Robot-Assisted Stereotactic Shunting as a Novel Treatment for Pontine Glioependymal Cysts.

In this case report, the authors describe the first case of a glioependymal cyst of the brainstem managed by robot-assisted, stereotactic, cysto-ventricular shunting. Glioependymal cysts are rare congenital cystic lesions that are thought to form by displacement of ependymal cells during the embryonal period. Glioependymal cysts have been reported in a variety of different locations within the central nervous system. However, glioependymal cysts of the brainstem have only been described once before. Here, we report the case of a 53-year-old man who was referred to our department due to hemiparesis, hemihypesthesia, and hemidysesthesia, as well as facial and abducens nerve palsy. A large pontine glioependymal cyst was confirmed via magnetic resonance imaging (MRI) scans. The cyst was subsequently decompressed by connecting the cyst with the fourth ventricle via robot-assisted stereotactic shunt placement. In the postoperative course, the patient made a quick recovery and did not report any permanent neurologic deficits.

Investigating the Existence of Ribosomal Protein L5 Gene in Syrian Strain of Leishmania tropica Genome: Sequencing It and Evaluating Its Immune Response as DNA Vaccine.

Cutaneous leishmaniasis in Syria is caused mainly by Leishmania tropica. It represents a serious health problem, which has aggravated further after the civil war in the country. Until now, there are no effective protective strategies, safe therapy, or efficacious vaccine to protect from this infection. DNA vaccines represent a promising approach for achieving protection against leishmaniasis. The L5 ribosomal protein plays fundamental roles in the assembly process of the ribosome subunits, so this study has chosen the ribosomal protein L5 gene to design a DNA vaccine against Leishmania tropica infection. After proving the existence of the ribosomal protein L5 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), it was sequenced and cloned into a pCI plasmid, and the designed DNA vaccine was administered to BALB/c mice. The protective response was evaluated by measuring lesion development in immunized BALB/c mice for 6 weeks after challenging mice with the parasite. RT-qPCR was used to quantify IL-12, IFN-γ, and IL-4 in draining lymph nodes (DLNs) of immunized mice. In the final week, the parasite burden was determined in footpad lesions and local draining lymph nodes (DLNs). This study demonstrated the presence and expression of the ribosomal protein L5 gene in the Syrian strain of Leishmania tropica promastigotes. The sequence of the ribosomal protein cDNA L5 gene was determined and published in Genbank. The gene size was 918 bp. Expression was also demonstrated at the level of cDNA. This study also demonstrated that vaccination with the ribosomal protein L5 gene induces TH1 response in immunized mice. This response prevents the partial development of a skin lesion of Leishmania.

Analysis of Driver Mutational Hot Spots in Blood-Derived Cell-Free DNA of Patients with Primary Central Nervous System Lymphoma Obtained before Intracerebral Biopsy.

In newly diagnosed systemic diffuse large B-cell lymphoma, next-generation sequencing of plasma-derived cell-free DNA (cfDNA) detects somatic mutations as accurate as genotyping of the tumor biopsy. A distinct diffuse large B-cell lymphoma entity confined to the central nervous system is primary central nervous system lymphoma (PCNSL), which requires intracerebral biopsy and neuropathologic analysis to establish the diagnosis. So far, a biomarker for diagnosis and follow-up of PCNSL that can be investigated in blood has not been identified. This article addresses the question whether somatic mutations of the CD79B and MYD88 driver genes of PCNSL can be detected in cfDNA at disease diagnosis. Stereotactic biopsies and cfDNA of 27 PCNSL patients were analyzed for CD79B and MYD88 mutations. As control, cfDNA derived from six healthy volunteers was used. CD79B and MYD88 hot spot mutations were identified in 16 of 27 (59%) and 23 of 27 (85%) PCNSL biopsies, respectively, but only in 0 of 27 (0%) and 1 of 27 (4%) corresponding cfDNA samples, respectively. In cfDNA of one of four patients with Waldenstrom disease, as a further control, the MYD88 L265P mutation was readily detected, despite complete clinical remission. These data suggest that in PCNSL even if they carry such mutations, alterations of CD79B and MYD88 cannot be reliably detected in blood-derived cfDNA obtained before intracerebral biopsy.

