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Summary Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. Methods: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. Results: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and “most severe” seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. Discussion: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.

This chapter explores the history of 3D printing and associated emerging technological applications. 3D printing is the most tangible physical output of modern computer technology and as such has the power to impact beyond the core IT technologies into both personalized and mainstream manufacturing. If used correctly, these technologies can reduce the carbon footprint of manufacturing and change the manufacturing paradigm (Factory 2.0), resulting in a highly distributed model of production. The origins of 3D printing are described, and the range of underlying technologies are explained. 3D printing technologies are advancing in two domains: the domestic hobbyist level and the high-value manufacturing level. Despite there being significant price differences (of printing technology) within these two domains, entrepreneur start-up communities have generated a range of innovations from Web-based technologies, open-source designs, recycling methods, innovative organic materials, and new hybrid approaches to printing. The chapter identifies the emergence of new hybrid technologies that impact both ends of the market and have advantages relating to environmental issues in reduction of materials usage, energy usage, and transportation cost. A theme of organic sustainable materials and recycling of materials for remanufacture is also explored and offers pathways to new innovative low-carbon products.

This contribution discusses the aetiology of learning disability. Learning disability, termed ‘mental retardation’ in ICD-10, is defined as significantly below average general intellectual functioning (IQ

Objectives: To evaluate the one year cognitive, mood state, and quality of life (QoL) outcomes of unilateral thalamic deep brain stimulation (DBS) for essential tremor (ET). Methods: 40 patients diagnosed with ET completed comprehensive neuropsychological assessments about one month before and three and 12 months after DBS electrode implantation. Data were subjected to multivariate analyses, and significant results were further analysed using univariate techniques. Results: Analyses revealed statistically significant improvements on a cognitive screening measure and in aspects of fine visuomotor and visuoperceptual functions, verbal memory, mood state, and QoL. No group-wise declines in cognition were observed, but more patients showed declines than improvements on language and visual memory tests. Semantic verbal fluency declined significantly in four (10%) of the patients. In these four patients, diminished lexical verbal fluency was present at baseline. Conclusion: Cognitive, mood, and QoL outcomes after one year of DBS for ET are favourable; there were no overall deleterious effects on cognition, and DBS was accompanied by a significant reduction in anxiety and improvements in quality of life. However, preoperative verbal fluency diminution may predispose to further fluency declines after DBS.

The long-term neuropsychological and quality of life (QOL) outcomes of unilateral thalamic deep brain stimulation (DBS) in patients with intractable Parkinson's disease (PD) have not heretofore been described. Six patients diagnosed with PD underwent unilateral DBS implantation into a verified thalamic VIM nucleus target. Participants completed presurgical neuropsychological evaluation and follow-up assessment at approximately one year postsurgery. Compared to their presurgical scores, PD patients exhibited significant improvement on measures of conceptualization, verbal memory, emotional adjustment, and QOL at one-year follow-up. A few nominal declines were observed across the battery of tests. These data provide preliminary support for the long-term neurocognitive safety and QOL improvements following thalamic stimulation in patients with PD.

The relative accuracy of starting point algorithms in microelectrode-guided stereotactic pallidotomy and thalamotomy was evaluated using postoperative magnetic resonance imaging (MRI) data. Multiplanar reformations were performed to align postoperative MRI in anterior-posterior, dorsal-ventral and mediolateral planes. Three-dimensional distance and direction from the pallidal and thalamic stereotactic starting points to the respective radiofrequency lesions were measured. Similar magnitude of microelectrode refinement in pallidotomy and thalamotomy suggested similar accuracy of algorithms used to set the stereotactic starting point. Fewer microelectrode-recording tracts were required to identify optimal lesioning sites in thalamotomy compared to pallidotomy. Lesions were consistently localized anterior and superior to the starting point and a refined starting point algorithm may reduce the number of microelectrode recording tracts.

