A case of developmental pedophilia unmasked by frontotemporal dementia.

A 65-year-old right-handed man gradually became socially indifferent and less active. Four years later, he was indicted for molesting children on multiple occasions. Psychomotor slowness and executive impairment contrasted with sparing of language, semantic memory, visuospatial perception, construction praxis, and right-left orientation. Neuroimaging showed asymmetric atrophy of dorsomedial frontal and anterior temporal lobes, and hypoperfusion of medial prefrontal cortex consistent with a diagnosis of behavioral variant of frontotemporal dementia. Further information revealed that the patient exhibited pedophilic behavior several years prior to symptom onset. We conclude that preexisting developmental pedophilia was "unmasked" by the underlying progressive frontotemporal degeneration.

Stereotactic Radiosurgery for Benign (World Health Organization Grade I) Cavernous Sinus Meningiomas-International Stereotactic Radiosurgery Society (ISRS) Practice Guideline: A Systematic Review.

BACKGROUND: Stereotactic radiosurgery (SRS) has become popular as a standard treatment for cavernous sinus (CS) meningiomas. OBJECTIVE: To summarize the published literature specific to the treatment of CS meningioma with SRS found through a systematic review, and to create recommendations on behalf of the International Stereotactic Radiosurgery Society. METHODS: Articles published from January 1963 to December 2014 were systemically reviewed. Three electronic databases, PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials, were searched. Publications in English with at least 10 patients (each arm) were included. RESULTS: Of 569 screened abstracts, a total of 49 full-text articles were included in the analysis. All studies were retrospective. Most of the reports had favorable outcomes with 5-yr progression-free survival (PFS) rates ranging from 86% to 99%, and 10-yr PFS rates ranging from 69% to 97%. The post-SRS neurological preservation rate ranged from 80% to 100%. Resection can be considered for the treatment of larger (>3 cm in diameter) and symptomatic CS meningioma in patients both receptive to and medically eligible for open surgery. Adjuvant or salvage SRS for residual or recurrent tumor can be utilized depending on factors such as tumor volume and proximity to adjacent critical organs at risk. CONCLUSION: The literature is limited to level III evidence with respect to outcomes of SRS in patients with CS meningioma. Based on the observed results, SRS offers a favorable benefit to risk profile for patients with CS meningioma.

Radiosurgery for Secondary Trigeminal Neuralgia: Revisiting the Treatment Paradigm.

BACKGROUND: The mechanisms by which surgery and radiation elicit pain relief in trigeminal neuralgia (TN) secondary to mass lesions vary widely. We aimed to evaluate the outcomes of radiation to the nerve rather than to the lesion in the treatment of secondary TN. METHODS: We retrospectively reviewed all patients who underwent radiation at the University of California, Los Angeles for TN secondary to tumors. The Barrow Neurological Institute (BNI) pain score was used to evaluate pain outcomes. RESULTS: Twelve patients were identified; 4 were male and 8 were female. Their mean age at treatment was 59.8 years (range, 47.7-84.7 years). Tumor pathologies included meningioma (n = 8), squamous cell carcinoma (n = 2), vestibular schwannoma (n = 1), and hemangiopericytoma (n = 1). No patient suffered from multiple sclerosis. Ten patients underwent initial radiation targeting their tumors-radiosurgery in 3 and fractionated radiation therapy in 7 others. Only 6 among these 10 experienced at least partial relief, which lasted a mean 6 months. Radiosurgery targeting the trigeminal nerve was eventually performed. Overall, 10 of 12 (83.3%) patients experienced good initial pain relief, complete in 6 (50%) patients. Pain recurred in 6 (60%) patients, at a mean 41 months after radiosurgery to the trigeminal nerve. Three patients experienced facial sensory dysfunction postprocedurally at a mean follow-up duration of 57 months. CONCLUSION: In contrast to tumor radiation, radiosurgery to the trigeminal nerve root resulted in reasonable and longer pain reduction, on par with the literature regarding surgical resection, with low risk of additional complications.