Evaluation of Immune Response and Protection Induced by V-ATPase Subunit F as DNA Vaccine Against Leishmania tropica (LCED Syrian 01) After Detection and Sequencing.

BACKGROUND: Leishmaniasis is one of the major emerging health problems worldwide and Leishmania tropica (L. tropica) is most prevalent in the Middle East due to conflict and environmental factors, and there is no effective prevention strategy available until now. An effective vaccine has not been developed to date. DNA vaccines are considered a promising approach to protect against this infection. In this study, since vacuolar (H+)-ATPase (V-ATPase) enzyme has an essential role in the life cycle of eukaryotes, V-ATPase subunit F gene has been chosen to design DNA vaccine and evaluate its immunogenicity in BALB\c mice. METHODS: Genomic DNA was isolated from promastigote culture, synthesized complementary DNA (cDNA) after standardization of Polymerase Chain Reaction (PCR) conditions. The V-ATPase subunit F gene was placed into plasmid PCI. Then, recombinant plasmids were transformed into competent cells. Cloning was confirmed by PCR, restriction enzyme assays, and finally, DNA sequence analysis, after making miniprep from positive colonies and finally the gene was sequenced. BALB/c mice were immunized subcutaneously three times at an interval of two weeks with designed vaccine. BALB\c mice were challenged with 106 promastigotes of L. tropica 7 days post-immunization. IL-12, IFN-γ and IL-4 were quantified by RT-qPCR. RESULTS: The present study proved the existence of subunit F gene in Syrian strain of L. tropica (LCED Syrian 01) promastigotes genome. Its expression was also proved in these parasites and the gene length was 414 bp. CONCLUSION: This study showed that vaccination of BALB\c mice with this gene induced partial protection against Leishmania by reduction of lesion size by 41.9% and parasite burden reduction by 3-log in the dLNs when compared with control group. IFN-γ\IL-4 was 1.6 after challenge test, so the immune response consisted of both Th1 and Th2.

High-Resolution O-Arm Data Reconstruction for Optimized Intraoperative Imaging of Deep Brain Stimulation Leads: A Preclinical Study.

BACKGROUND: The employment of the O-arm for intraoperative localization of deep brain stimulation (DBS) leads has been shown to be feasible and effective. However, partial volume artifacts impede the determination of individual electrode contacts and thus allow only an indirect approximation of each contact's localization. OBJECTIVE: To reduce the partial volume artifacts by means of high-resolution (HiRes) reconstruction of O-arm data and thus allow more accurate predictions with regard to the positioning and orientation of individual DBS contacts. METHODS: Following intraoperative flat-panel computed tomography, the O-arm raw data were reconstructed with a resolution of 0.2 mm × 0.2 mm × 0.2 mm. The geometric integrity of HiRes reconstructions was assessed via landmark transformation. Using a phantom, resolutions of both reconstruction modalities were then evaluated by means of the modulation transfer function (MTF). Finally, directional and nondirectional leads were compared visually to analyze the delineation of individual electrode contacts. RESULTS: With a mean accuracy of 0.56 mm ± 0.12 mm, geometric integrity remained intact during HiRes reconstruction. Analysis of HiRes reconstruction resolution yielded a 47.7% increase of the 10% MTF in comparison to conventional postprocessing. Reduction of partial volume artifacts yielded strong contrasts of electrode compartments and allowed direct identification of individual contacts as well as localization of the X-ray marker on directional leads. CONCLUSION: HiRes reconstruction of O-arm data allows an effective reduction of partial volume artifacts to such an extent that a delineation of individual contacts across single DBS leads is possible without requiring increases in radiation dose.

10 kHz cervical SCS for chronic neck and upper limb pain: 12 months' results.