In 1997, Homeswest in western Australia and Murdoch University developed a project to construct low-allergen houses (LAHs) in a newly developed suburb. Before the construction of LAHs, all potential volatile organic compound (VOC) emission materials used in LAHs are required to be measured to ensure that they are low total VOC (TVOC) emission materials. This program was developed based on this purpose. In recent times, the number of complaints about indoor air pollution caused by VOCs has increased. A number of surveys of indoor VOCs have indicated that many indoor materials contribute to indoor air pollution. Although some studies have been conducted on the characteristics of VOC emissions from adhesives, most of them were focused on VOC emissions from floor adhesives. Few measurements of VOC emissions from adhesives used for wood, fabrics, and leather are available. Furthermore, most research on VOC emissions from adhesives has been done in countries with cool climates, where ventilation rates in the indoor environment are lower than those in Mediterranean climates, due to energy conservation. VOCs emitted from adhesives have not been sufficiently researched to prepare an emission inventory to predict indoor air quality and to determine both exposure levels for the Australian population and the most appropriate strategies to reduce exposure. An environmental test chamber with controlled temperature, relative humidity, and airflow rate was used to evaluate emissions of TVOCs from three adhesives used frequently in Australia. The quantity of TVOC emissions was measured by a gas chromatography/flame ionization detector. The primary VOCs emitted from each adhesive were detected by gas chromatography/mass spectrometry. The temporal change of TVOC concentrations emitted from each adhesive was tested. A double-exponential equation was then developed to evaluate the characteristics of TVOC emissions from these three adhesives. With this double-exponential model, the physical processes of TVOC emissions can be explained, and a variety of emission parameters can be calculated. These emission parameters could be used to estimate real indoor TVOC concentrations in Mediterranean climates.

OBJECTIVE: To determine whether stereotactic pallidotomy requires refinement using microelectrode recording to ensure proper lesion placement. METHODS: The experiment approach was based on retrospective comparisons of microelectrode-refined radiofrequency lesion locations with hypothetical unrefined lesion positions. Actual and hypothetical pallidotomy lesions were classified based on their lesion center (thermocoagulative zone) locations and their total lesion areas (surrounding edematous zone) relative to the pallidal target. Assessments were made using postoperative T2-weighted magnetic resonance axial images, which showed both the lesion and globus pallidus (GP). The magnitude of microelectrode refinement from an initial preoperative starting point determined by computed tomography was calculated using stereotactic coordinates and included corrections for the lesioning tract trajectory angle. RESULTS: In all 25 patients, the center of the actual pallidotomy lesion was within the GP. Without microelectrode refinement, 13 of 25 hypothetical lesion positions would have been localized such that the lesion center would not have remained in the GP. In eight cases, microelectrode refinement resulted in no significant change in lesion location, but in one case, microelectrode refinement resulted in lesion center placement away from the GP. CONCLUSION: Kinesthetically driven microelectrode refinement in pallidotomy lesioning seems to be required to ensure proper lesion location within the GP.

Surgical treatment of Parkinson's disease has become an important mode of therapy for advanced disease. Both ablative lesions and, more recently, deep brain stimulation have been employed. Various brain areas, including the thalamus, globus pallidus, and subthalamus, have been target sites.

Accuracy of pallidotomy lesion placement was assessed by comparing actual lesion locations with expected pallidotomy lesion locations based on stereotaxy. Actual and expected lesions were compared in anteroposterior, dorsoventral and lateral axes. In 22 pallidotomies, actual lesion locations were determined using axial MR images. Expected lesion locations were calculated using a starting point derived from preoperative computerized tomography, displacements from the starting point based on microelectrode-driven electrophysiological refinement, and the trajectory angle of the lesioning tract relative to the anterior-posterior commissural plane. On average, actual lesion locations were found 2.91 ± 2.23 mm posterior, 3.22 ± 2.49 mm ventral, and 0.05 ± 1.80 mm lateral compared to the expected lesion location. Discrepancies between the actual lesion and expected lesion locations may be mostly accounted for by posterior and ventral lesion spread from the exposed electrode tip, in-plane and volume averaging effects associated with MR images, and possible brain shifting during surgery. However, despite the remaining small differences between actual and expected lesion location, good clinical outcome of reduced dyskinesias and ‘off’ time along with UPDRS-based improvement in mentation, motor and activity of daily living measures was observed.