Adjuvant Stereotactic Radiosurgery and Radiation Therapy for the Treatment of Intracranial Chordomas.

Objective Chordomas are locally aggressive, highly recurrent tumors requiring adjuvant radiotherapy following resection for successful management. We retrospectively reviewed patients treated for intracranial chordomas with adjuvant stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Methods A total of 57 patients underwent 83 treatments at the UCLA Medical Center between February 1990 and August 2011. Mean follow-up was 57.8 months. Mean tumor diameter was 3.36 cm. Overall, 8 and 34 patients received adjuvant SRS and SRT, and the mean maximal dose of radiation therapy was 1783.3 cGy and 6339 cGy, respectively. Results Overall rate of recurrence was 51.8%, and 1- and 5-year progression-free survival (PFS) was 88.2% and 35.2%, respectively. Gross total resection was achieved in 30.9% of patients. Adjuvant radiotherapy improved outcomes following subtotal resection (5-year PFS 62.5% versus 20.1%; p = 0.036). SRS and SRT produced comparable rates of tumor control (p = 0.28). Higher dose SRT (> 6,000 cGy) (p = 0.013) and younger age (< 45 years) (p = 0.03) was associated with improved rates of tumor control. Conclusion Adjuvant radiotherapy is critical following subtotal resection of intracranial chordomas. Adjuvant SRT and SRS were safe and improved PFS following subtotal resection. Higher total doses of SRT and younger patient age were associated with improved rates of tumor control.

Lateralization of the Subthalamic Nucleus with Age in Parkinson's Disease.

Age-related changes in subthalamic nucleus (STN) position have not been well characterized in patients with Parkinson's disease (PD). We report a systematic retrospective analysis of age-related changes in radiographic and final deep brain stimulator (DBS) STN coordinates in PD patients. The charts of 134 PD patients (97 males, 28-84 years) representing 255 STN were reviewed. Multiple linear regression, stepwise regression, and relative importance of regressors analysis was performed to determine the significance of the relationship between STN position and age. Across all subjects, both radiographic STN localization and final DBS position within the STN showed a lateralization of the STN target with age (R2=0.1096,p=6.9×10-8 and R2=0.0433,p=8.7×10-4, respectively). Lateralization with age was observed regardless of MR field strength (1.5T and 3.0T) (R2=0.0946,p=7.6×10-6 and R2=0.2687,p=9.2×10-5, respectively). No other consistent or clinically significant age-related changes were identified. Multiple linear regression revealed that the third ventricle width and age are statistically significant predictors of radiographic STN lateralization (R2 = 0.2404, p = 1.51×10-5 and p = .00784 respectively). Step-wise regression demonstrated that age is a non-redundant predictor of STN lateralization relative to third ventricle width. Similar to healthy controls, STN position appears to shift laterally with age in PD. This highlights limitations of indirect targeting and atlas-based stereotactic surgery and argues for reliance on patient specific anatomy since factors such as age and 3rd ventricular width can contribute to patient-specific variability in STN localization.

Predictors of recurrence following resection of intracranial chordomas.

Management of intracranial chordomas remains challenging, despite improvements in microsurgical techniques and radiotherapy. Here, we analyzed the prognostic factors associated with improved rates of tumor control in patients with intracranial chordomas, who received either gross (GTR) or subtotal resections (STR). A retrospective review was performed to identify all patients who were undergoing resection of their intracranial chordomas at the Ronald Reagan University of California Los Angeles Medical Center from 1990 to 2011. In total, 57 patients undergoing 81 resections were included. There were 24 females and 33 males with a mean age of 44.6 years, and the mean tumor diameter was 3.36 cm. The extent of resection was not associated with recurrence. For all 81 operations, the 1 and 5 year progression free survival (PFS) was 87.5 and 40.4%, and 88.0 and 33.6% for STR and GTR, respectively (p=0.90). Adjuvant radiotherapy was associated with improved rates of PFS (hazard ratio [HR] 0.20; p=0.009). Additionally, age >45 years (HR 5.88; p=0.01) and the presence of visual deficits (HR 7.59; p=0.03) were associated with worse rates of tumor control. Tumor size, sex, tumor histology, and recurrent tumors were not predictors of recurrence. Younger age, lack of visual symptoms on presentation and adjuvant radiotherapy were associated with improved rates of tumor control following surgery. However, GTR and STR produced comparable rates of tumor control. The surgical management of intracranial chordomas should take a conservative approach, with the aim of maximal but safe cytoreductive resection with adjuvant radiation therapy, and a major focus on quality of life.