OBJECTIVE: Spinal Cord Stimulation (SCS) overlaps painful areas with paresthesia to alleviate pain. Ten kHz High-Frequency SCS (HF10 cSCS) constitutes a treatment option that can provide pain relief without inducing paresthesia. In this retrospective, open-label study, we evaluated the efficacy of HF10 cSCS in chronic neck and/or upper limb pain. METHODS: Between May 2015 and August 2017, 24 consecutive patients with neck and/or upper limb pain were treated with HF10 cSCS. The patients' mean age was 61.4 years (range: 40.1-82.6 years). The mean neck and upper limb pain at baseline was 8.8 (range: 7.0-10) and 7.5 (range: 6.0-9.0) according to the visual analog scale (VAS). Functionality was evaluated using the Oswestry Disability Index (ODI). To assess health-related psychological impairment, we used the Global Assessment of Functioning questionnaire. RESULTS: Twenty-three patients responded to treatment. Pain intensity reduced significantly to a mean score of VAS 2.5 (range: 2.0-4.0) for neck and 2.0 (range: 1.0-3.0) for upper limb pain after 6 months. At 12 months, VAS scores for neck and upper limb pain reduced to 2.2 (range: 1.0-3.0) and 1.7 (range: 1.0-3.0), respectively. Mean ODI scores decreased from 31 (range: 21-42) at baseline to 19.9 (range: 8-26) after 12 months. In three patients, infection of the IPG pocket occurred r and 8.7 months after surgery. One patient has had lead migration resulting in a surgical revision. INTERPRETATION: HF10 cSCS therapy has proven to be effective in reducing neck and upper limb pain significantly and increasing functional capacity. These results warrant further studies with larger patient series and longer follow-ups.

Combined Deep Brain Stimulation of Subthalamic Nucleus and Ventral Intermediate Thalamic Nucleus in Tremor-Dominant Parkinson's Disease Using a Parietal Approach.

OBJECTIVES: Despite its efficacy in tremor-suppression, the ventral intermediate thalamic (VIM) nucleus has largely been neglected in deep brain stimulation (DBS) for tremor-dominant Parkinson's disease (tdPD). The employment of a parietal approach, however, allows stimulation of VIM and subthalamic nucleus (STN) using one trajectory only and thus constitutes a promising alternative to existing strategies. In the present study, we investigate safety and efficacy of combined lead implantation and stimulation of STN and VIM using a parietal approach. MATERIALS AND METHODS: Retrospective analysis of five patients with tdPD was performed who underwent DBS using a parietal approach. Changes in symptom severity, disease-specific health-related quality of life and l-dopa equivalent doses (LED) were evaluated over a total time course of 12 months. RESULTS: DBS within both targets yielded significant improvement of parkinsonian symptoms (median: 40.0%, p = 0.04) in the first 6 months of continuous stimulation and remained stable thereafter (median improvement at 12 months: 43.2%, p = 0.07). Sustained improvement of tremor (median at 6 months: 100.0%, p = 0.04; median at 12 months 83.3%, p = 0.04) and quality of life scores (median at 6 months: 29.8%, p = 0.04; median at 12 months: 32.6%, p = 0.04) was noted throughout the follow-up period. No significant change of LEDs was observed by the end of follow-up (median decrease: 2.2%, p = 0.89). CONCLUSIONS: Simultaneous DBS of VIM and STN using one trajectory is safe, yielding good control of parkinsonian tremors. Further studies, however, are necessary to determine whether a parietal trajectory affords better control over tremor symptoms than established strategies and hence justifies the potential risks associated with the alternative approach.

A multicenter real-world review of 10 kHz SCS outcomes for treatment of chronic trunk and/or limb pain.

Objectives: High-frequency spinal cord stimulation (HF-SCS) at 10 kHz has proven to be efficacious in the treatment of chronic back and leg pain in a randomized, controlled, trial (SENZA-RCT). However, large observational studies have yet to be published. Therefore, we performed a real-world, multicenter, retrospective, review of therapy efficacy in 1660 patients with chronic trunk and/or limb pain. Methods: Data were collected in a real-world environment and retrospectively sourced from a global database. Included patients were trialed and/or permanently implanted with HF-SCS at 10 kHz between April 2014 and January 2018. We evaluated responder rates at 3, 6, and 12 months post-implantation. Response was defined as ≥50% pain relief from baseline. A last visit analysis included responder rate along with overall change in function, sleep, quality of life, and medication intake versus baseline. Results: Eighty-four percent of our HF-SCS-treated patients had both chronic back and leg pain. At least 70% of patients reported response to therapy throughout 12 months of follow-up. This sustained responder rate was corroborated by the last visit value (74.1%). Most patients reported concomitant improvements in function (72.3%), sleep (68.0%), and quality of life (90.3%) at their last visit versus baseline. Thirty-two percent of patients reported decreased medication intake at their last visit. Interpretation: Sustained and effective pain relief was experienced by >70% of our HF-SCS-treated patients, consistent with the findings of a previously published randomized, controlled, trial. Our review provides complementary evidence to support the treatment of chronic back and leg pain with this therapy.