Acute thalamotomy and pallidotomy lesion volumes based on magnetic resonance (MR) images were measured in 22 patients (11 thalamotomy and 11 pallidotomy patients). Thalamotomy inner lesion volumes (0.06 ± 0.04 ml; thermocoagulative zone) were smaller than pallidotomy inner lesion volumes (0.14 ± 0.08 ml) as determined using T1-weighted 3D-MPRAGE (1.5-mm slice spacing). Similar results were found using T1-weighted (6-mm slice spacing) image sets (0.09 ± 0.05 ml, thalamotomy; 0.13 ± 0.05 ml, pallidotomy). No differences were found when comparing thalamic or pallidal inner lesion volumes when the comparison was based on T2 weighted images. Thalamotomy total lesion volumes (thermocoagulative and surrounding edematous zones) were less than pallidotomy total lesion volumes independent of the MR protocol. The difference in thalamotomy and pallidotomy lesion volumes is most likely based on the distance between each discrete lesion placed along the lesioning tracts. In 7 of 11 thalamotomies, this distance was 1 mm with the remaining having 2 mm between each discrete lesion. All pallidotomy discrete lesions were 2 mm apart. More overlap between discrete lesioning sites for thalamotomies is likely to produce reduced lesion volumes.

OBJECTIVE: To assess the position of radiofrequency pallidotomy lesions placed using microelectrode stimulation and cellular recordings in relation to a stereotactically defined starting point. Radiofrequency lesion locations were also evaluated in relation to the putamen, posterior limb of the internal capsule, and optic tract. METHODS: Magnetic resonance images obtained from 23 patients with Parkinson's disease who underwent pallidotomy at the University of Kansas Medical Center were analyzed. Using computerized techniques, lesion positions in relation to the midcommissural point and a hypothetical starting point were determined. Data segmentation and three-dimensional reconstruction of pallidal lesions, the internal capsule, and the optic tract allowed assessment of lesion position in relation to internal anatomy. Clinical outcome of pallidotomy was assessed using both the Unified Parkinson's Disease Rating Scale and the Dementia Rating Scale. RESULTS: Pallidal lesions were usually placed anterior and dorsal to the stereotactically defined starting point. The position of pallidal lesions in the men were observed, in four trials, to be significantly more dorsal than the lesions in the women. The outer zone of the lesion was usually adjacent to the internal capsule and the putamen and relatively close to the optic tract. The inner zone of the lesion was usually several millimeters removed from anatomic boundaries of the putamen, internal capsule, and optic tract. Patients achieved favorable outcomes, with reduced dyskinesias and off time and improvement of their Parkinsonian symptoms, as evidenced by clinical assessment, the Unified Parkinson's Disease Rating Scale, and the Dementia Rating Scale. CONCLUSION: Microelectrode stimulation and cellular recordings usually led to a final pallidotomy lesion position that deviated from the stereotactically defined starting point. The pallidotomy lesions in the men were observed to be more dorsal than the lesions in the women. Clinical outcomes were not correlated with either lesion location relative to the starting point or distances between the pallidal lesion and the putamen, internal capsule, or optic tract. Kinesthetically responsive cells may be localized generally more anterior and dorsal to the starting point (within the globus pallidus) and may be grouped variably from patient to patient in relation to other basal ganglia structures. Although the primary lesion site is most likely within the sensorimotor region of the globus pallidus internus, the more dorsal locations of responsive cell groups may indicate that some lesion sites may be localized within the globus pallidus externus.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

