Neuropsychological, neurological and functional outcome following pallidotomy for Parkinson's disease. A consecutive series of eight simultaneous bilateral and twelve unilateral procedures.

Brain (1998), 121, 659–675 Neuropsychological, neurological and functional outcome following pallidotomy for Parkinson’s disease A consecutive series of eight simultaneous bilateral and twelve unilateral procedures Richard Scott, Ralph Gregory, Nic Hines, Camille Carroll, Nigel Hyman, Vakis Papanasstasiou, Cathy Leather, Jeremy Rowe, Peter Silburn and Tipu Aziz Oxford Movement Disorder Group, Department of Neurological Surgery, Radcliffe Infirmary, Oxford, UK Summary Intellectual, psychological and functional outcomes were evaluated in a consecutive series of 20 Parkinsonian patients who had unilateral (UPVP) or simultaneous bilateral posteroventral pallidotomy (BPVP) using Image FusionTM and StereoplanTM (Radionics Inc., Boston, Mass., USA) with stimulation for lesion localization. Comprehensive baseline and 3-month postoperative neuropsychological and neurological assessment protocols were administered together with questionnaire measures of functional disability, quality of life and psychological symptomatology. Changes in patients’ clinical presentation and scores on psychometric tests, questionnaires and observational rating scales were then examined. We observed no new neuropsychiatric sequelae directly related to pallidotomy. Cognitive sequelae were restricted to selective reductions in categorical verbal fluency following UPVP (P , 0.001) and BPVP (P , 0.01) and a Correspondence to: R. B. Scott, Russell-Cairns Unit, Radcliffe Infirmary, Oxford OX2 6HE, UK reduction in phonemic verbal fluency following BPVP (P , 0.01); these changes were not reported subjectively. A fall in diadochokinetic rates (P , 0.01) and some subjective reports of a worsening in pre-existing dysarthria, hypophonia and hypersalivation/drooling following BPVP also suggested changes in speech motor apparatus; however, these changes did not have significant functional consequences. There was one case of more generalized cognitive impairment following BPVP. We also observed significant symptomatic improvement on neurological rating scales; following UPVP, Total Unified Parkinson’s Disease Rating Scale (UPDRS) scores improved by 27% (P , 0.01) and following BPVP the improvement was 53% (P , 0.05). Patients’ perceptions of reduced postoperative functional disability and improvements in ‘quality of life’ also achieved statistical significance on a number of both physical and psychosocial questionnaire subscales. Keywords: pallidotomy; cognition; outcome; Parkinson’s disease Abbreviations: BPVP 5 bilateral posteroventral pallidotomy; DSM-IV 5 Diagnostic and Statistical Manual of Mental Disorders, 4th edition; FLP 5 Functional Limitations Profile; H&Y 5 Hoehn and Yahr; HADS 5 Hospital Anxiety and Depression Scale; MPTP 5 1-methyl 4-phenyl 6-tetrahydropyridine; PDQ-39 5 Parkinson’s Disease Questionnaire; PVP 5 posteroventral pallidotomy; S&E 5 Schwab and England Activities of Daily Living Scale; SF-36 5 Medical Outcomes Study Short Form; UPDRS 5 Unified Parkinson’s Disease Rating Scale; UPVP 5 unilateral posteroventral pallidotomy Introduction Disenchantment with the long-term side effects and response fluctuations of medical therapy has led to a re-evaluation of the role of surgery in the management of Parkinson’s disease (Goetz and Diederich, 1996; Olanow 1996; Obeso et al., 1997). Laitinen’s reintroduction of Leksell’s pallidotomy © Oxford University Press 1998 (Laitinen et al., 1992) coincided with the development of a deeper understanding of the neural mechanisms underlying Parkinson’s disease symptoms, largely from experimental studies on the MPTP-exposed parkinsonian primate (Bergman, 1990; Aziz et al., 1991). Briefly stated, this model 660 R. Scott et al. suggests that loss of nigrostriatal dopamine leads to excessive putaminal inhibition of the lateral pallidum; this releases the subthalamic nucleus from inhibitory regulation, and this in turn excessively drives the posteroventral pallidum to inhibit the motor thalamus. However, many questions remain unanswered regarding the role of pallidotomy in the treatment of Parkinson’s disease. Despite reports from a number of different centres on the procedure’s clinical efficacy (Dogali et al., 1995; Iacono et al., 1995b; Laitinen, 1995; Lozano et al., 1995; Baron et al., 1996) and the neurophysiological mechanisms putatively involved (Dogali et al., 1994; Grafton et al., 1995; Iacono et al., 1995a; Eidelberg et al., 1996; Obeso et al., 1997), scepticism about the net clinical benefit of pallidotomy remains. There may be several reasons for this, including unacceptably high (i.e. 40%) complication rates reported at some centres (Sutton et al., 1995), a lack of consensus regarding the optimal lesion size/site and/or surgical technique [i.e. microelectro-guided versus macrostimulation; staged versus simultaneous bilateral posteroventral pallidotomy (BPVP)] (Bakay et al., 1992; Friedman et al., 1996) or perhaps an intuitive difficulty accepting that selectively lesioning the brain can be beneficial in a progressive neurodegenerative disease. However, a lack of confidence in the timing, scope and objectivity of reported measures of clinical outcome and their ability to identify any occult deficits may also be an important factor. The potential complexity of evaluating net benefit following pallidotomy is daunting in a progressive, multisystem disease with considerable variability both within and between individuals (Kelly, 1995). Potential costs to the patient include known surgical complications. Iacono et al. (1995b) have reported visual field defects, hemiparesis, intracranial abscess and subcortical and intrapallidal haemorrhage, with an overall complication rate of 6.3% (later resolving to 3.2%); in addition, postoperative dysarthria, facial weakness, confusion (Baron et al., 1996), sexual disinhibition (Dogali et al., 1995) and depression (Sutton et al., 1995) have all been observed. There have also been reports in the early literature of language deficits, albeit illdefined. For example, Leksell’s group (Svennilson et al., 1960) observed word-finding difficulties and paraphasias in 24% of patients with lesions in the dominant hemisphere. Other studies noted spoken language deficits (Cooper and Bravo, 1958; Gillingham et al., 1960; Allan et al., 1966); however, the outcome from thalamotomy and pallidotomy was not differentiated in these series. The posteroventral pallidum is not known to be implicated in cognition or mood, but until the recent pilot study of outcome following unilateral posteroventral pallidotomy (UPVP) by Baron et al. (1996) there had been no reported attempts to systematically screen these domains. This is a significant oversight with an ablative procedure that demands precise targeting and perhaps optimal lesion volume and contour. There have been no reports of cognitive or psychiatric outcome following simultaneous BPVP. With some exceptions (Laitinen et al., 1992; Laitinen, 1994; Baron et al., 1996), most publish (...truncated)