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Objective: To investigate the effects of extraoperative electrical stimulation of fiber tracts connecting the language territories. Methods: We describe results of extraoperative electrical stimulation of stereotactic electrodes in 3 patients with epilepsy who underwent presurgical evaluation for epilepsy surgery. Contacts of these electrodes sampled, among other structures, the suprainsular white matter of the left hemisphere. Results: Aside from speech disturbance and speech arrest, subcortical electrical stimulation of white matter tracts directly superior to the insula representing the anterior part of the arcuate fascicle, reproducibly induced complex verbal auditory phenomena including (1) hearing one9s own voice in the absence of overt speech, and (2) lack of perception of arrest or alteration in ongoing repetition of words. Conclusion: These results represent direct evidence that the anterior part of the arcuate fascicle is part of a network that is important in the mediation of speech planning and awareness likely by linking the language areas of the inferior parietal and posterior inferior frontal cortices. More specifically, our observations suggest that this structure may be relevant to the pathophysiology of thought disorders and auditory verbal hallucinations.

Purpose To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). Methods and Materials Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. Results The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. Conclusions This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

Object The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT). Methods In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3). Results Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdalae on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another. Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure—namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations and a relatively fixed peak-to-peak interval before MHT. This fixed interpeak delay disappeared after the first transection, although high cross-correlation values persisted unchanged. All patients who underwent MHT remained seizure free for more than 2 years. Conclusions These data suggest that synchronized discharges involving the complete anterior-posterior axis of the hippocampal/parahippocampal (H/P) formation underlie the spread of epileptiform discharges outside the H/P structures and, therefore, for the generation of epileptic seizures originating in the H/P structures. This conclusion is supported by the following observations. 1) Hippocampal spikes are consistently synchronized in the whole hippocampal structures, with a fixed delay between the different hippocampal areas. 2) One or two transections between the head and body of the hippocampal formation are sufficient to abolish hippocampal spikes that are synchronized along the anterior-posterior axis of the hippocampus. 3) Treatment with MHT leads to seizure freedom in patients with H/P epilepsy.

The insula is the fifth lobe of the brain and it is the least known. Hidden under the temporal, frontal and parietal opercula, as well as under dense arterial and venous vessels, its accessibility is particularly restricted. Functional data on this region in humans, therefore, are scarce and the existing evidence makes conclusions on its functional and somatotopic organization difficult. 5 patients with intractable epilepsy underwent an invasive presurgical evaluation with implantation of diagnostic invasive-depth electrodes, including insular electrodes that were inserted using a mesiocaudodorsal to laterorostroventral approach. Altogether 113 contacts were found to be in the insula and were stimulated with alternating currents during preoperative monitoring. Different viscerosensitive and somatosensory phenomena were elicited by stimulation of these electrodes. A relatively high density of electrode contacts enabled us to delineate several functionally distinct areas within the insula. We found somatosensory symptoms to be restricted to the posterior insula and a subgroup of warmth or painful sensations in the dorsal posterior insula. Viscerosensory symptoms were elicited by more anterior electrode contacts with a subgroup of gustatory symptoms occurring after stimulation of electrode contacts in the central part of the insula. The anterior insula did not show reproducible responses to stimulation. In line with previous studies, we found evidence for somato- and viscerosensory cortex in the insula. In addition, our results suggest that there is a predominantly posterior and central distribution of these functions in the insular lobe. Electronic supplementary material The online version of this article (doi:10.1007/s00429-010-0296-3) contains supplementary material, which is available to authorized users.

A recent pilot crossover study of deep brain stimulation for Tourette syndrome involved the counting of motor and sonic tics from video recordings of patients. The evaluation of a five-minute video (divided into ten 30-second segments) in each of eight intervention states per patient was found to be very tedious and time-consuming. The present study sought to determine the statistical implications of reducing this data collection burden. To make maximal use of data from the small sample (n=5) pilot study, we fit linear mixed effects models to the tic count data. As suggested by an empirical examination of within-person correlations, a novel random effects covariance structure, which we refer to as a 'partitioned random effects model' was found to provide the best fit to the data. The best model for each tic type was then used to estimate relative efficiencies for specified data reductions. This analysis indicated that using a subset of five out of 10 segments would require only a 10% increase in sample size to maintain a specified power. Lastly, the bias of estimated treatment effects based on the reduced data collection was evaluated, and the particular five-segment subsets with the smallest estimated bias were determined.