It has been suggested that deep brain stimulation (DBS) is less effective in alleviating proximal than distal postural arm tremor reduction is said to be less in essential tremor (ET) than in Parkinson's disease (PD). We analyzed blinded rater's tremor scores and subjects' disability ratings at 3-month follow-up to examine the effects of DBS based on tremor type (rest, kinetic, distal postural, proximal postural) and diagnosis (ET, PD). An independent examiner provided tremor scores using randomized videotaped footage of 19 ET and 10 PD subjects at baseline and at follow-up with DBS "on." Subjects provided self-ratings of disability at baseline and at follow-up. Comparisons of baseline and follow-up tremor scores and disability ratings were made using the Mann-Whitney U and Wilcoxon rank sum W test; correlation analyses were performed using Spearman rank order correlation test. There were significant and essentially equal improvements in tremor scores of test, kinetic, distal postural, and proximal postural tremor at follow-up. Only one subject had no improvement in tremor. Tremor improved significantly and to the same extent in ET and PD subjects in each position except "at rest," which was most improved in PD (p = 0.0003). ET and PD subjects did not differ in the extent of disability improvement. Improved disability correlated only with improved postural tremor scores; proximal postural and distal postural (r = 0.41, p = 0.03; r = 0.47, p = 0.01). DBS is effective in alleviating tremor and disability in both ET and PD. Resting, kinetic, distal postural, and proximal postural tremor can be reduced to an equal degree. However, DBS produces the greatest improvement in disability in association with improved postural tremor in both ET and PD.

The objective was to investigate the long term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in Parkinson's disease. Twelve patients with Parkinson's disease underwent unilateral DBS of the thalamus for medication resistant tremor between 1994 and 1997. Patients were evaluated with the motor section of the unified Parkinson's disease rating scale (UPDRS) in the medication on state at baseline, 3 months, 12 months, and yearly thereafter. Three patients were lost to follow up. Nine patients had follow up evaluations greater than 24 months and were included in the analyses. The last postsurgical follow up occurred on average 40.0 (SD 17.2) months after surgery. Tremor scores were significantly improved with stimulation on at the long term follow up compared with baseline. There was no significant change in UPDRS motor scores at long term follow up compared with baseline. There was no significant change in any stimulus parameters from 3 months to the long term follow up. Two patients had asymptomatic intracerebral haemorrhages and one patient had a subcutaneous haematoma over the implantable pulse generator site. Stimulus related adverse reactions were mild and easily controlled with changes in stimulus parameters. Two patients had replacement of the implantable pulse generator due to normal battery depletion, one patient had lead repositioning due to migration, and one patient had the lead extension wire replaced due to erosion. In conclusion, unilateral DBS of the thalamus has long term efficacy for treatment of tremor due to Parkinson's disease.

Augmented and Mixed Reality technology provides to the medical field the possibility for seamless visualization of text-based physiological data and various graphical 3D data onto the patient's body. This allows improvements in diagnosis and treatment of patients. For the patient, this technology offers benefits and further potential in therapy, rehabilitation and diagnosis, and explanation. Applications across the whole range of functions that affect the health sector from the physician, the medical student, to the patients are possible. However, the quality of the work of medical professionals is considerably influenced by both usefulness and usability of technology. Consequently, key issues in developing such applications are the tracking methodology, the display technology and most of all ensuring good usability. There have been several research groups who extended the state of the art in employing these technologies in the medical domain. However, only a few are addressing issues of Human-Computer Interaction, Interaction Design, and Usability Engineering. This paper provides a brief overview over the history and the most recent developments in this domain with a special focus on issues of user-centered development.