Effect of Cranial Window Diameter During Deep Brain Stimulation Surgery on Volume of Pneumocephalus.

OBJECTIVE: Successful deep brain stimulation (DBS) surgery necessitates high accuracy in targeting specific intracranial nuclei. Brain shift due to pneumocephalus can contribute to decreased accuracy. Larger burr holes and dural openings may increase pneumocephalus volume due to a greater degree of communication between the subdural space and extracranial air. The aim of this study is to determine if there is a statistically and clinically significant difference in postoperative pneumocephalus volume related to burr hole and durotomy size. MATERIALS AND METHODS: DBS electrodes were surgically implanted through either large (14 mm) burr holes or small (4 mm) twist drill holes. Immediate postoperative computerized tomography (CT) scans of 165 electrode implantations in 85 patients from 2010 to 2013 were retrospectively analyzed. Student's t-test and Mann-Whitney U-test were employed with a threshold of significance set at p ≤ 0.05. RESULTS: No significant difference in pneumocephalus was identified between patients who had implantation of DBS electrodes through 4 mm twist drill holes (N = 71 hemispheres, 12.84 ± 9.79 cm(3) ) and those with large 14 mm burr holes (N = 87, 11.70 ± 7.46 cm(3) , p = 0.42). Volume of pneumocephalus did not correlate with duration of surgery or patient age. The groups did not differ significantly with respect to other aspects of surgical implantation technique or surgical duration. CONCLUSION: While identifying factors that may reduce pneumocephalus volume may be critical to improving stereotactic accuracy and targeting, the current results suggest that burr hole size may not alter the degree of brain shift.

Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray area.

We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation.

(18)F-FDOPA PET for differentiating recurrent or progressive brain metastatic tumors from late or delayed radiation injury after radiation treatment.

UNLABELLED: Brain metastases are frequently treated with radiation. It is critical to distinguish recurrent or progressive brain metastases (RPBM) from late or delayed radiation injury (LDRI). The purpose of this study was to examine the diagnostic accuracy as well as the prognostic power of 6-(18)F-fluoro-l-dopa ((18)F-FDOPA) PET for differentiating RPBM from LDRI. METHODS: Thirty-two patients who had 83 previously irradiated brain metastases and who underwent (18)F-FDOPA PET because of an MR imaging-based suggestion of RPBM were studied retrospectively. PET studies were analyzed semiquantitatively (lesion-to-striatum and lesion-to-normal brain tissue ratios based on both maximum and mean standardized uptake values) and visually (4-point scale). The diagnostic accuracy of PET was verified by histopathologic analysis (n = 9) or clinical follow-up (n = 74) on a lesion-by-lesion basis. Receiver operating characteristic curve analysis was used to identify the best diagnostic indices. The power of (18)F-FDOPA PET to predict disease progression was evaluated with the Kaplan-Meier and Cox regression methods. RESULTS: The best overall accuracy was achieved by visual scoring, with which a score of 2 or more (lesion uptake greater than or equal to striatum uptake) resulted in a sensitivity of 81.3% and a specificity of 84.3%. Semiquantitative (18)F-FDOPA PET uptake indices based on lesion-to-normal brain tissue ratios were significantly higher for RPBM than for LDRI. Among the various predictors tested, (18)F-FDOPA PET was the strongest predictor of tumor progression (hazard ratio, 6.26; P < 0.001), and the lesion-to-normal brain tissue ratio or visual score was the best discriminator. The mean time to progression was 4.6 times longer for lesions with negative (18)F-FDOPA PET results than for lesions with positive (18)F-FDOPA PET results (76.5 vs. 16.7 mo; P < 0.001). (18)F-FDOPA PET findings tended to predict overall survival. CONCLUSION: Metabolic imaging with (18)F-FDOPA PET was useful for differentiating RPBM from LDRI. Semiquantitative indices, particularly lesion-to-normal uptake ratios, could be used. A visual score comparing tumor (18)F-FDOPA uptake and striatum (18)F-FDOPA uptake provided the highest sensitivity and specificity and was predictive of disease progression.