Object: Although benign and slow growing, glomus jugulare tumors can be locally aggressive because of their proximity to lower cranial nerves and major vascular structures. Surgical resection frequently leads to complications, and radiosurgery alone often does not relieve symptoms. We report a novel treatment paradigm of tailored surgical resection followed by staged radiosurgery that allows for tissue diagnosis and immediate improvement of symptoms and tumor control without the morbidity of radical surgical resection. Methods: Five patients with glomus jugulare tumors and contraindications to extensive surgery each underwent an outpatient otologic procedure to resect the portion of the tumor in the middle ear and mastoid with no attempt to remove tumor in the jugular bulb. Each patient returned 2–5 months later for Gamma Knife radiosurgery to the remainder of the tumor, which consisted of one 15-Gy dose prescribed to the 50% isodose curve. Patients were followed through outpatient visits and surveillance MR imaging for up to 3 years. Results: All patients were successfully treated as outpatients. Each had improvement or resolution of pulsatile tinnitus and otalgia and preserved or improved hearing. One patient developed a delayed facial palsy prior to radiosurgery that resolved completely; there were no other changes in cranial nerve function after either procedure. Tumor volume was stable or reduced in all patients at most recent follow-up, and there were no immediate or delayed complications. Conclusions: Staged outpatient microsurgical and radiosurgical therapy for glomus jugulare tumors in the symptomatic patient is safe and yields favorable results regarding tumor size, tinnitus, hearing and cranial nerve status.

Object The severity of Tourette syndrome (TS) typically peaks just before adolescence and diminishes afterward. In some patients, however, TS progresses into adulthood, and proves to be medically refractory. The authors conducted a prospective double-blind crossover trial of bilateral thalamic deep brain stimulation (DBS) in five adults with TS. Methods Bilateral thalamic electrodes were implanted. An independent programmer established optimal stimulator settings in a single session. Subjective and objective results were assessed in a double-blind randomized manner for 4 weeks, with each week spent in one of four states of unilateral or bilateral stimulation. Results were similarly assessed 3 months after unblinded bilateral stimulator activation while repeated open programming sessions were permitted. Results In the randomized phase of the trial, a statistically significant (p < 0.03, Friedman exact test) reduction in the modified Rush Video-Based Rating Scale score (primary outcome measure) was identified in the bilateral on state. Improvement was noted in motor and sonic tic counts as well as on the Yale Global Tic Severity Scale and TS Symptom List scores (secondary outcome measures). Benefit was persistent after 3 months of open stimulator programming. Quality of life indices were also improved. Three of five patients had marked improvement according to all primary and secondary outcome measures. Conclusions Bilateral thalamic DBS appears to reduce tic frequency and severity in some patients with TS who have exhausted other available means of treatment.

The objective of our study was to evaluate intraoperative low-field MRI for the frequency and duration of imaging sessions needed during surgery, the direct additional procedure time attributable to imaging, and the proportion of cases in which information provided by intraoperative MRI led to a change in the procedure or otherwise was deemed valuable by operating surgeons.One hundred twenty-two patients (65 males, 57 females; age range, 6-77 years; mean age, 43.8 years) underwent 130 neurosurgical and ENT procedures (106 craniotomies, 17 transsphenoidal pituitary resections, three biopsies, three intracranial cyst aspirations or injections, and one skull base resection) in a specially designed surgical MRI suite equipped with a 0.2-T imager and a prototype rotating, tiltable surgical table. The intraoperative MR sequences included free induction with steady-state precession (fast imaging with steady-state precession [FISP]), steady-state free precession T2-weighted, reverse fast imaging with steady-state free precession (PSIF), FLASH, spin-echo T1-weighted, turbo spin-echo (TSE) T2-weighted, and TSE FLAIR. Each case was analyzed for the number of imaging sessions, duration of each session, total imaging time during surgery, and impact of imaging information on procedure.Each patient underwent between one and five intraor postoperative imaging sessions. Imaging times were 1.7 seconds-8 minutes 31 seconds per sequence. The mean total imaging time was 35 minutes 17 seconds per surgical procedure. Imaging was continuous during biopsy and cyst aspiration procedures and averaged 200.67 and 54.66 minutes, respectively. Additional surgical resection based on intraoperative imaging findings was performed in 72.8% of the cases.Intraoperative low-field MRI provides valuable information for surgical decision making that is predominantly related to detection of residual tumor and the exclusion of complications. The benefits of this technology surpass the time cost associated with its implementation when using proper imaging strategies.

