Parkinson Disease: Gross RE

Gross RE. · Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30022, USA. · Neurotherapeutics. · Pubmed #18394570 No free full text.

Abstract: Fifteen years after its resurrection, pallidotomy for Parkinson's disease (PD) and dystonia has once again been supplanted, this time by deep brain stimulation (DBS). Did this occur because pallidotomy was not effective or safe, or because DBS was found to be more effective and safer? This review focuses on the evidence-and its quality-supporting the effectiveness and safety of pallidotomy for PD and dystonia, and the comparative effectiveness and safety of DBS of the subthalamic nucleus (STN) and globus pallidus pars interna (GPi). Discussed first are the determinants of "level 1" recommendations, including the confounding effects on interpretation of randomized clinical trials (RCTs) that fail to control for patient bias (i.e., placebo effects). Although several RCTs have been performed comparing unilateral pallidotomy to medical therapy, GPi DBS, or STN DBS for PD, none controlled for patient bias. Comparison of these trials to estimate the placebo effect, and examination of retrospective case series, suggests that the true effectiveness of unilateral pallidotomy is 20% to 30% reduction of 'off' total motor UPDRS scores, which is similar to the effects of unilateral GPi DBS or STN DBS, but less than bilateral STN DBS. At experienced centers, safety of unilateral pallidotomy appears equivalent to unilateral DBS, but bilateral DBS is likely safer than bilateral pallidotomy. Whereas there have been no RCTs of pallidotomy for dystonia, two double-blind, sham-controlled RCTs of bilateral GPi DBS were performed. Nevertheless, limited uncontrolled series suggest that bilateral pallidotomy is similar to GPi DBS in effectiveness and safety for dystonia. Thus, pallidotomy was not rejected because of lack of effectiveness or safety, and it remains a viable alternative in situations where DBS is not available or not feasible.

Gross RE, Krack P, Rodriguez-Oroz MC, Rezai AR, Benabid AL. · Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA. · Mov Disord. · Pubmed #16810720 No free full text.

Abstract: The vast majority of centers use electrophysiological mapping techniques to finalize target selection during the implantation of deep brain stimulation (DBS) leads for the treatment of Parkinson's disease and tremor. This review discusses the techniques used for physiological mapping and addresses the questions of how various mapping strategies modify target selection and outcome following subthalamic nucleus (STN), globus pallidus internus (GPi), and ventralis intermedius (Vim) deep brain stimulation. Mapping strategies vary greatly across centers, but can be broadly categorized into those that use microelectrode or semimicroelectrode techniques to optimize position prior to implantation and macrostimulation through a macroelectrode or the DBS lead, and those that rely solely on macrostimulation and its threshold for clinical effects (benefits and side effects). Microelectrode criteria for implantation into the STN or GPi include length of the nucleus recorded, presence of movement-responsive neurons, and/or distance from the borders with adjacent structures. However, the threshold for the production of clinical benefits relative to side effects is, in most centers, the final, and sometimes only, determinant of DBS electrode position. Macrostimulation techniques for mapping, the utility of microelectrode mapping is reflected in its modification of electrode position in 17% to 87% of patients undergoing STN DBS, with average target adjustments of 1 to 4 mm. Nevertheless, with the absence of class I data, and in consideration of the large number of variables that impact clinical outcome, it is not possible to conclude that one technique is superior to the other in so far as motor Unified Parkinson's Disease Rating Scale outcome is concerned. Moreover, mapping technique is only one out of many variables that determine the outcome. The increase in surgical risk of intracranial hemorrhage correlated to the number of microelectrode trajectories must be considered against the risk of suboptimal benefits related to omission of this technique.

Gross RE, Lozano AM. · Department of Neurosurgery, University of Utah Health Sciences Center, Salt Lake City 84132, USA. · Neurol Res. · Pubmed #10769817 No free full text.