Determining the Rotational Orientation of Directional Deep Brain Stimulation Leads Employing Flat-Panel Computed Tomography.

BACKGROUND: Directional deep brain stimulation (DBS) constitutes an emerging technology that allows selective stimulation of target structures via partitioned electrode contacts. In order to effectively perform target-tailored stimulation, knowledge of the rotational orientation of the segmented leads is imperative. OBJECTIVE: To develop a universally applicable and reliable method for determination of lead orientation angles in DBS using flat-panel computed tomography (fpCT). METHODS: A binary template of directional leads DB-2202-30 (Boston Scientific, Natick, Massachusetts) and 6170 (Abbott, Plano, Texas) was imported into the 2-dimensional raw data set of a conventional fpCT scan. The template was aligned with and manually rotated around the predetermined lead trajectory. The overall orientation of the segmented lead can be deduced by transferring position and orientation of the lead orientation marker into the 3-dimensional volume. Accuracy of the method was investigated by two raters in a phantom study. RESULTS: Accuracy were 5.4° ± 4.1° (range: 0.4°-11.9°) for rater 1 and 5.2° ± 3.0° (range: 0.3°-10.2°) for rater 2, when investigating DB-2202-30. For 6170 observed deviations were 2.5° ± 1.7° (range: 0.2°-5.2°) and 4.3° ± 3.6° (range: 0.2°-11.2°) for raters 1 and 2, respectively. CONCLUSION: fpCT imaging constitutes a precise and accurate means to determine the rotational orientation of directional leads. The approach is universally transferable to different electrode designs as the template can easily be adjusted to the electrodes' specific measures. The approach is independent from polar implantation angles owing to fpCT- and methodological features.

A Retrospective Case Series of High-Frequency Spinal Cord Stimulation (HF10-SCS) in Neurogenic Bladder Incontinence.

BACKGROUND: Current treatment options for bladder disorders of neurogenic etiology often leave unsatisfactory results. Therefore, new and effective treatments must be investigated. High-frequency spinal cord stimulation (HF-SCS) at 10 kHz has proven to be effective in the treatment of refractory chronic back and leg pain. OBJECTIVE: To evaluate the efficacy of HF-SCS at 10 kHz in alleviating lower urinary tract dysfunction and bladder incontinence in 5 patients with underlying neurological disease or spinal cord injury, through retrospective study. METHODS: Urodynamic parameters such as voiding frequency, residual volume, episodes of incontinence, and the patients' subjective impression impairment of life were assessed and compared pre- and postoperatively. Reduction in pain intensity was assessed as change on the Numeric Rating Scale (NRS). RESULTS: All 5 patients had significantly positive outcomes. Episodes of leakage per day improved by 83% on average. Quality of life questionnaires and subjective bother scale revealed an improvement of 36% and 57%, respectively. Individual symptoms among the patient group such as residual volume also responded to the treatment as well. Mean pain NRS of 8.6 cm was reduced to 3.9 cm (55%) at 6 mo follow-up. CONCLUSION: HF-SCS at 10 kHz significantly alleviated symptoms of neurogenic bladder incontinence in patients suffering from neurological disease or spinal cord injury. However, larger and prospective, randomized studies are necessary to make a clear statement regarding the efficacy of this therapy in lower urinary tract dysfunction and bladder incontinence.

Comparative Study of Robot-Assisted versus Conventional Frame-Based Deep Brain Stimulation Stereotactic Neurosurgery.