This study proposes and simulates an inverse treatment planning and a continuous dose delivery approach for the Leksell Gamma Knife registered (LGK, Elekta, Stockholm, Sweden) which we refer to as 'Tomosurgery'. Tomosurgery uses an isocenter that moves within the irradiation field to continuously deliver the prescribed radiation dose in a raster-scanning format, slice by slice, within an intracranial lesion. Our Tomosurgery automated (inverse) treatment planning algorithm utilizes a two-stage optimization strategy. The first stage reduces the current three-dimensional (3D) treatment planning problem to a series of more easily solved 2D treatment planning subproblems. In the second stage, those 2D treatment plans are assembled to obtain a final 3D treatment plan for the entire lesion. We created Tomosurgery treatment plans for 11 patients who had already received manually-generated LGK treatment plans to treat brain tumors. For the seven cases without critical structures (CS), the Tomosurgery treatment plans showed borderline to significant improvement in within-tumor dose standard deviation (STD) (p =}20% or {>=}30% of the maximum dose) showed no significant improvement in the Tomosurgery treatment plans (p

In radiosurgery, conformity indices are often used to compare competing plans, evaluate treatment techniques, and assess clinical complications. Several different indices have been reported to measure the conformity of the prescription isodose to the target volume. The PITV recommended in the Radiation Therapy Oncology Group (RTOG) radiosurgery guidelines, defined as the ratio of the prescription isodose volume (PI) over the target volume (TV), is probably the most frequently quoted. However, these currently used conformity indices depend on target size and shape complexity. The objectives of this study are to systematically investigate the influence of target size and shape complexity on existing conformity indices, and to propose a different conformity index–the conformity distance index (CDI). The CDI is defined as the average distance between the target and the prescription isodose line. This study examines five case groups with volumes of 0.3, 1.0, 3.0, 10.0, and 30.0 cm3. Each case group includes four simulated shapes: a sphere, a moderate ellipsoid, an extreme ellipsoid, and a concave “C” shape. Prescription dose coverages are generated for three simplified clinical scenarios, i.e., the PI completely covers the TV with 1 and 2 mm margins, and the PI over‐covers one half of the TV with a 1 mm margin and under‐covers the other half with a 1 mm margin. Existing conformity indices and the CDI are calculated for these five case groups as well as seven clinical cases. When these values are compared, the RTOG PITV conformity index and other similar conformity measures have much higher values than the CDI for smaller and more complex shapes. With the same quality of prescription dose coverage, the CDI yields a consistent conformity measure. For the seven clinical cases, we also find that the same PITV values can be associated with very different conformity qualities while the CDI predicts the conformity quality accurately. In summary, the proposed CDI provides more consistent and accurate conformity measurements for all target sizes and shapes studied, and therefore will be a more useful conformity index for irregularly shaped targets. PACS number(s): 87.90.+y, 87.53.Ly

OBJECTIVE Despite the growing popularity of frameless image-guided surgery systems, stereotactic frame systems are widely accepted by neurosurgeons and are commonly used to perform biopsies, functional procedures, and stereotactic radiosurgery. We investigated the accuracy of the Brown-Roberts-Wells stereotactic frame system when the mechanical load on the frame changes between preoperative imaging and the intervention because of different patient position: supine during imaging, prone during intervention. METHODS We analyzed computed tomographic images acquired from 14 patients who underwent stereotactic biopsy, deep brain stimulator implantation, or radiosurgery. Two images were acquired for each patient, one with the patient in the supine position and one in the prone position. The prone images were registered to the respective supine images by use of an intensity-based registration algorithm, once using only the frame and once using only the head. The difference between the transformations produced by these two registrations describes the movement of the patient's head with respect to the frame. RESULTS The maximum frame-based registration error between the supine and prone positions was 2.8 mm; it was more than 2 mm in two patients and more than 1.5 mm in six patients. Anteroposterior translation is the dominant component of the difference transformation for most patients. In general, the magnitude of the movement increased with brain volume, which is an index of head weight. CONCLUSION To minimize frame-based registration error caused by a change in the mechanical load on the frame, stereotactic procedures should be performed with the patient in the identical position during imaging and intervention.

Purpose: To develop a novel dose optimization algorithm for improving the sparing of critical structures during gamma knife radiosurgery by shaping the plug pattern of each individual shot. Method and Materials: We first use a geometric information (medial axis) aided guided evolutionary simulated annealing (GESA) optimization algorithm to determine the number of shots and isocenter location, size, and weight of each shot. Then we create a plug quality score system that checks the dose contribution to the volume of interest by each plug in the treatment plan. A positive score implies that the corresponding source could be open to improve tumor coverage, whereas a negative score means the source could be blocked for the purpose of sparing normal and critical structures. The plug pattern is then optimized via the GESA algorithm that is integrated with this score system. Weight and position of each shot are also tuned in this procedure. Results: An acoustic tumor case is used to evaluate our algorithm. Compared to the treatment plan generated without plug patterns, adding an optimized plug pattern into the treatment planning process boosts tumor coverage index from 95.1% to 97.2%, reduces RTOG conformity index from 1.279 to 1.167, lowers Paddick's index from 1.34 to 1.20, and trims the critical structure receiving more than 30% maximum dose from 16 mm 3 to 6 mm 3 . Conclusions: Automated GESA-based plug pattern optimization of gamma knife radiosurgery frees the treatment planning team from the manual forward planning procedure and provides an optimal treatment plan.