Deep brain stimulator-induced diaphoresis in Parkinson's disease patients.

We report an unusual finding of bilateral facial and corporeal diaphoresis and sensation of heat during deep brain stimulation in two patients. Stimulation of the hypothalamospinal tract located medial to the subthalamic nucleus is likely to be responsible for this side effect.

Stereotactic radiation therapy for progressive residual pilocytic astrocytomas.

This report shows the results of stereotactic radiation therapy for progressive residual pilocytic astrocytomas. Medical records of patients who had undergone stereotactic radiation therapy for a progressive residual pilocytic astrocytoma were reviewed. Between 1995 and 2010, 12 patients with progression of a residual pilocytic astrocytoma underwent stereotactic radiation therapy at UCLA. Presentation was headache (4), visual defects (3), hormonal disturbances (2), gelastic seizures (2) and ataxia (1). MRI showed a cystic (9), mixed solid/cystic (2) or solid tumor (1); located in the hypothalamus (5), midbrain (3), thalamus (2), optic chiasm (1) or deep cerebellum (1). Median age was 21 years (range 5-41). Nine tumors received stereotactic radiotherapy (SRT). Three tumors received stereotactic radiosurgery (SRS), two of them to their choline positive regions. SRT median total dose was 50.4 Gy (40-50.4 Gy) in a median of 28 fractions (20-28), using a median fraction dose of 1.8 Gy (1.8-2 Gy) to a median target volume of 6.5 cm(3). (2.4-33.57 cm(3)) SRS median dose was 18.75 Gy (16.66-20 Gy) to a median target volume of 1.69 cm(3) (0.74-2.22 cm(3)). Median follow-up time was 37.5 months. Actuarial long-term progression-free and disease-specific survival probabilities were 73.3 and 91.7 %, respectively. No radiation-induced complications were observed. Stereotactic radiation therapy is a safe and effective modality to control progressive residual pilocytic astrocytomas. Better outcomes are obtained with SRT to entire tumor volumes than with SRS targeting choline positive tumor regions.

Multi-institutional evaluation of deep brain stimulation targeting using probabilistic connectivity-based thalamic segmentation.

OBJECT: Due to the lack of internal anatomical detail with traditional MR imaging, preoperative stereotactic planning for the treatment of tremor usually relies on indirect targeting based on atlas-derived coordinates. The object of this study was to preliminarily investigate the role of probabilistic tractography-based thalamic segmentation for deep brain stimulation (DBS) targeting for the treatment of tremor. METHODS: Six patients undergoing bilateral implantation of DBS electrodes in the thalamus for the treatment of upper-extremity tremor were studied. All patients underwent stereotactic surgical implantation using traditional methods (based on indirect targeting methodologies and intraoperative macrostimulation findings) that were programmed for optimal efficacy, independent of tractography-based segmentations described in this report. Connectivity-based thalamic segmentations were derived by identifying with which of 7 cortical target regions each thalamic voxel had the highest probability of connectivity. The authors retrospectively analyzed the location of the optimal contact for treatment of tremor with connectivity-based thalamic segmentations. Findings from one institution (David Geffen School of Medicine at UCLA) were validated with results from 4 patients at another institution (University of Virginia Health System). RESULTS: Of 12 electrodes implanted using traditional methodologies, all but one resulted in efficacious tremor control. Connectivity-based thalamic segmentation consistently revealed discrete thalamic regions having unique connectivity patterns with distinct cortical regions. Although the authors initially hypothesized that the most efficacious DBS contact for controlling tremor would colocalize with the thalamic region most highly connected with the primary motor cortex, they instead found it to highly colocalize with those thalamic voxels demonstrating a high probability of connectivity with premotor cortex (center-to-center distance: 0.36 ± 0.55 mm). In contrast to the high degree of colocalization with optimal stimulation site, the precise localization of the premotor cortex-defined thalamic region relative to the anterior and posterior commissures was highly variable. Having defined a connectivity-based target for thalamic stimulation in a cohort of patients at David Geffen School of Medicine at UCLA, the authors validated findings in 4 patients (5 electrodes) who underwent surgery at a different institution (University of Virginia Health System) by a different surgeon. CONCLUSIONS: This report identifies and provides preliminary external validation of a novel means of targeting a patient-specific therapeutic thalamic target for the treatment of tremor based on individualized analysis of thalamic connectivity patterns. This novel thalamic targeting approach is based on identifying the thalamic region with the highest probability of connectivity with premotor and supplementary motor cortices. This approach may prove to be advantageous over traditional preoperative methods of indirect targeting, providing patient-specific targets that could improve the precision, efficacy, and efficiency of deep brain stimulation surgery. Prospective evaluation and development of methodologies to make these analyses more widely available to neurosurgeons are likely warranted.