Individuals with Down's syndrome are predisposed to a variety of medical conditions which can impose an additional, but preventable, burden of secondary disability. Although there are guidelines for health checks and medical management of children with Down's syndrome, the needs of adults are relatively neglected.To determine the prevalence of common medical problems in adults with Down's syndrome, and to assess current practice regarding medical surveillance of these patients.Detailed notes analysis.Data were obtained from the primary care records of adults with Down's syndrome living in the Newcastle upon Tyne and Gateshead areas.Case notes were reviewed to obtain details regarding complications and to determine the frequency of medical surveillance of individuals with Down's syndrome.Complications such as hypothyroidism, celiac disease, and obesity occur more frequently in adults with Down's syndrome than previous paediatric prevalence studies suggest. Surveillance of common complications that occur in individuals with Down's syndrome is infrequent. In this study, 48% of adults with Down's syndrome had not seen a doctor in the previous 12 months and 33% had not had a medical assessment in the previous 3 years.Many individuals with Down's syndrome do not have access to regular healthcare checks, despite the high frequency of common medical complications in adult life. Debate regarding the practicality and relevance of introducing regular health checks is warranted.

The number of online resources for biodiversity information is growing. Names of organisms underpin access to information but present a number of unique problems when used as search terms. We examine these problems and assert that a taxonomic name-server or thesaurus is necessary to enable optimal retrieval of records from multiple datasets. A simple solution is presented, based upon our experience working with "real-world" data in the National Biodiversity Network (NBN) in the United Kingdom. The NBN provides access to over 18 million observational records and incorporates a nomenclator covering 198,000 names.

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.

Background Modern persistent organic pollutants (POPs) contamination are logical candidates in the investigation of the, as yet, unexplained association between allergic disease and progressive industrialisation. POPs have been detected in human cord blood, placental tissues and breast milk, and the reported association between cord blood IgE levels and cord/placental POP levels has raised concerns about potential immunological effects in early life. Methods The initial aim of this study was to determine if POPs were detectable in maternal blood, cord blood, placental tissues, adipose tissue and breast milk samples from randomly selected Western Australian women ( n = 31), where allergic disease is epidemic. Gas chromatography was used to detect polychlorinated biphenyl compounds [PCBs] (as Aroclor 1232, 1254, 1260) and organochlorine (OC) pesticides, including p , p ′-DDT, p , p ′-DDE, hexachlorobenzene (HCB), lindane, heptachlor epoxide, dieldrin and chlordane. Secondly, we assessed the relationship between POP levels detected in vivo and maternal and neonatal responses (cytokine and lymphoproliferation) to allergens and mitogens. Results Low level POP contamination was detected in adipose tissue and breast milk (but not in cord blood, maternal blood or placental tissues). The most ubiquitous compound found in over 90% of adipose tissues samples was a OC metabolite of DDT, p , p ′-DDE (median 0.07 mg/kg; interquartile range [IQR] 0.05–0.12). However, the majority of other OC compounds were not detectable and PCB were not detectable in any samples. The three main residues detected in breast milk were p , p ′-DDE (0.003 mg/l; 0.001–0.009), dieldrin (0.001 mg/l; 0.001–0.046) and HCB (0.001 mg/l; 0.001–0.001). These levels are significantly lower than reported over 20 years ago. There were no consistent relationships between POP levels in vivo and maternal or infant responses, with the exception of a significant inverse association (Spearman rank correlation: r = −0.406, p = 0.049) between maternal adipose tissue levels of OC p , p ′-DDE and maternal T helper cell Type 1 interferon [IFN] γ to mitogens. Conclusion This study provides the first evidence (in Australia) since the early 1990’s that adipose OC levels have continued to fall. The negligible levels in this randomly selected group are significantly lower than those previously recorded, suggesting that POP contamination (at biologically relevant levels) is not likely to be a major contributing factor in the increasing rates of allergy in Western Australia. However, the relationship between Th1 immune function and OC contamination is consistent with other reports and is worth investigating as a relevant factor in populations where OC contamination is greater.

