Bruce Hall

Unilateral and bilateral pallidotomy for idiopathic Parkinson's disease: a case series of 115 patients.

Lesioning of the internal pallidum is known to improve the symptoms of idiopathic Parkinsons disease (PD) and alleviate dyskinesia and motor fluctuations related to levodopa therapy. The benefit obtained contralateral to a single lesion is insufficient in some cases when symptoms are bilaterally disabling. However, reports of unacceptably high rates of adverse effects after bilateral pallidotomy have limited its use in such cases. We report on the outcome of unilateral (UPVP) and bilateral (BPVP) posteroventral pallidotomy in a consecutive case series of 115 patients with PD in the United Kingdom and Australia. After 3 months, UPVP resulted in a 27% reduction in the off medication Part III (motor) Unified Parkinsons Disease Rating Scale score and abolition of dyskinesia in 40% of cases. For BPVP, these figures were increased to 31% and 63%, respectively. Follow‐up of a smaller group to 12 months found the motor scores to be worsening but benefit to dyskinesia and activities of daily living was maintained. Speech was adversely affected after BPVP, although the change was small in most cases. Unilateral and bilateral pallidotomy can be performed safely without microelectrode localisation. Bilateral pallidotomy appears to be more effective, particularly in reducing dyskinesia; in our experience, the side effects have not been as high as reported by other groups.

Cerebrovascular biomodelling: a technical note

BACKGROUND Recently computed tomographic angiography (CTA) and MR angiography (MRA) have been used to image cerebrovascular structures. Although CTA and MRA are accurate and sensitive imaging modalities, limitations have been identified in relation to image interpretation. Stereolithographic (SL) biomodelling is a new technology that allows three-dimensional (3D) CT and MR data to be used to accurately manufacture solid plastic replicas of anatomical structures. A prospective trial of SL biomodelling in cerebrovascular surgery has been performed to investigate the feasibility and clinical utility of this new display medium. METHODS Fifteen patients with cerebral aneurysms and 1 patient with a cerebral arteriovenous malformation (AVM) were selected. 3D CT and/or MR angiograms were acquired and 19 solid anatomical biomodels manufactured using the rapid prototyping technology of stereolithography. The biomodels were used for patient education, diagnosis, operative planning and surgical navigation. RESULTS The biomodels replicated the CTA and MRA source data. The accuracy of one biomodel was verified by comparison with a post mortem specimen, which corresponded exactly in the x and y planes but differed by 2 mm in the z plane. The ability to closely study an overview of complex cerebrovascular anatomy from any perspective on a solid biomodel was reported to enhance the surgeons understanding, particularly when conventional images were equivocal. Cerebrovascular biomodels were found to be useful when positioning the patients head for surgery, for selecting the best aneurysm clip and for the simulation of clipping. Patient informed consent was anecdotally improved. Disadvantages of the technology were the cost and manufacturing time. CONCLUSIONS Cerebrovascular biomodelling may have utility in complex cases or when the standard imaging is felt to be equivocal.

Defining a role for the subthalamic nucleus within operative theoretical models of subcortical participation in language

Objective:To investigate the effects of bilateral, surgically induced functional inhibition of the subthalamic nucleus (STN) on general language, high level linguistic abilities, and semantic processing skills in a group of patients with Parkinson’s disease. Methods:Comprehensive linguistic profiles were obtained up to one month before and three months after bilateral implantation of electrodes in the STN during active deep brain stimulation (DBS) in five subjects with Parkinson’s disease (mean age, 63.2 years). Equivalent linguistic profiles were generated over a three month period for a non-surgical control cohort of 16 subjects with Parkinson’s disease (NSPD) (mean age, 64.4 years). Education and disease duration were similar in the two groups. Initial assessment and three month follow up performance profiles were compared within subjects by paired t tests. Reliability change indices (RCI), representing clinically significant alterations in performance over time, were calculated for each of the assessment scores achieved by the five STN-DBS cases and the 16 NSPD controls, relative to performance variability within a group of 16 non-neurologically impaired adults (mean age, 61.9 years). Proportions of reliable change were then compared between the STN-DBS and NSPD groups. Results:Paired comparisons within the STN-DBS group showed prolonged postoperative semantic processing reaction times for a range of word types coded for meanings and meaning relatedness. Case by case analyses of reliable change across language assessments and groups revealed differences in proportions of change over time within the STN-DBS and NSPD groups in the domains of high level linguistics and semantic processing. Specifically, when compared with the NSPD group, the STN-DBS group showed a proportionally significant (p<0.05) reliable improvement in postoperative scores achieved on the word test-revised (TWT-R), as well as a reliable decline (p<0.01) in the accuracy of lexical decisions about words with many meanings and a high degree of relatedness between meanings. Conclusions:Bilateral STN-DBS affects certain aspects of linguistic functioning, supporting a potential role for the STN in the mediation of language processes.