Abstract: In just 12 years since its introduction, deep brain stimulation (DBS) has become well established as a safe and effective therapy in the treatment of medically refractory movement disorders. Ventralis intermedius (Vim) DBS has virtually replaced thalamotomy in the routine clinical treatment of essential tremor, affording relief to thousands of patients who previously would not have undergone surgery, and there is increasing usage of Vim DBS in other tremors of intention (e.g., multiple sclerosis). Subthalamic nucleus (STN) and globus pallidus internus (GPi) DBS have revolutionized the treatment of advanced stage Parkinson's disease, improving all cardinal disease features and increasing 'on' time without dyskinesias. Finally, DBS of various sub-cortical structures is being developed and tested in other less prevalent movement disorders such as dystonia. Future developments in this rapidly advancing area will no doubt include widening indications for this relatively safe surgical procedure, elucidation of the mechanisms of action of electrical stimulation, and technological advancements improving effectiveness and convenience.

Lang AE, Duff J, Saint-Cyr JA, Trepanier L, Gross RE, Lombardi W, Montgomery E, Hutchinson W, Lozano AM. · The Division of Neurology, Dept. of Medicine, The Toronto Western Hospital, 399 Bathurst St., MP-11, Toronto, Ontario, M5T 2S8, Canada. · J Neurol. · Pubmed #10526000 No free full text.

Abstract: There has been a resurgence in the use of functional neurosurgery for Parkinson's disease. An important factor that has played a role in this development is the recent understanding of the functional anatomy of the basal ganglia including a knowledge of the changes in the activities of neurons in the internal segment of the globus pallidus (Gpi) and the subthalamic nucleus (STN) in Parkinson's disease as well as the knowledge of the presence of segregated functional loops within the basal ganglia which include a sensory-motor loop that involves the posteromedial globus pallidus rather than the anterior GPi where earlier pallidotomy lesions had been made. Laitinen reintroduced the modern posteroventral medial pallidotomy (PVMP) in 1992. Since then it has become clear that this treatment has major effects on levodopa-induced dyskinesias and, unlike Vim thalamotomy, improves bradykinesia and rigidity as well as tremor. In this report, we review a number of topics related to PVMP including the clinical results of pallidotomy available in the literature as well as an update of our own 2 year follow-up data, studies evaluating factors that might predict the subsequent response to pallidotomy, the neuropsychological effects of the procedure, results of imaging studies including the correlation of clinical effects with lesion location, the question of bilateral pallidotomy and pallidotomy combined with deep brain stimulation and finally whether PVMP is effective in other parkinsonian disorders.

Honey C, Gross RE, Lozano AM. · Department of Surgery, University of British Columbia, Canada. · Can J Neurol Sci. · Pubmed #10451760 No free full text.

Abstract: Despite optimization of medical therapy, a large number of patients with Parkinson's disease continue to be disabled. For this group, alternate treatment strategies such as neurosurgical intervention can be considered. Recent advances in neurosurgical techniques and in understanding the pathophysiology of motor disturbances in PD have made surgery safer and more effective. Functional neurosurgical procedures to lesion or electrically modulate dysfunctional basal ganglia circuits or to protect or restore dopaminergic transmission are being increasingly used. These procedures are having a profound impact on the motor disturbances of PD and are producing important improvements in quality of life of patients.

Gross RE, Lombardi WJ, Lang AE, Duff J, Hutchison WD, Saint-Cyr JA, Tasker RR, Lozano AM. · Department of Surgery, University of Toronto, The Toronto Hospital, Ontario, Canada. · Brain. · Pubmed #10094250 links to  free full text

Abstract: The purpose of this study was to examine the relationship between lesion location and clinical outcome following globus pallidus internus (GPi) pallidotomy for advanced Parkinson's disease. Thirty-three patients were prospectively studied with extensive neurological examinations before and at 6 and 12 months following microelectrode-guided pallidotomy. Lesion location was characterized using volumetric MRI. The position of lesions within the posteroventral region of the GPi was measured, from anteromedial to posterolateral along an axis parallel to the internal capsule. To relate lesion position to clinical outcome, hierarchical multiple regression analysis was used. The variance in outcome measures that was related to preoperative scores and lesion volume was first calculated, and then the remaining variance attributable to lesion location was determined. Lesion location along the anteromedial-to-posterolateral axis within the GPi influenced the variance in total score on the Unified Parkinson's Disease Rating Scale in the postoperative 'off' period, and in 'on' period dyskinesia scores. Within the posteroventral GPi, anteromedial lesions were associated with greater improvement in 'off' period contralateral rigidity and 'on' period dyskinesia, whereas more centrally located lesions correlated with better postoperative scores of contralateral akinesia and postural instability/gait disturbance. Improvement in contralateral tremor was weakly related to lesion location, being greater with posterolateral lesions. We conclude that improvement in specific motor signs in Parkinson's disease following pallidotomy is related to lesion position within the posteroventral GPi. These findings are consistent with the known segregated but parallel organization of specific motor circuits in the basal ganglia, and may explain the variability in clinical outcome after pallidotomy and therefore have important therapeutic implications.