BACKGROUND/AIMS: Technological advancements had a serious impact on the evolution of robotic systems in stereotactic neurosurgery over the last three decades and may turn robot-assisted stereotactic neurosurgery into a sophisticated alternative to purely mechanical guiding devices. OBJECTIVES: To compare robot-assisted and conventional frame-based deep brain stimulation (DBS) surgery with regard to accuracy, precision, reliability, duration of surgery, intraoperative imaging quality, safety and maintenance using a standardized setup. METHODS: Retrospective evaluation of 80 consecutive patients was performed who underwent DBS surgery using either a frame-based mechanical stereotactic guiding device (n = 40) or a stereotactic robot (ROSA Brain, MedTech, Montpellier, France) (n = 40). RESULTS: The mean accuracy of robot-assisted and conventional lead implantation was 0.76 mm (SD: 0.37 mm, range: 0.17-1.52 mm) and 1.11 mm (SD: 0.59 mm, range: 0.10-2.90 mm), respectively. We observed a statistically significant difference in accuracy (p < 0.001) when comparing lateral deviations between both modalities. Furthermore, a statistical significance was observed when investigating the proportion of values exceeding 2.00 mm between both groups (p = 0.013). In 8.75% (n = 7) of conventionally implanted leads, lateral deviations were greater than 2.0 mm. With a maximum value of 1.52 mm, this threshold was never reached during robot-guided DBS. The mean duration of DBS surgery could be reduced significantly (p < 0.001) when comparing robot-guided DBS (mean: 325.1 ± 81.6 min) to conventional lead implantation (mean: 394.8 ± 66.6 min). CONCLUSIONS: Robot-assisted DBS was shown to be superior to conventional lead implantation with respect to accuracy, precision and operation time. Improved quality control, continuous intraoperative monitoring and less manual adjustment likely contribute to the robotic system's reliability allowing high accuracy during lead implantation despite limited experience. Hence, robot-assisted lead implantation can be considered an appropriate and reliable alternative to purely mechanical devices.

Deep brain stimulation is effective in pediatric patients with GNAO1 associated severe hyperkinesia.

BACKGROUND: Exacerbation of hyperkinesia is a life-threatening complication of dyskinetic movement disorders, which can lead to multi-organ failure and even to death. GNAO1 has been recently identified to be involved in the pathogenesis of early infantile epileptic encephalopathy and movement disorders. Patients with GNAO1 mutations can present with a severe, progressive hyperkinetic movement disorder with prolonged life-threatening exacerbations, which are refractory to most anti-dystonic medication. OBJECTIVE: The objective was to investigate the evolution of symptoms and the response to deep brain stimulation of the globus pallidus internus (GPi-DBS) in patients with different GNAO1 mutations. METHODS: We report six patients presenting with global motor retardation, reduced muscle tone and recurrent episodes of severe, life-threatening hyperkinesia with dystonia, choreoathetosis, and ballism since early childhood. Five of them underwent GPi-DBS. RESULTS: The genetic workup revealed mutations in GNAO1 for all six patients. These encompass a new splice site mutation (c.723+1G>T) in patient 1, a new missense mutation (c.610G>C; p.Gly204Arg) in patient 2, a heterozygous mutation (c.625>T; p.Arg209Cys) in patients 3 and 4, and a heterozygous mutation (c.709G>A; p.Glu237Lys) in patients 5 and 6. By intervention with GPi-DBS the severe paroxysmal hyperkinetic exacerbations could be stopped in five patients. One patient is still under evaluation for neuromodulation. CONCLUSION: In complex movement disorders of unsolved etiology clinical WES can rapidly streamline pathogenic genes. We identified two novel GNAO1 mutations. GPi-DBS can be an effective and life-saving treatment option for patients with GNAO1 mutations and has to be considered early.

Neuroanatomical background and functional considerations for stereotactic interventions in the H fields of Forel.

The H fields of Forel constitute an intricate neuroanatomical structure that occupies a central position within the posterior subthalamus. Anatomically, it features a dense concentration of fiber bundles including corticofugal, pallidothalamic, cerebellothalamic and other projections that connect functionally relevant areas of the brain. Functionally, the fields of Forel are embedded within the cortico-striato-thalamo-cortical circuit and constitute the main link between the striatopallidal system and the thalamocortical network. Given the current understanding of basal ganglia involvement in movement disorders and neuropsychiatric disease we sought to investigate the H fields of Forel as a potential target in stereotactic functional neurosurgery. Although historically recognized in the treatment of movement disorders, behavioral disorders and epilepsy, the significance of the H fields is considerably diminished today receiving only little attention. Owing to the current lack of reviews addressing the anatomical and functional organization of Forel's fields, we aim to deliver an up-to-date overview of the H fields in this paper. We investigate the complex neuroanatomy and describe the passage of the various fiber systems that course through the posterior subthalamus. We revise the role of Forel's fields in the current context of our understanding of cortico-basal ganglia circuitry and discuss the historic relevance of Forel's fields during the lesional era. Finally, we provide an outlook regarding the potential of deep brain stimulation in close proximity and within the H fields of Forel.