Since the furnace section of a boiler is the primary heat transfer surface for the production of vapor, the overall water circulation patterns in the boiler will be significantly influenced by the circulation patterns near the furnace area. Boiler water circulation characteristics for a newly designed 4-pass firetube boiler with the non-symmetric arrangement of tube passes 3 and 4 were investigated in the previous work [1], in which the attraction forces between 28 different temperature nodes on the furnace wall were evaluated to predict the characteristics of water circulation near the boiler furnace. It was found that various non-symmetric water circulation patterns would occur for different firing conditions. As a consequence, in this paper, the analysis methods developed in the authors’ previous work are explicitly employed to predict and improve the water circulation in a firetube boiler when 6 different boiler feedwater inlet locations (3 on the right-hand side and 3 on the left-hand side of the boiler vessel shell) are used. Each side has 3 different feedwater inlet locations below the centerline of the boiler pressure vessel along its length. Investigation of the analysis results reveals that non-symmetric water circulation patterns are not unavoidable, but improvements in the water circulation and potentially the heat transfer rate can be achieved when the boiler feed water inlet is located near the front head of the boiler pressure vessel.Copyright © 2002 by ASME

Water circulation characteristics, for a newly designed 4-pass 300 BHP (Boiler Horse Power) firetube boiler with a non-symmetric arrangement of tube passes 3 and 4, are investigated in this paper by means of measured furnace wall temperatures for different boiler firing conditions. Vapor production rate and intensity, at each of the 28 temperature measurement nodes, is approximated using the nodal temperature in conjunction with a nucleate boiling heat transfer mode on the water side of the furnace. Defining an attraction force that is proportional to the relative difference of the evaporation intensity between two nodes and inversely proportional to the distance between, the two-dimensional components of the attraction force can be calculated. Integrating all attraction force vectors between a node and the surrounding nodes produces a representative attraction force vector at the node. Similar calculation of the attraction force vectors at all of the temperature nodes on the furnace wall will characterize the water circulation near the boiler furnace. Investigations of the analysis results reveal various complicated non-symmetric water circulation patterns for different boiler firing conditions. Consequently, the analysis methods employed in this paper can be used to predict and improve the water circulation in a firetube boiler, particularly with regard to the placement of the boiler feed-water inlet location.

SUMMARY The increased procedural demands of stereotactic localization techniques when compared with conventional treatment practices reduces machine efficiency, an outcome likely to be greatly magnified by the introduction of fractionation to stereotactic techniques. Currently in Australia and New Zealand there are no guidelines for the definition of efficiency. We sought to devise a system to simultaneously validate the accuracy and efficiency of the technique. The frameless relocation methods employed in the Medtronic Sofamor Danek (MSD) stereotactic radiotherapy (SRT) system were studied in the clinical setting. Accuracy has been determined according to the accumulation of errors throughout the planning and treatment process. The clinical demands of the system (staffing and resources) were analysed relative to conventional treatment approaches. Timing studies indicate a mean time of 19.7 min for treatment of a daily SRT fraction (4–5 arcs, single isocentre). Cost and staffing requirements are similar to those for conventional radiotherapy. It is concluded that with the system used, SRT is efficient for routine clinical implementation, with the level of efficiency increasing with increasing patient numbers. It is recommended that a common acceptance standard be developed to allow cross-institutional comparison of the clinical efficiency of new treatment techniques.