Redefining functional models of basal ganglia organization: Role for the posteroventral pallidum in linguistic processing

Traditionally the basal ganglia have been implicated in motor behavior, as they are involved in both the execution of automatic actions and the modification of ongoing actions in novel contexts. Corresponding to cognition, the role of the basal ganglia has not been defined as explicitly. Relative to linguistic processes, contemporary theories of subcortical participation in language have endorsed a role for the globus pallidus internus (GPi) in the control of lexical–semantic operations. However, attempts to empirically validate these postulates have been largely limited to neuropsychological investigations of verbal fluency abilities subsequent to pallidotomy. We evaluated the impact of bilateral posteroventral pallidotomy (BPVP) on language function across a range of general and high‐level linguistic abilities, and validated/extended working theories of pallidal participation in language. Comprehensive linguistic profiles were compiled up to 1 month before and 3 months after BPVP in 6 subjects with Parkinsons disease (PD). Commensurate linguistic profiles were also gathered over a 3‐month period for a nonsurgical control cohort of 16 subjects with PD and a group of 16 non‐neurologically impaired controls (NC). Nonparametric between‐groups comparisons were conducted and reliable change indices calculated, relative to baseline/3‐month follow‐up difference scores. Group‐wise statistical comparisons between the three groups failed to reveal significant postoperative changes in language performance. Case‐by‐case data analysis relative to clinically consequential change indices revealed reliable alterations in performance across several language variables as a consequence of BPVP. These findings lend support to models of subcortical participation in language, which promote a role for the GPi in lexical–semantic manipulation mechanisms. Concomitant improvements and decrements in postoperative performance were interpreted within the context of additive and subtractive postlesional effects. Relative to parkinsonian cohorts, clinically reliable versus statistically significant changes on a case by case basis may provide the most accurate method of characterizing the way in which pathophysiologically divergent basal ganglia linguistic circuits respond to BPVP.

Biomodelling of skull base tumours

Stereolithographic (SL) biomodelling is a new technology that allows three-dimensional computed tomography magnetic resuance data to be used to generate solid plastic replicas of anatomical structures (biomodels). A prospective trial of 11 patients to assess the utility of SL biomodelling in skull base tumour surgery has been performed. Biomodels were manufactured and used for patient education, diagnosis and operative planning. The results suggest that biomodelling has significant utility in skull base tumour surgery and is a cost-effective technology. Biomodels were found to be particularly effective for surgical simulation and the production of customised cranioplastic implants for reconstruction after tumour resection. Copyright 1999 Harcourt Publishers Ltd.

Beyond verbal fluency: Investigating the long-term effects of bilateral subthalamic (STN) deep brain stimulation (DBS) on language function in two cases