Machado A, Rezai AR, Kopell BH, Gross RE, Sharan AD, Benabid AL. · Center for Neurological Restoration, Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Mov Disord. · Pubmed #16810722 No free full text.

Abstract: Deep brain stimulation (DBS) is a widely accepted therapy for medically refractory Parkinson's disease (PD). Both globus pallidus internus (GPi) and subthalamic nucleus (STN) stimulation are safe and effective in improving the symptoms of PD and reducing dyskinesias. STN DBS is the most commonly performed surgery for PD as compared to GPi DBS. Ventral intermediate nucleus (Vim) DBS is infrequently used as an alternative for tremor predominant PD patients. Patient selection is critical in achieving good outcomes. Differential diagnosis should be emphasized as well as neurological and nonneurological comorbidities. Good response to a levodopa challenge is an important predictor of favorable long-term outcomes. The DBS surgery is typically performed in an awake patient and involves stereotactic frame application, CT/MRI imaging, anatomical targeting, physiological confirmation, and implantation of the DBS lead and pulse generator. Anatomical targeting consists of direct visualization of the target in MR images, formula-derived coordinates based on the anterior and posterior commissures, and reformatted anatomical stereotactic atlases. Physiological verification is achieved most commonly via microelectrode recording followed by implantation of the DBS lead and intraoperative test stimulation to assess benefits and side effects. The various aspects of DBS surgery will be presented.

Rezai AR, Kopell BH, Gross RE, Vitek JL, Sharan AD, Limousin P, Benabid AL. · Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Mov Disord. · Pubmed #16810673 No free full text.

Abstract: Numerous factors need to be taken into account when implanting deep brain stimulation (DBS) systems into patients with Parkinson's disease. The surgical procedure itself can be divided into immediate preoperative, intraoperative, and immediate postoperative phases. Preoperative considerations include medication withdrawal issues, stereotactic equipment choices, imaging modalities, and targeting strategy. Intraoperative considerations focus on methods for physiological confirmation of a given target for DBS electrode deployment. Terms such as microelectrode recording, microstimulation, and macrostimulation will be defined to clarify inconsistencies in the literature. Advantages and disadvantages of each technique will be addressed. Furthermore, operative decisions such as staging, choice of electrode and implantable pulse generator, and methods of device fixation will be outlined. Postoperative issues include imaging considerations, including magnetic resonance safety, device-device interactions, and immediate surgical complications pertaining to the DBS procedure. This report outlines answers to a series of questions developed to address all aspects of the DBS surgical procedure and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society. It outlines answers to a series of questions developed to address all surgical aspects of deep brain stimulation.

Abosch A, Gross RE. · Department of Neurosurgery, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia, USA. · Clin Neurosurg. · Pubmed #15571158 No free full text.

This publication has no abstract.

Lombardi WJ, Woolston DJ, Roberts JW, Gross RE. · Department of Neurosurgery, University of Utah, Salt Lake City 84132, USA. · Neurology. · Pubmed #11552004 No free full text.

Abstract: OBJECTIVE: To assess cognitive and affective functioning in patients with essential tremor (ET). BACKGROUND: ET is traditionally thought to occur in isolation, without other neurologic abnormalities or cognitive changes. Recent evidence of gait disturbance and bradykinesia in these patients suggests that the neurologic abnormalities in ET may be more widespread than was once thought. Cognitive function in these patients has not been the subject of in-depth study. METHODS: Cognitive performance and mood were assessed in 18 consecutive patients with ET and 18 consecutive patients with PD who visited the neurosurgical clinic for surgical treatment of their symptoms. RESULTS: The patients with ET were found to have deficits on tests of verbal fluency, naming, mental set-shifting, verbal memory, and working memory, as well as higher levels of depression. In contrast to these areas of deficit, their performance was better than that of the normative sample on several tests of verbal and nonverbal conceptualization and reasoning. Tremor severity was not correlated with cognitive deficits. Patients with PD had deficits on the same tests that were impaired in the ET group and on tests of visuospatial processes. Direct comparison of the ET and PD groups showed greater impairment in facial perception in the PD group and greater impairment in verbal fluency and working memory in the ET group. CONCLUSION: Patients with ET have deficits in specific aspects of neuropsychological functioning, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests involvement of frontocerebellar circuits in this disease.