OBJECTIVE: Microelectrode recording can refine targeting for stereotactic radiofrequency lesioning of the globus pallidus to treat Parkinson's disease. Multiple intraoperative microelectrode recording/stimulating tracks are searched and assessed for neuronal activity, presence of tremor cells, visual responses, and responses to kinesthetic input. These physiological data are then correlated with atlas-based anatomic data to approximate electrode location. On the basis of these physiological properties, one or more tracks are selected for lesioning. This study analyzes the track physiological factors that seem most significant in determining the microelectrode recording track(s) that will be chosen for pallidal lesioning. METHODS: Thirty-six patients with Parkinson's disease underwent microelectrode-guided pallidotomy. Between one and five microelectrode recording tracks were made per patient. Usually, one (n = 23) or two (n = 12) of these tracks were lesioned. Electrode positions in the x (mediolateral) and y (anteroposterior) axes were recorded and related to track neurophysiological findings and final lesion location. The stereotactic location and sequence of microelectrode tracks were recorded and plotted to illustrate individual search patterns. These patterns were then compared with those noted in other patients. Neurophysiological data obtained from recording tracks were analyzed. A retrospective analysis of track electrophysiology was performed to determine the track characteristics that seemed most important in the surgeon's choice of the track to lesion. Track physiological properties included general cell spike amplitude, tremor synchronous neuronal firing, kinesthetically responsive neuronal firing, and optic track responses (either phosphenes reported by the patient during track microstimulation or neuronal firing in response to light stimulus into the patient's eyes). Orthogonally corrected postoperative magnetic resonance images were used to confirm the anatomic lesion locations. RESULTS: In patients who had a single mapped track lesioned, specific track electrophysiological characteristics identified the track that would be lesioned most of the time (20 of 24 patients). Tracks that exhibited a combination of tremor synchronous firing, joint kinesthesia, and visual responsivity were lesioned 17 (85%) of 20 times. Analysis of intraoperative electrode movement in the x and y axes indicated a significant subset of moves but did not result in microelectrode positioning closer to the subsequently lesioned track. Accuracy of initial electrode movement in the x and y axes was most highly correlated with a measure of first-track electrophysiological activity. The number of microelectrode recording tracks did not correlate with clinical outcome. Anatomic analysis, using postoperative magnetic resonance imaging, revealed that all lesions were placed in the globus pallidus. Most patients (35 of 36) improved after surgery. CONCLUSION: The level of electrophysiological activity in the first track was the best predictive factor in determining whether the next microelectrode move would be closer to the ultimately lesioned track. The analysis of electrode track location and neurophysiological properties yields useful information regarding the effectiveness of microelectrode searching in the x and y axes. Within an institution, the application of this modeling method may increase the efficiency of the microelectrode refinement process.

Objective: To evaluate short-term effects of unilateral thalamic deep brain stimulation (DBS) on cognition, mood state, and quality of life in patients with essential tremor (ET). Background: Unilateral thalamotomy and thalamic DBS are effective in alleviating refractory tremor contralateral to the side of surgery. Thalamotomy can lead to cognitive morbidity, and DBS might be a preferable surgical intervention given potential avoidance or reversibility of such morbidity. Although unilateral thalamic DBS is cognitively safe and leads to quality of life improvement in PD, its neurobehavioral effects in ET are unknown. Methods: Forty patients with ET were administered a broad neuropsychological test battery, measures of mood state, and generic and disease-specific quality of life measures approximately 1 month before and 3 months after surgery (left hemisphere, 38 patients). Results: Unilateral thalamic DBS was associated with significant improvements in tremor and dominant-hand fine visuomotor coordination. Statistically significant but clinically modest gains were observed on tasks of visuoperceptual and constructional ability, visual attention, delayed word list recognition, and prose recall. Only lexical verbal fluency declined significantly after surgery. Patients rated themselves as less anxious after surgery, and they perceived their quality of life as improved significantly. In particular, patients reported improved quality of life with respect to activities of daily living, stigma, emotional well-being, and communication. Conclusions: Unilateral thalamic DBS for ET is cognitively safe and associated with improvements in anxiety and quality of life in the near term and in the absence of operative complications. Patients were better able to carry out activities of daily living after surgery, and they reported improvement in several psychosocial domains of quality of life.

