scores improved 9.3% postoperatively. Although the global Motor score does not emphasize the desired tremor-specific effects exclusively, it should be noted that these scores were

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FIG. 2. Sickness Impact Profile (SIP) scores at baseline and 3 months postsurgical intervention across all treatment groups. ***p ⬍ .001, two-tailed t tests.

obtained in the off-medication condition preoperatively and on-stimulator/ off-medications condition postoperatively, which should reflect maximal contrast in pre–post scores. No significant changes were observed in HRQOL (SIP) or depressed mood (BDI) postoperatively. Analysis of the Sickness Impact Profile: Changes in SIP scores were in the hypothesized direction of improvement across all three treatment groups, although small sample sizes in the DBS groups may have precluded detection of statistical significance in differences observed on some scales. SIP scores were combined across pallidotomy, pallidal DBS, and thalamic DBS groups to obtain more power in detection of an overall postsurgical effect on HRQOL. Lower SIP scores postoperatively indicated improvement in the HRQOL domains of Physical, Psychosocial, and Total functioning, as illustrated in Fig. 2. SIP subscales were examined separately by neurosurgical treatment group to allow observation of patterns of changes associated with specific treatments (see Fig. 3). Changes in subscale scores on the SIP for pallidotomy and pallidal DBS reveal striking improvements for Ambulation, Mobility, and Independent Body Care and Movement, which make up the Physical Dysfunction Scale. Such improvements in activities of daily living (ADLs) were expected to coincide with significant motor improvements. Smaller improvements were noted post-thalamic DBS, commensurate with smaller changes in motor scores in this patient group. Interestingly, sizable improve-

FIG. 3. Mean SIP subscale scores at baseline and 3 months postsurgical intervention by treatment group. Higher scores indicate more problems in area of function. A, Ambulation; M, Mobility; BCM, Body Care and Movement (Physical Dimension); SI, Social Interaction; AB, Alertness Behavior; EB, Emotional Behavior; C, Communication (Psychosocial Dimension); SR, Sleep/Rest; E, Eating; W, Work; HM, Home Management; RP, Recreation/ Pastimes (Independent Categories).

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ments were also noted for Social Interaction, Alertness Behavior, and Emotional Behavior for both the pallidotomy and pallidal DBS groups, but not for the thalamic DBS group. Pallidotomy and thalamic DBS patients reported improvement in Communication, an SIP subscale which taps writing (two items) and speech difficulties (seven items). Overall Effects of Neurosurgical Interventions on Mood Patients who completed the Profile of Mood States (N ⫽ 11; introduced to the study with the PDQ-39) reported significantly improved Vigor at followup (t ⫽ 2.47; p ⬍ .05). Significant improvements were also noted for depressed mood (BDI) (t ⫽ ⫺2.0; p ⬍ .05), and anxiety (BAI) (t ⫽ ⫺3.69; p ⬍ .01). Correlation of Motor Dysfunction and HRQOL In order to address the second research question, the relationships among HRQOL, mood, and motor function were examined among all patients with medically intractable PD undergoing assessment for neurosurgical intervention (N ⫽ 39). Pearson product–moment correlations were calculated for baseline and 3-month followup scores on the UPDRS Motor scale, SIP primary scales, and Beck Anxiety and Depression Inventories. Level of motor dysfunction was highly related to anxiety at baseline (r ⫽ .64; p ⬍ .01), but was not related to quality of life, as assessed by the SIP. However, BDI scores at baseline were significantly related to Psychosocial functioning on the SIP both at baseline and followup, suggesting a robust relationship between depressed mood and social/emotional functioning, both pre- and postsurgery (see Table 4). DISCUSSION

Neurosurgical interventions for PD appear to effectively decrease motor symptoms and are associated with improved quality of life. In this study, treatment effects were most strongly evidenced for unilateral posteroventoral pallidotomy. Improvements in UPDRS motor scores were comparable to those reported by others for unilateral pallidotomy (Baron et al., 1996). Improved technology in microelectrode-guided stereotaxic neurosurgery is probably a key factor in better outcomes and reduced complications in comparison to initial classical pallidotomy (Laitinen, 1995; Laitinen, Bergenheim, & Hariz, 1992). We found patient ratings of physical, psychosocial and overall impairment to be sizably reduced at 3-month postsurgery followup. Pallidotomy patients also reported feeling less depressed and anxious and having more energy 3 months after surgery. It will be important to assess these changes over time to determine whether these mood changes are sustained or perhaps reflect postsurgical relief from anticipatory anxiety.

UPDRS-pre UPDRS-post BAI-pre BAI-post BDI-pre BDI-post SIP PHYS-pre SIP PHYS-post SIP PSY-pre SIP PSY-post SIP TOT-pre SIP TOT-post

1.00 .65** .32 .54** .07 .25 .22 .29 .20 .24 .26 .34*

1 1.00 .08 .27 ⫺.36 ⫺.05 .07 .15 .01 ⫺.00 .04 .13

2

1.00 .66** .51* .65** ⫺.08 ⫺.13 .13 .15 .05 ⫺.05

3

1.00 .29 .79** .27 .14 .43* .24 .39 .21

4

1.00 .52* .04 ⫺.06 .42* .46* .26 .19

5

1.00 .29 .07 .45* .25 .44* .18

6

1.00 .62** .55** .29 .87* .50**

7

1.00 .49** .65** .61** .89**

8

1.00 .65** .86** .60**

9

1.00 .52** .90**

10

1.00 .62**

11

Note. Abbreviations used: UPDRS, Unified Parkinsons Disease Rating scale; BDI, Beck Depression Inventory; BAI, Beck Anxiety Inventory; SIP, Sickness Impact Profile; PHYS, Physical Impairment Scale; PSYCH, Psychosocial Impairment Scale; TOT, Total Impairment Scale. * p ⬍ .05. ** p ⬍ .01.