Lombardi WJ, Gross RE, Trepanier LL, Lang AE, Lozano AM, Saint-Cyr JA. · Department of Neurosurgery, University of Utah, Salt Lake City, UT 84132, USA. · Brain. · Pubmed #10734006 links to  free full text

Abstract: Current models of basal ganglia anatomy posit the existence of multiple parallel, anatomically segregated circuits. Anatomical data from non-human primates suggest that the circuits subserving motor functions are segregated from those subserving cognitive functions. Here we present data that demonstrate that, in humans, motor and cognitive frontosubcortical circuits are segregated. We studied a group of patients with Parkinson's disease undergoing surgical lesioning of the globus pallidus internus for relief of their symptoms. Lesion location along an anteromedial-to-posterolateral axis was found to be related to postsurgical outcome on both cognitive and motor measures. Performance on several neuropsychological measures, including the generation of category exemplars and continuous mental addition, was linearly related to distance along this axis, with anteromedial lesions leading to postsurgical impairment, intermediate lesions having little effect and posterolateral lesions leading to an improvement on several measures. The same relationship was found between memory performance under conditions of proactive interference and lesion location within the globus pallidus internus. In contrast, bradykinesia, assessed as the speed of finger-tapping, had a non-linear relationship to lesion location, intermediate lesions leading to greater postsurgical improvement than lesions in more extreme anteromedial or posterolateral locations. These data demonstrate that the cognitive effects of pallidotomy can be dissociated from the motor effects. These effects depend upon the placement of the lesions within the globus pallidus internus, supporting the segregation of functionally distinct circuits in the human pallidum.

Gross RE, Lombardi WJ, Hutchison WD, Narula S, Saint-Cyr JA, Dostrovsky JO, Tasker RR, Lang AE, Lozano AM. · Department of Surgery, University of Toronto, Ontario, Canada. · J Neurosurg. · Pubmed #10067915 No free full text.

Abstract: OBJECT: To understand the factors that determine the distribution of lesions after microelectrode-guided pallidotomy for Parkinson's disease, the authors quantitatively characterized lesion location in a cohort of patients who were prospectively followed to determine the effects of pallidotomy on clinical outcome. METHODS: Thirty-three patients underwent volumetric magnetic resonance (MR) imaging after surgery to allow quantitative lesion localization in relation to conventional intraventricular landmarks and, alternatively, more anatomically relevant landmarks. The validity of the method was verified in a cohort of postpallidotomy patients who underwent concurrent volumetric and stereotactic MR imaging in an external head frame. Lesions were distributed over a considerable distance in the anteroposterior (8.8 mm) and mediolateral (8.7 mm) dimensions in relation to the anterior commissure and wall of the third ventricle, respectively. Less variation was seen in lesion location in the dorsoventral dimension (4.8 mm) in relation to the intercommissural plane. CONCLUSIONS: Lesion distribution was not random: lesion locations in the anteroposterior and mediolateral dimensions were highly correlated, such that lesions were distributed from anteromedial to posterolateral, parallel to the border of the globus pallidus internus with the obliquely oriented internal capsule. The factors that led to variability in lesion location were variation in third ventricle width and the oblique anteromedial-to-posterolateral course of the internal capsule. This demonstration of variability of lesion location in a cohort of patients who experienced excellent clinical benefits and minimal postoperative complications emphasizes the importance of anatomical variations in determining lesion position and the need for physiological corroboration for correct lesion placement.

Gross RE. · Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA. · Stereotact Funct Neurosurg. · Pubmed #18477863 No free full text.

This publication has no abstract.