Cognitive functioning has been described as largely impervious to chronic STN-DBS administered over 12-month periods. In relation to the domain of language, however, the effects of STN-DBS are yet to be thoroughly delineated. Verbal fluency tasks represent an almost exclusively applied index of linguistic proficiency relative to neuropsychological research within this population. Comprehensive investigations of the impact of STN-DBS on language function, however, have never been undertaken. The more precise elucidation of the role of the STN in the mediation of language processes, by way of assessments which probe language comprehension and production mechanisms, served as the primary focus of this research. Longitudinal analysis also afforded consideration of the way in which cognitive-linguistic circuits respond to STN-DBS over time. Bilateral STN-DBS primarily effected clinically reliable fluctuations (i.e., both improvements and declines) in performance in both subjects on tasks demanding cognitive-linguistic flexibility in the formulation and comprehension of complex language. Of particular note, both subjects demonstrated a cumulative increase in the proportion of reliable post-operative improvements achieved over time. The findings of this research lend support to models of subcortical participation in language which endorse a role for the STN, and suggest that bilateral STN-DBS may serve to enhance the proficiency of basal ganglia-thalamocortical linguistic circuits over time.

Reappraising contemporary theories of subcortical participation in language: Proposing an interhemispheric regulatory function for the subthalamic nucleus (STN) in the mediation of high-level linguistic processes

Abstract Apropos the basal ganglia, the dominant striatum and globus pallidus internus (GPi) have been hypothesized to represent integral components of subcortical language circuitry. Working subcortical language theories, however, have failed thus far to consider a role for the STN in the mediation of linguistic processes, a structure recently defined as the driving force of basal ganglia output. The aim of this research was to investigate the impact of surgically induced functional inhibition of the STN upon linguistic abilities, within the context of established models of basal ganglia participation in language. Two males with surgically induced ‘lesions’ of the dominant and non-dominant dorsolateral STN, aimed at relieving Parkinsonian motor symptoms, served as experimental subjects. General and high-level language profiles were compiled for each subject up to 1 month prior to and 3 months following neurosurgery, within the drug-on state (i.e., when optimally medicated). Comparable post-operative alterations in linguistic performance were observed subsequent to surgically induced functional inhibition of the left and right STN. More specifically, higher proportions of reliable decline as opposed to improvement in post-operative performance were demonstrated by both subjects on complex language tasks, hypothesised to entail the interplay of cognitive-linguistic processes. The outcomes of the current research challenge unilateralised models of functional basal ganglia organisation with the proposal of a potential interhemispheric regulatory function for the STN in the mediation of high-level linguistic processes.

Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors

Here we report the identification of a proliferative, viable, and hyperdiploid tumor cell subpopulation present within Glioblastoma (GB) patient tumors. Using xenograft tumor models, we demonstrate that hyperdiploid cell populations are maintained in xenograft tumors and that clonally expanded hyperdiploid cells support tumor formation and progression in vivo. In some patient tumorsphere lines, hyperdiploidy is maintained during long-term culture and in vivo within xenograft tumor models, suggesting that hyperdiploidy can be a stable cell state. In other patient lines hyperdiploid cells display genetic drift in vitro and in vivo, suggesting that in these patients hyperdiploidy is a transient cell state that generates novel phenotypes, potentially facilitating rapid tumor evolution. We show that the hyperdiploid cells are resistant to conventional therapy, in part due to infrequent cell division due to a delay in the G₀/G₁ phase of the cell cycle. Hyperdiploid tumor cells are significantly larger and more metabolically active than euploid cancer cells, and this correlates to an increased sensitivity to the effects of glycolysis inhibition. Together these data identify GB hyperdiploid tumor cells as a potentially important subpopulation of cells that are well positioned to contribute to tumor evolution and disease recurrence in adult brain cancer patients, and suggest tumor metabolism as a promising point of therapeutic intervention against this subpopulation.

Routine multidisciplinary cerebrovascular meetings do not reduce aneurysm clipping case load: a cohort study.

Structured multidisciplinary care is an increasingly popular tool in the management of many complex disease processes; however, there is little published data regarding the effects of such a process on management of intracranial aneurysms and neurosurgical case loads. There is some resistance in the neurosurgical community to routine involvement of interventional neuroradiologists in the care of patients with intracranial aneurysms due to concerns regarding maintenance of neurosurgical case loads and training capabilities. At our tertiary Australian hospital, we have implemented a weekly multidisciplinary cerebrovascular meeting (MDCVM) facilitating routine discussion of these cases between neurosurgeons and interventional neuroradiologists.