Background: Intraoperative magnetic resonance (MR) imaging has been employed as an alternative to image guidance using preoperative images. We integrated both systems to evaluate their clinical use. Methods: The BrainLAB VectorVisionTM system was integrated in an intraoperative Siemens Open Viva 0.2-tesla MR system. Clinical experience was assessed. Results: Patterns of intraoperative imaging emerged, and benefit was seen in registering preoperative and intraoperative images. Conclusions: This integrated system has clinically observed effects on imaging, navigation, and surgery.

Objective Tourette syndrome (TS) is a neuropsychiatric disorder presenting with motor and/or sonic tics associated with frontostriatal dysfunction. This study provided pilot data of the neuropsychological safety of bilateral thalamic deep brain stimulation (DBS) to treat medication-refractory TS in adults. Method This study used a repeated-measures design with pretest and 3-month follow-up from start of continuous bilateral DBS. Five male patients underwent DBS surgery for medically refractory TS. Repeated-measures ANOVA was used to evaluate for any change in neuropsychological test scores, employing a false discovery rate. Outcome measures included 14 neuropsychological tests assessing psychomotor speed, attention, memory, language, visuoconstructional, and executive functions, as well as subjective mood ratings of depression and anxiety. Results Average age was 28.2 years (SD = 7.5) with 12–17 years of education. Participants were disabled by tics, with a tic frequency of 50–80 per minute before surgery. At baseline, subjects' cognitive function was generally average, although mild deficits in sequencing and verbal fluency were present, as were clinically mild obsessive–compulsive symptoms. At 3 months of continuous DBS (5 months after implantation), 3 of 5 participants had clinical reductions in motor and sonic tics. Cognitive scores generally remained stable, but declines of moderate to large effect size (Cohen's d > 0.6) in verbal fluency, visual immediate memory, and reaction time were observed. Fewer symptoms of depression and anxiety, as well as fewer obsessions and compulsions, were reported after 3 months of continuous high-frequency DBS. Conclusions Bilateral centromedian–parafascicular thalamic DBS for medically refractory TS shows promise for treatment of medically refractory TS without marked neuropsychological morbidity. Symptoms of depression and anxiety improved.

OBJECTIVE: To demonstrate that the shape of the configuration of fiducial points is an important factor governing target registration error (TRE) in point-based, rigid registration. METHODS: We consider two clinical situations: cranial neurosurgery and pedicle screw placement. For cranial neurosurgery, we apply theoretical results concerning TRE prediction, which we have previously derived and validated, to three hypothetical fiducial marker configurations. We illustrate the profile of expected TRE for each configuration. For pedicle screw placement, we apply the same theory to a common anatomic landmark configuration (tips of spinous and transverse processes) used for pedicle screw placement, and we estimate the error rate expected in placement of the screw. RESULTS: In the cranial neurosurgery example, we demonstrate that relatively small values of TRE may be achieved by using widely spread fiducial markers and/or placing the centroid of the markers near the target. We also demonstrate that near-collinear marker configurations far from the target may result in large TRE values. In the pedicle screw placement example, we demonstrate that the screw must be approximately 4 mm narrower than the pedicle in which it is implanted to minimize the chance of pedicle violation during placement. CONCLUSION: The placement of fiducial points is an important factor in minimizing the error rate for point-based, rigid registration. By using as many points as possible, avoiding near-collinear configurations, and ensuring that the centroid of the fiducial points is as near as possible to the target, TREs can be minimized. (Neurosurgery 48:810‐817, 2001)