Accuracy of frame-based stereotactic magnetic resonance imaging vs frame-based stereotactic head computed tomography fused with recent magnetic resonance imaging for postimplantation deep brain stimulator lead localization.

BACKGROUND: Introduction of the portable intraoperative CT scanner provides for a precise and cost-effective way of fusing head CT images with high-tesla MRI for the exquisite definition of soft tissue needed for stereotactic targeting. OBJECTIVE: To evaluate the accuracy of stereotactic electrode placement in patients undergoing deep brain stimulation (DBS) by comparing frame-based postimplantation intraoperative CT (iCT) images fused to a recent 3T-MRI with frame-based postimplantation intraoperative MRI (iMRI) alone. METHODS: Frame-based DBS surgeries of 46 targets performed from February 8, 2007 to April 28, 2008 in 26 patients with the use of immediate postimplantation iMRI for target localization were compared with frame-based immediate postimplantation iCT fused with a recent 3T brain MRI for DBS localization of 50 targets performed from August 13, 2008 to February 18, 2010 in 26 patients. Pre- and postoperative mid anterior commissure-posterior commissure line coordinates and XYZ coordinates for preoperatively calculated DBS targets (intended target) and for the permanent DBS lead tips were determined. The differences between preoperative DBS target and postoperative permanent DBS lead-tip coordinates based on postimplantation intraoperative MRI for the MRI-alone group and based on postimplantation intraoperative CT fused to recent preoperative MRI in the CT-MRI group were measured. The t test and Yuen test were used for comparison. RESULTS: No statistically significant differences were found between the 2 groups when comparing the pre- and postperative changes in mid anterior commissure-posterior commissure line coordinates and XYZ coordinates. CONCLUSION: Postimplantation DBS lead localization and therefore targeting accuracy was not significantly different between frame-based stereotactic 1.5T-MRI and frame-based stereotactic head CT fused with recent 3T-MRI.

A review of low-intensity focused ultrasound pulsation.

With the recent approval by the Food and Drug Administration (FDA) of Deep Brain Stimulation (DBS) for Parkinson's Disease, dystonia and obsessive compulsive disorder (OCD), vagus nerve stimulation (VNS) for epilepsy and depression, and repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression, neuromodulation has become increasingly relevant to clinical research. However, these techniques have significant drawbacks (eg, lack of special specificity and depth for the rTMS, and invasiveness and cumbersome maintenance for DBS). This article reviews the background, rationale, and pilot studies to date, using a new brain stimulation method-low-intensity focused ultrasound pulsation (LIFUP). The ability of ultrasound to be focused noninvasively through the skull anywhere within the brain, together with concurrent imaging (ie, functional magnetic resonance imaging [fMRI]) techniques, may create a role for research and clinical use of LIFUP. This technique is still in preclinical testing and needs to be assessed thoroughly before being advanced to clinical trials. In this study, we review over 50 years of research data on the use of focused ultrasound (FUS) in neuronal tissue and live brain, and propose novel applications of this noninvasive neuromodulation method.