Postoperative lesion volume and clinical outcome were assessed in 19 Parkinson’s disease (PD) patients who received posteroventral pallidotomy, and in 14 essential tremor (ET) patients who received ventrolateral thalamotomy. Before and after surgery, PD patients were evaluated using the Unified PD Rating Scale (UPDRS), and ET patients were evaluated using the Fahn-Tolosa-Marin (FTM) tremor rating scale. Inner and total lesion volumes were determined with postoperative MR imaging and three-dimensional data segmentation. Lesion volumes were compared to percent improvement in UPDRS and FTM scores, using Spearman’s rank-order correlation test. No rank-order correlations were found between lesion volume and clinical improvement in either the PD or the ET patients. In performing stereotactic surgery for movement disorders, any lesion volume within a prescribed range may be equally effective in relieving symptoms associated with PD or ET.

Deep brain stimulation (DBS) of the thalamus reduces tremor in patients with essential tremor (ET). However, few studies have determined the degree of improvement in daily functioning associated with DBS. We developed a self-report Tremor Activities of Daily Living Scale (TADLS) to compare daily functioning with the stimulator turned on and off. Patients rated their performance on the 30 items of the TADLS with the stimulator turned off and then on. They also performed 10 activities under the supervision of a clinician who rated their functional ability with stimulation off and then on. There was a 58% improvement in self-rated TADLS scores in patients with DBS with the stimulator on compared with stimulation off. When activities were rated by the clinician, the average improvement in functioning with the stimulator on was 54%. There were reasonably high correlations between patient and clinician ratings of functioning. ET patients have a marked improvement in daily functioning with thalamic DBS.

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus(CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p< 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.

Thymic carcinoid is part of the multiple endocrine neoplasia type 1 (MEN1) syndrome occurring predominantly in male patients who were heavy smokers, presenting most commonly in middle age. In contrast with metastatic midgut carcinoids, MEN1-related thymic carcinoid is not associated with carcinoid syndrome, nor is it associated with Cushing syndrome, in contrast with sporadic thymic carcinoids. Local invasion and metastasis are common. Prognosis is poor because of late detection, lack of effective treatment, and the aggressive nature of the tumor. All patients with thymic carcinoids should be investigated for MEN1, including thorough clinical evaluation and family studies. Anterior mediastinal lesions in MEN1 male patients should be considered thymic carcinoids until proven otherwise. All male MEN1 patients and asymptomatic gene carriers should be warned of the risk of thymic carcinoids and the possible link to smoking. Computed tomography (CT) of the chest is recommended on first screening for MEN1 in male patients more than 25 years of age, followed by yearly chest X-rays and chest CT every 3 years. Prophylactic thymectomy should be carried out during subtotal or total parathyroidectomy on MEN1 patients.

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.

Determination of acute pallidotomy-produced lesion volumes, pre- and postpallidotomy globus pallidus (GP) volumes, and assessment of lesion shape using magnetic resonance (MR) imaging-based computerized segmentation (contouring) and three-dimensional rendering was made in 19 patients. Magnetic resonance image slice thickness (1.5 mm or 6 mm) was not found to be a significant factor influencing contour-based pallidotomy lesion volume estimates. Previously reported lesion volumes produced by pallidotomy have often been estimated using the ellipsoid volume formula. Using 1.5-mm-thick MR sections, contour-based pallidotomy-produced lesion volumes were significantly different from those volumes estimated by the ellipsoid formula. Globus pallidus volumes, estimated by contouring T2-weighted MR images, were bilaterally similar (2.4 ± 0.37 ml [right]; 2.2 ± 0.45 ml [left]). Postoperative GP volumes were found on the contralateral, unlesioned side to be 2 ± 0.45 ml and on the lesioned side to be 1.25 ± 0.45 ml. Using the contralateral, unlesioned side as a reference volume, approximately 39 ± 14% of the GP was visibly affected on the lesioned side. Seventeen of 18 patients had a favorable outcome with reduced dyskinesias and "off" time with improvement in parkinsonian symptoms. Analysis of computerized three-dimensional rendering of pallidotomy-produced lesions based on MR images showed no relationship between lesioning technique and resulting lesion shape. Important factors in the volumetric analysis of pallidotomy lesions are identified and allow reasonable assessment of the pallidotomy lesion volume and shape and the extent of the affected GP.