Causes of failure of pallidal deep brain stimulation in cases with pre-operative diagnosis of isolated dystonia.

INTRODUCTION: Pallidal deep brain stimulation (GPi-DBS) is an effective therapy for isolated dystonia, but 10-20% of patients show improvement below 25-30%. We here investigated causes of insufficient response to GPi-DBS in isolated dystonia in a cross-sectional study. METHODS: Patients with isolated dystonia at time of surgery, and <30% improvement on the Burke-Fahn-Marsden dystonia-rating-scale (BFMDRS) after ≥6 months of continuous GPi-DBS were videotaped ON and OFF stimulation, and history, preoperative videos, brain MRI, medical records, stimulation settings, stimulation system integrity, lead location, and genetic information were obtained and reviewed by an expert panel. RESULTS: 22 patients from 11 centres were included (8 men, 14 women; 9 generalized, 9 segmental, 3 focal, 1 bibrachial dystonia; mean (range): age 48.7 (25-72) years, disease duration 22.0 (2-40) years, DBS duration 45.5 (6-131) months). Mean BFMDRS-score was 31.7 (4-93) preoperatively and 32.3 (5-101) postoperatively. Half of the patients (n = 11) had poor lead positioning alone or in combination with other problems (combined with: other disease n = 6, functional dystonia n = 1, other problems n = 2). Other problems were disease other than isolated inherited or idiopathic dystonia (n = 5), fixed deformities (n = 2), functional dystonia (n = 3), and other causes (n = 1). Excluding patients with poor lead location from further analysis, non-isolated dystonia accounted for 45.5%, functional dystonia for 27.3%, and fixed deformities for 18.2%. In patients with true isolated dystonia, lead location was the most frequent problem. CONCLUSION: After exclusion of lead placement and stimulation programming issues, non-isolated dystonia, functional dystonia and fixed deformities account for the majority of GPi-DBS failures in dystonia.

Deep Brain Stimulation of the H Fields of Forel Alleviates Tics in Tourette Syndrome.

The current rationale for target selection in Tourette syndrome revolves around the notion of cortico-basal ganglia circuit involvement in the pathophysiology of the disease. However, despite extensive research, the ideal target for deep brain stimulation (DBS) is still under debate, with many structures being neglected and underexplored. Based on clinical observations and taking into account the prevailing hypotheses of network processing in Tourette syndrome, we chose the fields of Forel, namely field H1, as a target for DBS. The fields of Forel constitute the main link between the striatopallidal system and the thalamocortical network, relaying pallidothalamic projections from core anatomical structures to the thalamic ventral nuclear group. In a retrospective study we investigated two patients suffering from chronic, medically intractable Tourette syndrome who underwent bilateral lead implantation in field H1 of Forel. Clinical scales revealed significant alleviation of tics and comorbid symptoms, namely depression and anxiety, in the postoperative course in both patients.

Micro-Multileaf Collimator LINAC Radiosurgery for Vestibular Schwannomas.