Diffusion tensor imaging and colored fractional anisotropy mapping of the ventralis intermedius nucleus of the thalamus.

BACKGROUND: The ventralis intermedius (VIM) nucleus of the thalamus is the primary surgical target for treatment of tremor. Most centers rely on indirect targeting based on atlas-defined coordinates rather than patient-specific anatomy, making intraoperative physiological mapping critical. Detailed identification of this target based on patient-specific anatomic features can help optimize the surgical treatment of tremor. OBJECTIVE: To study colored fractional anisotropic images and diffusion tensor imaging (DTI) tractography to identify characteristic magnetic resonance appearances of the VIM nucleus. METHODS: Four patients undergoing stereotactic surgery for essential tremor (ET) were retrospectively studied with analysis of magnetic resonance imaging-based colored fractional anisotropy (FA) images and fiber tractography. All were scanned with a 1.5-T magnetic resonance imaging unit, and all sequences were obtained before frame placement. Because the goal of this study was to identify the DTI characteristics of physiologically defined VIM nucleus, we selected and studied patients who had undergone DTI and had efficacious tremor control with intraoperative microlesioning effect and tremor reduction with less than 2.0-V stimulation. RESULTS: Analysis of color FA maps, which graphically illustrate fiber directionality, revealed consistent anatomic patterns. The region of the VIM nucleus can be seen as an intermediate region where there is a characteristic transition of color. Presumptive VIM nucleus interconnectivity with sensorimotor cortex and cerebellum was identified via the internal capsule and the superior cerebellar peduncle, respectively. FA maps could also be used to distinguish segments of gray matter, white matter, and gray-white matter boundaries. CONCLUSION: Analysis of DTI and FA maps on widely available 1.5-T magnetic resonance imaging yields clear identification of various structures key to neurosurgical targeting. Prospective evaluation of integrating DTI into neurosurgical planning may be warranted.

Pineocytoma with diffuse dissemination to the leptomeninges.

Pineal parenchymal tumors are rare. Of the three types of pineal parenchymal tumors, pineocytomas are the least aggressive and are not known to diffusely disseminate. In this paper, we report the successful treatment of a case of pineocytoma with diffuse leptomeningeal relapse following initial stereotactic radiotherapy. A 39-year-old female presented with headaches, balance impairment, urinary incontinence, and blunted affect. A pineal mass was discovered on magnetic resonance imaging (MRI). A diagnosis of pineocytoma was established with an endoscopic pineal gland biopsy, and the patient received stereotactic radiotherapy. Ten years later, she developed diffuse leptomeningeal dissemination. The patient was then successfully treated with craniospinal radiation therapy. Leptomeningeal spread may develop as late as 10 years after initial presentation of pineocytoma. Our case demonstrates the importance of long-term follow-up of patients with pineal parenchymal tumors following radiation therapy, and the efficacy of craniospinal radiation in the treatment of leptomeningeal dissemination.

Diffusion tensor imaging (DTI) and colored fractional anisotropy (FA) mapping of the subthalamic nucleus (STN) and the globus pallidus interna (GPi).

INTRODUCTION: The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are the most common surgical targets for the treatment of Parkinson's disease. We studied directionally colored fractional anisotropy (FA) and diffusion tensor imaging (DTI) sequences to better target these anatomical regions. METHODS: Four patients undergoing stereotactic surgery for movement disorders were studied. Stereotactic targets and fiber tractography were determined on MRIs using the Schaltenbrand-Wahren atlas for definition in the iPlan software. In addition, post-operative imaging was fused to preoperative FA sequences for end-result identification. Axial, sagittal, and coronal images of the FA sequence were studied. DTI parameters used ranged from 2 to 4 mm for voxel size in the x/y/z planes, fiber length was kept constant at 15 mm and FA threshold of 0.25. RESULTS: Colored FA maps resulted in a key signature in and around the STN and GPi. Regions identified include, but were not limited to: the internal capsule, nigral projections, the thalamic fasciculus, Forel's fields H1 and H2, zona incerta, suthalamic fasciculus, tegmental tracts, and cerebello-rubro-thalamic tract. CONCLUSIONS: Colored FA maps allow a potential method to identify the STN and GPi accurately. DTI has proven to be a powerful tool that can be used to augment identification of the STN nucleus and GPi used for stereotactic surgery.