The primary objective of this study is to perform a blinded evaluation of two groups of retrospective image registration techniques, using as a gold standard a prospective marker-based registration method, and to compare the performance of one group with the other. These techniques have already been evaluated individually [27]. In this paper, however, we find that by grouping the techniques as volume based or surface based, we can make some interesting conclusions which were not visible in the earlier study. In order to ensure blindness, all retrospective registrations were performed by participants who had no knowledge of the gold-standard results until after their results had been submitted. Image volumes of three modalities: X-ray computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) were obtained from patients undergoing neurosurgery at Vanderbilt University Medical Center on whom bone-implanted fiducial markers were mounted. These volumes had all traces of the markers removed and were provided via the Internet to project collaborators outside Vanderbilt, who then performed retrospective registrations on the volumes, calculating transformations from CT to MR and/or from PET to MR. These investigators communicated their transformations, again via the Internet, to Vanderbilt, where the accuracy of each registration was evaluated. In this evaluation, the accuracy is measured at multiple volumes of interest (VOI's). Our results indicate that the volume-based techniques in this study tended to give substantially more accurate and reliable results than the surface-based ones for the CT-to-MR registration tasks, and slightly more accurate results for the PET-to-MR tasks. Analysis of these results revealed that the rotational component of error was more pronounced for the surface-based group. It was also apparent that all of the registration techniques we examined have the potential to produce satisfactory results much of the time, but that visual inspection is necessary to guard against large errors.

Advances in imaging resolution have resulted in superior visualization of intracranial anatomy. Because of the inherent complexity of the surgical exposure of these lesions, intraoperative localizing techniques are required. Currently, C-arm fluoroscopy provides only two-dimensional localization for these anatomic structures. The recently described ACUSTAR I system, developed in conjunction with Codman and Shurtleff, Inc. (Randolph, Mass.), is an interactive, image-guided device that allows three-dimensional localization with a degree of accuracy previously unattainable. We assessed the clinical utility of the ACUSTAR I system for intraoperative spatial confirmation during transsphenoidal approaches to pituitary lesions.Eight patients underwent transsphenoidal approaches to pituitary lesions with the assistance of the ACUSTAR I system. The spatial relationships were clinically judged intraoperatively by the surgeon and by use of traditional C-arm fluoroscopy and then were compared with the ACUSTAR I system results.In all eight patients, the ACUSTAR I system correctly displayed the surgical orientation and provided localization to within less than 1 mm. In two patients, this facilitated the redirection of an errant approach. No complications were associated with the use of this image-guided device.The ACUSTAR I system is useful in displaying accurate, three-dimensional anatomic relationships during transsphenoidal approaches to pituitary lesions. This system provides critical information intraoperatively to redirect errant approaches and prevent significant morbidity.

Most previously reported registration techniques that align three-dimensional image volumes by matching geometrical features such as points or surfaces use a single type of feature. The authors recently reported a hybrid registration technique that uses a weighted combination of multiple geometrical feature shapes. In this study they use the weighted geometrical feature (WGF) algorithm to register computed tomography (CT) images of the head to physical space using the skin surface only, the bone surface only, and various weighted combinations of these surfaces and one fiducial point (centroid of a bone-implanted marker). The authors use data acquired from 12 patients that underwent temporal lobe craniotomies for the resection of cerebral lesions. The authors evaluate and compare the accuracy of the registrations obtained using these various approaches by using as a reference gold standard the registration obtained using three bone-implanted markers. The results demonstrate that a combination of geometrical features can improve the accuracy of CT-to-physical space registration. Point-based registration requires a minimum of three noncollinear points. The position of a bone-implanted marker can be determined much more accurately than that of a skin-affixed marker or an anatomic landmark. A major disadvantage of using bone-implanted markers is that an invasive procedure is required to implant each marker. By combining surface information, the WGF algorithm allows registration to be performed using only one or two such markers. One important finding is that the use of a single, very accurate point (a bone-implanted marker) allows very accurate surface-based registration to be achieved using very few surface points. Finally, the WGF algorithm, which not only allows the combination of multiple types of geometrical information but also handles point-based and surface-based registration as degenerate cases, could form the foundation of a "flexible" surgical navigation system that allows the surgeon to use what he considers the method most appropriate for an individual clinical situation.