OBJECTIVE: This study evaluates the efficacy of linear accelerator (LINAC) radiosurgery using micro multi-leaf collimator technique (µMLC) in the treatment of a consecutive series of patients with vestibular schwannomas. PATIENTS AND METHODS: In this retrospective study, we enrolled 50 patients with non-neurofibromatosis type 2 vestibular schwannoma who were treated with µMLC LINAC-based SRS at University Hospital of Cologne, Germany. A minimum clinical follow-up of 24 months was conducted. Thirty-nine out of the 50 tumors (78 %) were treated with µMLC LINAC as a primary treatment (a newly diagnosed tumor). The remaining 11 vestibular schwannomas (22%) were treated as a salvage treatment (5 patients with a residual tumor; and 6 patients with a recurrent tumor following a microsurgical resection). The median tumor volume was 1.4 ml. The median tumor surface dose, median maximal dose and median therapeutic isodose were 12 Gy, 16 Gy and 77% respectively. RESULTS: Follow-up MR images showed that a tumor progression-free status was achieved for 95.7% of patients. Partial tumor shrinkage was observed after µMLC LINAC SRS for 21.3% of patients. No change in tumor size (a stable tumor) was noted for 74.5% of patients. Tumor progression was observed for 4.3% of patients. At the end of follow-up, the actuarial 5- year and 10 year progression-free survival after radiosurgery were both 95.7%. CONCLUSIONS: LINAC radiosurgery using a micro multi-leaf collimator for vestibular schwannomas smaller than 3 cm is effective in yielding a high local tumor control, whereas the treatment-related morbidity remains low.

Intensity-based 2D 3D registration for lead localization in robot guided deep brain stimulation.

Intraoperative assessment of lead localization has become a standard procedure during deep brain stimulation surgery in many centers, allowing immediate verification of targeting accuracy and, if necessary, adjustment of the trajectory. The most suitable imaging modality to determine lead positioning, however, remains controversially discussed. Current approaches entail the implementation of computed tomography and magnetic resonance imaging. In the present study, we adopted the technique of intensity-based 2D 3D registration that is commonly employed in stereotactic radiotherapy and spinal surgery. For this purpose, intraoperatively acquired 2D x-ray images were fused with preoperative 3D computed tomography (CT) data to verify lead placement during stereotactic robot assisted surgery. Accuracy of lead localization determined from 2D 3D registration was compared to conventional 3D 3D registration in a subsequent patient study. The mean Euclidian distance of lead coordinates estimated from intensity-based 2D 3D registration versus flat-panel detector CT 3D 3D registration was 0.7 mm ± 0.2 mm. Maximum values of these distances amounted to 1.2 mm. To further investigate 2D 3D registration a simulation study was conducted, challenging two observers to visually assess artificially generated 2D 3D registration errors. 95% of deviation simulations, which were visually assessed as sufficient, had a registration error below 0.7 mm. In conclusion, 2D 3D intensity-based registration revealed high accuracy and reliability during robot guided stereotactic neurosurgery and holds great potential as a low dose, cost effective means for intraoperative lead localization.

Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series.

BACKGROUND: The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. METHODS: In this retrospective trial, four patients (three female, one male) aged 31-48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. RESULTS: Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed "partial response" on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46% in the de novo group; anxiety symptoms improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. CONCLUSION: MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders.

Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children.

PURPOSE: Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. PATIENTS AND METHODS: Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9-196.6 months). RESULTS: Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. CONCLUSION: Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations.

Motor Improvement and Emotional Stabilization in Patients With Tourette Syndrome After Deep Brain Stimulation of the Ventral Anterior and Ventrolateral Motor Part of the Thalamus.

BACKGROUND: Since its first application in 1999, the potential benefit of deep brain stimulation (DBS) in reducing symptoms of otherwise treatment-refractory Tourette syndrome (TS) has been documented in several publications. However, uncertainty regarding the ideal neural targets remains, and the eventuality of so far undocumented but possible negative long-term effects on personality fuels the debate about the ethical implications of DBS. METHODS: In this prospective open-label trial, eight patients (three female, five male) 19-56 years old with severe and medically intractable TS were treated with high-frequency DBS of the ventral anterior and ventrolateral motor part of the thalamus. To assess the course of TS, its clinical comorbidities, personality parameters, and self-perceived quality of life, patients underwent repeated psychiatric assessments at baseline and 6 and 12 months after DBS onset. RESULTS: Analysis indicated a strongly significant and beneficial effect of DBS on TS symptoms, trait anxiety, quality of life, and global functioning with an apparently low side-effect profile. In addition, presurgical compulsivity, anxiety, emotional dysregulation, and inhibition appeared to be significant predictors of surgery outcome. CONCLUSIONS: Trading off motor effects and desirable side effects against surgery-related risks and negative implications, stimulation of the ventral anterior and ventrolateral motor part of the thalamus seems to be a valuable option when considering DBS for TS.