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

Variable name

TABLE 4 Correlations Among Mood and Health-Related Quality of Life as Assessed by the SIP (N ⫽ 39)

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The usefulness of the PDQ-39 as a psychometrically sound PD-specific HRQOL measure has been extended specifically to the assessment of PD neurosurgical candidates by this study. Our preliminary results from the PDQ-39 suggest that quality of life improvements postpallidotomy are evidenced in the areas rated as most important by PD patients. In addition to statistically significant reductions in problems with activities of daily living and mobility, PDQ scale scores for bodily discomfort, cognitive and communication problems, and perceived social stigma all changed in the direction of improvement. Only patients’ ratings of problems in social relationships increased slightly after surgery, but this increase was not significant. Ongoing patient enrollment may lead to more statistical power for testing the significance of changes reported postsurgery. Further, it may be helpful to assess more directly how PD symptoms and treatments affect caregivers and close personal or family relationships. Glozman, Bicheva, and Fedorova (1998) recently published a Scale of Quality of Life of Care-Givers (SQLC) which is designed to evaluate both qualitative and quantitative QOL in the areas of professional activities of the PD patient caregivers, impact on social and leisure activities, and everyday caregiving responsibilities. Confirmation of this measure’s reliability and validity, or a related measure, may lead to its use as part of a comprehensive psychosocial assessment of neurosurgical candidates and their support systems. Future studies in this area may also elucidate the relationship between mood and psychosocial functioning in PD. Pallidal DBS patients improved according to clinician-rated UPDRS motor symptoms, patient-rated QOL (SIP), and symptoms of depressed mood and anxiety (BDI, BAI). Results from this sample of nine pallidal DBS patients suggest that pallidal DBS is an effective treatment for some PD patients. It should be noted that these patients were younger, which may have made them better surgical candidates from a medical risk point of view. It is also possible that younger PD patients would report more improvement following alleviation of motor symptoms, if indeed they were initially more distressed prior to treatment. Singer (1974a) has pointed out that younger PD patients generally report higher levels of distress related to their symptoms, which can be viewed as a form of ‘‘premature aging.’’ However, in our study baseline levels of affective distress were not higher in the pallidal DBS group (between groups one-way ANOVAs for BDI and BAI not significant). In fact, both the pallidotomy and pallidal DBS patients reported decreased symptoms of anxiety and depressed mood, whereas the thalamic DBS patients showed no change in depressed mood (which was quite low at baseline). Because these procedures may impinge on neural pathways related to mood, and because more than 50% of PD patients will develop depression at some point in their disease continuum (Starkstein & Mayberg, 1993), it will be important to continue monitoring affect and psychopathology postintervention.

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Thalamic DBS patients were selected based on tremor-predominant PD symptomatology. Consistent with results reported by Tasker (1998), thalamic DBS produced improvements in tremor, suggesting that it may be effective for a subset of tremor-predominant PD patients. It may be preferable to thalamotomy due to the potential reversibility of side effects through adjustment of the stimulator, which can minimize side effects and/or optimize effectiveness (Tasker, 1998). Although this group improved in motor function (UPDRS) and tremor was reduced as expected, they did not report significant improvements on generic quality of life indices (SIP). Although there is always the possibility of Type II error in testing significance of change in such a small sample (N ⫽ 7), it is also possible tremor is not as highly related to QOL as are other movement disorder symptoms, such as bradykinesia and postural abnormalities, which are not usually improved by thalamic DBS or thalamotomy. In a survey of 211 PD patients, Lyons et al. (1997) found that postural instability and gait abnormalities were the best predictors of quality of life, explaining 36% of the variance in overall QOL score, after controlling for disease duration. Tremor and rigidity, although reported as problematic, did not enter into the regression equation. Certainly in essential tremor, in which tremor is the only disabling motor symptom, significant improvements in HRQOL have been observed (Busenbark et al., 1991, 1996). It is possible that a PD-specific HRQOL measure may have tapped more subtle changes in QOL. PD is a progressive disease, and its course following postoperative improvements is unknown. Ideally, a PD control group would best serve for comparison of changes over time (e.g., comparing slopes of change in motor function). However, medically intractable PD is devastating to patients and their families, and the assignment of such patients to a wait-list or placebo control group is fraught with ethical and practical issues. Thus, longitudinal studies may need to access archival data for comparison or initiate studies in which subjects serve as their own controls (single subject designs). Patients’ experience of Parkinson’s disease has begun to be carefully chronicled (Brod, Mendelsohn, & Roberts, 1998; Dakof & Mendelsohn, 1989), and the complexity of the relationships among disease, disability, treatment outcomes, and psychosocial contexts have only begun to be examined. REFERENCES Baron, M. S., Vitek, J. L., Bakay, R. A. E., Green, J., Kaneoke, Y., Hashimoto, T., Hashimoto, T., Turner, R. S., Woodard, J. L., Cole, S. A., McDonald, W. M., & DeLong, M. R. 1996. Treatment of advanced Parkinson’s disease by posterior Gpi pallidotomy: 1-year results of a pilot study. Annals of Neurology, 40, 355–366. Beck, A. T. & Steer, R. A. 1993. Beck Depression Inventory, Manual. San Antonio, TX: Psychological Corp. Beck, A., & Steer, R. A. 1990. Beck Anxiety Inventory, Manual. San Antonio, TX: Psychological Corp.

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