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

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.

Endonasal transsphenoidal surgery and multimodality treatment for giant pituitary adenomas.

OBJECTIVE: Giant pituitary adenomas (> or =40 mm) pose a major management challenge. We describe the experience of a single surgeon and a dedicated neuro-endocrine team with multimodality treatment of these tumours in three specialized institutions. DESIGN: Retrospective data set analyses. PATIENTS: Fifty-one consecutive patients with a giant adenoma (39 endocrine-inactive, 12 endocrine-active; mean tumour diameter 45 mm) treated over 10 years by an endonasal transsphenoidal approach were included. All patients had surgical resection followed by radiotherapy and/or medical therapy as judged necessary. MEASUREMENTS: Hormonal and visual status, extent of resection, tumour control rates, complications and use of medical and radiotherapy were evaluated. RESULTS: Surgery resulted in gross total, near total and subtotal removal in21 (41%), 10 (20%) and 20 (39%) patients respectively. Complete tumour removal was associated with absence of cavernous sinus invasion (P < 0.001). Long-term endocrine function improved in 49% of patients and new endocrinopathy occurred in 14.6%; 76% required long-term hormone replacement therapy. Vision improved in 81.5% of the patients and there was no visual worsening. At the last follow up (median 30 months), tumour control was achieved in 96% of patients: 59% with surgery alone, 20% with surgery plus focussed radiotherapy, 18% with surgery and medical therapy and two with all three modalities. CONCLUSIONS: Endonasal surgery provides effective initial treatment for patients with giant adenomas. Multimodality therapy was needed in almost 50% of patients and this rate will likely increase with longer follow up. Close collaboration of neurosurgeons with endocrinologists and radiation oncologists is essential for optimal treatment of patients with these challenging tumours.

Initial clinical experience with image-guided linear accelerator-based spinal radiosurgery for treatment of benign nerve sheath tumors.

BACKGROUND: Stereotactic radiosurgery has proven a safe and effective treatment of cranial nerve sheath tumors. A similar approach should be successful for histologically identical spinal nerve sheath tumors. METHODS: The preliminary results of linear accelerator-based spinal radiosurgery were retrospectively reviewed for a group of 25 nerve sheath tumors. Tumor location was cervical 11, lumbar 10, and thoracic 4. Thirteen tumors caused sensory disturbance, 12 pain, and 9 weakness. Tumor size varied from 0.9 to 4.1 cm (median, 2.1 cm). Radiosurgery was performed with a 60-MV linear accelerator equipped with a micro-multileaf collimator. Median peripheral dose and prescription isodose were 12 Gy and 90%, respectively. Image guidance involved optical tracking of infrared reflectors, fusion of amorphous silicon radiographs with dynamically reconstructed digital radiographs, and automatic patient positioning. Follow-up varied from 12 to 58 months (median, 18). RESULTS: There have been no local failures. Tumor size remained stable in 18 cases, and 7 (28%) demonstrated more than 2 mm reduction in tumor size. Of 34 neurologic symptoms, 4 improved. There has been no clinical or imaging evidence for spinal cord injury. One patient had transient increase in pain and one transient increase in numbness. CONCLUSIONS: Results of this limited experience indicate linear accelerator-based spinal radiosurgery is feasible for treatment of benign nerve sheath tumors. Further follow-up is necessary, but our results imply spinal radiosurgery may represent a therapeutic alternative to surgery for nerve sheath tumors. Symptom resolution may require a prescribed dose of more than 12 Gy.