Among early-passage, near-diploid gliomas in vitro, transforming growth factor type β (TGFβ) has been previously shown to be an autocrine growth inhibitor. In contrast, hyperdiploid (≥ 57chromosomes/metaphase) glioblastoma multiforme (HD-GM) cultures were autocrinely stimulated by the TGFβ. The mechanism of this ‘conversion’ from autocrine inhibitor to mitogen is not understood; previous studies have suggested that platelet-derived growth factor (PDGF) might be modulated by TGFβ. The similar expression of TGFβ types 1—3, PDGF-AA, — BB, as well as the PDGF receptor α and β subunits (a/βPDGFR) between biopsies of the HD-GM and near-diploid, TGFβ-inhibited glioblastomas (GM) by immunohistochemistry did not explain the discrepancy in their regulatory responses. Flowcytometry demonstrated that TGFβ's mitogenic effect was selective for the aneuploid subpopulations of two of three selected HD-GM cultures,while the diploid cells were inhibited. Among the HD-GM, TGFβ1 induced the RNA of PDGF-A, c-sis and TGFβ1. The amount of PDGF-AA secreted following TGFβ treatment was sufficient to stimulate the proliferation of a HD-GM culture. Antibodies against PDGF-AA, -BB, -AB,αPDGFR and/or βPDGFR subunits effectively neutralized TGFβ's induction of DNA synthesis among the HD-GM cell lines, indicating that PDGF served as the principal mediator of TGFβ's growth stimulatory effect. By comparison, TGFβ induced only the RNA of PDGF-A and TGFβ1 among the near-diploid GM; c-sis was not expressed at all. However, the amount of PDGF-A which was secreted in response to TGFβ1 was insufficient to prevent TGFβ's arrest of the near-diploid cultures in G1 phase. Thus, the emergence of hyperdiploidy was associated with qualitative and quantitative differences in TGFβ's modulation of PDGF-A and c-sis, which provided a mechanism by which the aneuploid glioma cellsmight achieve ‘clonal dominance’. We hypothesize that TGFβ may serve as an autocrine promoter of GM progression by providing a selective advantage to the hyperdiploid subpopulation through the loss of a tumor suppressor gene which mediates TGFβ's inhibitory effect.

In this article we investigate the effect of geometrical distortion correction in MR images on the accuracy of the registration of X-ray CT and MR head images for both a fiducial marker (extrinsic point) method and a surface-matching technique. We use CT and T2-weighted MR image volumes acquired from seven patients who underwent craniotomies in a stereotactic neurosurgical clinical trial. Each patient had four external markers attached to transcutaneous posts screwed into the outer table of the skull. The MR images are corrected for static field inhomogeneity by using an image rectification technique and corrected for scale distortion (gradient magnitude uncertainty) by using an attached stereotactic frame as an object of known shape and size. We define target registration error (TRE) as the distance between corresponding marker positions after registration and transformation. The accuracy of the fiducial marker method is determined by using each combination of three markers to estimate the transformation and the remaining marker to calculate registration error. Surface-based registration is accomplished by fitting MR contours corresponding to the CSF-dura interface to CT contours derived from the inner surface of the skull. The mean point-based TRE using three noncollinear fiducials improved 34%-from 1.15 to 0.76 mm-after correcting for both static field inhomogeneity and scale distortion. The mean surface-based TRE improved 46%-from 2.20 to 1.19 mm. Correction of geometrical distortion in MR images can significantly improve the accuracy of point-based and surface-based registration of CT and MR head images. Distortion correction can be important in clinical situations such as stereotactic and functional neurosurgery where 1 to 2 mm accuracy is required.

An image processing technique is presented for finding and localizing the centroids of cylindrical markers externally attached to the human head in computed tomography (CT) and magnetic resonance (MR) image volumes. The centroids can be used as control points for image registration. The technique, which is fast, automatic, and knowledge-based, has two major steps. First, it searches the entire image volume to find one voxel inside each marker-like object. The authors call this voxel a "candidate" voxel, and they call the object a candidate marker. Second, it classifies the voxels in a region surrounding the candidate voxel as marker or nonmarker voxels using knowledge-based rules and calculates an intensity-weighted centroid for each true marker. The authors call this final centroid the "fiducial" point of the marker. The technique was developed on 42 scans of six patients-one CT and six MR scans per patient. There are four markers attached to each patient for a total of 168 marker images. For the CT images the false marker rate was zero. For MR the false marker rate was 1.4% (Two out of 144 markers). To evaluate the accuracy of the fiducial points, CT-MR registration was performed after correcting the MR images for geometrical distortion. The fiducial registration accuracy averaged 0.4 mm and was better than 0.6 mm for each of the eighteen image pairs.

Interactive image-guided neurosurgical techniques allow safer and more complete cy tor eduction of gliomas. This is most significant for low-grade tumors, whose configurations and margins are perhaps better appreciated by reference to registered MR images rather than by reliance on direct visualization using microscopic illumination. Spatially registered electro-physiologic recordings of intraoperative cortical stimulation to map language and motor function can increase the margin of safety for performing radical resections. By individualizing approaches and optimizing results, these technologies promise a new degree of standardization of outcome after resective surgery for all glial tumors.

The authors present a weighted geometrical feature (WGF) registration algorithm. Its efficacy is demonstrated by combining points and a surface. The technique is an extension of Besl and McKay's (1992) iterative closest point (ICP) algorithm. The authors use the WGF algorithm to register X-ray computed tomography (CT) and T2-weighted magnetic resonance (MR) volume head images acquired from eleven patients that underwent craniotomies in a neurosurgical clinical trial. Each patient had five external markers attached to transcutaneous posts screwed into the outer table of the skull. The authors define registration error as the distance between positions of corresponding markers that are not used for registration. The CT and MR images are registered using fiducial paints (marker positions) only, a surface only, and various weighted combinations of points and a surface. The CT surface is derived from contours corresponding to the inner surface of the skull. The MR surface is derived from contours corresponding to the cerebrospinal fluid (CSF)-dura interface. Registration using points and a surface is found to be significantly more accurate then registration using only points or a surface.

Accurate stereotactic navigation depends strongly upon the spatial fidelity of the image used for registration. Clinically significant levels of geometric distortion are present in standard MR images, limiting their utility. A technique for correction of all geometric distortions in spine echo MR images was assessed in a prospective clinical trial of 19 stereotactic craniotomies. The Euclidean error in target registration between CT and MR was significantly reduced, from 3.833 +/- 0.992 to 1.986 +/- 0.605 mm. The results of this clinical trial support the incorporation of this MR image rectification protocol into standard clinical practice.

Objective: To describe the morbidity associated with seizures and the efficacy of anticonvulsant therapy in adult patients with malignant gliomas (MGs). Study Design: A retrospective review of charts was performed to determine the occurrence of seizures at diagnosis, the frequency and character of subsequent seizures, and the use and toxic side effects of anticonvulsants. Patients: Sixty-five consecutive adult patients with supratentorial MGs who were examined in the neurooncology clinic at a university medical center were studied. The diagnosis was glioblastoma in 47 of the patients, and it was anaplastic astrocytoma in 18 patients. The mean age of the patients was 49.5 years. The median Karnofsky status score was 80. The median survival was 18 months. Results: Twenty-nine patients presented with seizures, and 21 21 of these had subsequent (eg, "recurrent") seizures while they were receiving anticonvulsant therapy. Ten of 36 patients who were free of seizures at diagnosis experienced seizures after diagnosis (eg, "late onset") while they were being treated with anticonvulsants, including five patients who had single seizures. Long-term seizure frequency in excess of one per month was observed in 13 patients. Ten patients had episodes of partial motor status epilepticus. Most recurrent and late-onset seizures occurred despite therapeutic anticonvulsant levels, and without evidence of tumor progression. Rash associated with anticonvulsants was observed in 26% of the patients. Other clinically important toxic side effects were observed in 14% of the patients who were receiving long-term anticonvulsant therapy. Conclusions: Seizures contributed substantially to the neurologic morbidity of MGs in at least 25% of these patients. The occurrence of seizures at diagnosis was a strong predictor of subsequent seizures, and in many patients, seizures proved to be refractory to standard anticonvulsant therapy. Long-term anticonvulsant toxic side effects are relatively common in patients with MGs. The use of long-term seizure prophylaxis for patients with MGs who are free of seizures at presentation is not clearly beneficial and should be studied in a prospective trial.

Precise localization of subcortical targets contributes to the technical challenge of craniotomies. To address this challenge, the application of readily available stereotactic localization techniques to open craniotomies was investigated. Over a 2-year period, 62 consecutive stereotactic craniotomies were performed successfully using the CT-compatible Brown-Roberts-Wells (BRW) apparatus. Standard BRW hardware and software were employed. This series consists of craniotomies in 50 patients for resection of subcortical mass lesions. Targets were consistently and precisely localized by the stereotactic frame. Pathology revealed 32 metastases, 18 glial tumors, 5 nonglial tumors, and 7 nonneoplastic lesions. Histology differed from presumptive diagnoses by neurodiagnostic imaging studies in 30.6% of cases. The average volume of tumors resected was 55,903 mm3. Gross total resection of all solid tumor tissue was consistently confirmed by postoperative contrast-enhanced CT. Postoperatively, 38 patients with masse...

The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT).In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3).Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdala on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another. Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure--namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations and a relatively fixed peak-to-peak interval before MHT. This fixed interpeak delay disappeared after the first transection, although high cross-correlation values persisted unchanged. All patients who underwent MHT remained seizure free for more than 2 years.These data suggest that synchronized discharges involving the complete anterior-posterior axis of the hippocampal/parahippocampal (H/P) formation underlie the spread of epileptiform discharges outside the H/P structures and, therefore, for the generation of epileptic seizures originating in the H/P structures. This conclusion is supported by the following observations. 1) Hippocampal spikes are consistently synchronized in the whole hippocampal structures, with a fixed delay between the different hippocampal areas. 2) One or two transections between the head and body of the hippocampal formation are sufficient to abolish hippocampal spikes that are synchronized along the anterior-posterior axis of the hippocampus. 3) Treatment with MHT leads to seizure freedom in patients with H/P epilepsy.

Previous investigators have supported the idea that glucocorticoids may be oncolytic. In this study, the percentage of cell death in two human glioblastoma cell cultures was related to the concentration of dexamethasone that was administered. It was determined that for Cell line 1, the median lethal dose was approximately 500-800 micrograms/ml and the completely lethal dose was about 900-1000 micrograms/ml; the 3H-thymidine uptake to approximate the mitotic rate was 16,607 cpm, and the dexamethasone receptor activity was 228 fmol/mg protein. The median lethal dose and completely lethal dose for Cell line 2 was approximately 500-600 micrograms/ml and 700-1000 micrograms/ml, respectively; the 3H-thymidine uptake was 8402 cpm, and the dexamethasone receptor activity was 137 fmol/mg protein. These lethal concentrations of dexamethasone are probably higher than can be tolerated by systemic delivery. However, it remains to be seen whether the interstitial administration of dexamethasone could achieve local concentrations resulting in the oncolysis of malignant gliomas. The clinical significance of these findings will depend on the local tolerance of normal brain parenchyma to very high doses of dexamethasone. A review of some of the literature is included.

Recently, interest has grown in the area of low-power laser effects upon tissues. We used a 51Cr cell labeling technique with glioma tissue to better understand these effects. Canine 2C5 gliosarcoma cells with intracellular 51Cr were exposed to CO2 laser in the range of 0.2 to 3.0 J/cm2. Correlative analysis of the data indicated that there is a strong direct relationship between laser fluence and the percent of total intracellular 51Cr released from the glioma cells with a coefficient of correlation (r) of +0.93. The calculated standard error of the correlation coefficient was ± 0.06 and the coefficient of determination (r2) was 0.86. These results indicate that the 51Cr cell labeling technique is a useful method for quantifying the low-power laser effects on the integrity of the cell membrane of gliosarcoma cells in vitro. However, further investigation is needed to clarify the specific mechanisms by which the CO2 laser induces changes upon these cells. © 1993 Wiley-Liss, Inc. © 1993 Wiley-Liss, Inc.

This chapter reviews the anatomy, physiology, treatment and cognitive/neuropsychological aspects of movement disorders, of which Parkinson’s disease (PD) and parkinsonism are common manifestations. The neurologic, cognitive and behavioral aspects of movement disorders are covered in detail as are contemporary treatments and treatment outcomes. This chapter starts with an overview of the functional neuroanatomy of movement and discusses normal motor movement and disordered motor movement. We review the role of the basal ganglia and other anatomical areas implicated in movement disorders including Parkinson’s disease and parkinsonism and the role of dopamine and other neurotransmitters in disorders of movement. The next section reviews the clinical presentation of the movement disorders, inclusive of a description of each ­disorders cardinal symptoms and the differentiating characteristics among movement disorders. The cognitive and emotional symptoms associated with movement disorders are also discussed in detail. The later part of this chapter discusses the available treatment for movement disorders such as pharmacotherapy and surgical options and the motor and cognitive outcomes from such treatments. Next, the chapter provides a detailed analysis for the pre-surgical evaluation of patients being considered for surgical treatment, including a review of the pre- and post-operative neuropsychological assessment of patients with movement disorders. We discuss the changes in neuropsychological function that may be predicted post-surgically. Finally, we propose directions for future research in the course and treatment outcomes in motor, cognitive and behavioral symptoms associated with movement disorders.

Coexistence of cortical dysplasias (CD) with cavernomas has rarely been reported. We reviewed our surgical specimens from patients who underwent surgery for pharmacoresistant epilepsy between 2003 and 2008, and identified seven cases with cavernoma, of whom two had overlying CD. In addition, each of these patients had a third form of a potentially epileptogenic lesion: hippocampal sclerosis in one, and venous angioma in the other. We conclude that CD is heterogeneous, with milder forms appearing to co-exist with other pathologies, including vascular abnormalities and hippocampal sclerosis.

Glomus jugulare tumors arise from adventitial chemoreceptor tissue in the jugular bulb. Although histologically benign, these tumors can be locally aggressive because of their proximity to the lower cranial nerves and major vascular structures. Traditional treatment involves microsurgical removal with or without endovascular embolization, but morbidity following total resection can result in injury to the facial and lower cranial nerves. Radiosurgery has recently emerged as a promising alternative to older therapeutic strategies for treatment of glomus jugulare tumors. This article reviews the latest benefits of radiosurgery and demonstrates how this modality represents an effective treatment option for glomus jugulare tumors with excellent tumor control and low risk for morbidity. In addition, this article will detail the role of minimally invasive sub-total resection of glomus jugulare tumors as a surgical complement to gamma knife therapy.