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.

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.

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.

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.

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.

Stereotactic interstitial brachytherapy for the treatment of oligodendroglial brain tumors.

PURPOSE: We evaluated the treatment of oligodendroglial brain tumors with interstitial brachytherapy (IBT) using (125)iodine seeds ((125)I) and analyzed prognostic factors. PATIENTS AND METHODS: Between January 1991 and December 2010, 63 patients (median age 43.3 years, range 20.8-63.4 years) suffering from oligodendroglial brain tumors were treated with (125)I IBT either as primary, adjuvantly after incomplete resection, or as salvage therapy after tumor recurrence. Possible prognostic factors influencing disease progression and survival were retrospectively investigated. RESULTS: The actuarial 2-, 5-, and 10-year overall and progression-free survival rates after IBT for WHO II tumors were 96.9, 96.9, 89.8 % and 96.9, 93.8, 47.3 %; for WHO III tumors 90.3, 77, 54.9 % and 80.6, 58.4, 45.9 %, respectively. Magnetic resonance imaging demonstrated complete remission in 2 patients, partial remission in 13 patients, stable disease in 17 patients and tumor progression in 31 patients. Median time to progression for WHO II tumors was 87.6 months and for WHO III tumors 27.8 months. Neurological status improved in 10 patients and remained stable in 20 patients, while 9 patients deteriorated. There was no treatment-related mortality. Treatment-related morbidity was transient in 11 patients. WHO II, KPS ≥ 90 %, frontal location, and tumor surface dose > 50 Gy were associated with increased overall survival (p ≤ 0.05). Oligodendroglioma and frontal location were associated with a prolonged progression-free survival (p ≤ 0.05). CONCLUSION: Our study indicates that IBT achieves local control rates comparable to surgery and radio-/chemotherapy treatment, is minimally invasive, and safe. Due to the low rate of side effects, IBT may represent an attractive option as part of a multimodal treatment schedule, being supplementary to microsurgery or as a salvage therapy after chemotherapy and conventional irradiation.

Stereotactic LINAC radiosurgery for the treatment of typical intracranial meningiomas. Efficacy and safety after a follow-up of over 12 years.

PURPOSE: The efficacy and safety of stereotactic radiosurgery (SRS) for treatment of intracranial meningiomas has been demonstrated in numerous studies with short- and intermediate-term follow-up. In this retrospective single-center study, we present long-term outcomes of SRS performed with a linear accelerator (LINAC) for typical intracranial meningiomas. PATIENTS AND METHODS: Between August 1990 and December 2007, 148 patients with 168 typical intracranial meningiomas were treated with stereotactic LINAC-SRS, either as primary treatment or after microsurgical resection. A median tumor surface dose of 12 Gy (range 7-20 Gy) and a median maximum dose of 24.1 Gy (range 11.3-58.6 Gy) was applied. The median target volume was 4.7 ml (range 0.2-32.8 ml, SD ± 4.8 ml). RESULTS: Overall mean radiological follow-up was 12.6 years. Tumor shrinkage was seen in 75 (44.6 %) and stable disease in 85 (50.6 %) cases. Eight of 168 meningiomas (4.8 %) showed local tumor progression. The tumor control rate (TCR) after 5, 10, and 15 years was 93.6 % at each time point, and the progression-free survival (PSF) rates were 92, 89, and 89 %, respectively. The neurological symptoms existing prior to LINAC-SRS improved in 77 patients (59.7 %), remained unchanged in 42 (32.6 %), and deteriorated in 10 (7.8 %) patients. CONCLUSION: Our study emphasizes the efficacy of LINAC-SRS for de novo, residual and recurrent typical intracranial meningiomas. A high long-term local TCR with a low morbidity rate could be achieved. LINAC-SRS should thus be considered as a primary treatment option, as one arm of a combined treatment approach for incompletely resected meningiomas, or as a salvage therapy for recurrences.

Stereotactic LINAC-Radiosurgery for Glomus Jugulare Tumors: A Long-Term Follow-Up of 27 Patients.

BACKGROUND: The optimal treatment of glomus jugulare tumors (GJTs) remains controversial. Due to the critical location, microsurgery still provides high treatment-related morbidity and a decreased quality of life. Thus, we performed stereotactical radiosurgery (SRS) for the treatment of GJTs and evaluated the long-term outcome. METHODS: Between 1991 and 2011, 32 patients with GJTs underwent SRS using a linear accelerator (LINAC) either as primary or salvage therapy. Twenty-seven patients (median age 59.9 years, range 28.7-79.9 years) with a follow-up greater than five years (median 11 years, range 5.3-22.1 years) were selected for retrospective analysis. The median therapeutic single dose applied to the tumor surface was 15 Gy (range 11-20 Gy) and the median tumor volume was 9.5 ml (range 2.8-51 ml). RESULTS: Following LINAC-SRS, 10 of 27 patients showed a significant improvement of their previous neurological complaints, whereas 12 patients remained unchanged. Five patients died during follow-up due to old age or other, not treatment-related reasons. MR-imaging showed a partial remission in 12 and a stable disease in 15 patients. No tumor progression was observed. The actuarial overall survival rates after five, ten and 20 years were 100%, 95.2% and 79.4%, respectively. CONCLUSIONS: Stereotactic LINAC-Radiosurgery can achieve an excellent long-term tumor control beside a low rate of morbidity in the treatment of GJTs. It should be considered as an alternative therapy regime to surgical resection or fractionated external beam radiation either as primary, adjuvant or salvage therapy.

Deep brain stimulation in the ventrolateral thalamus/subthalamic area in dystonia with head tremor.

BACKGROUND: Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design. METHODS: Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed. RESULTS: Th-DBS improved dystonic tremor and dystonia (P < 0.05; 57.1% and 70.4%, respectively). Head tremor amplitude and pain were also improved (P < 0.05; 77.5% and 90.0%, respectively). Side effects included dysarthria, gait disturbance, slowness of movement, and weight gain. CONCLUSION: Dystonic head tremor and dystonia can be improved with Th-DBS.

Intracranial ganglioglioma WHO I: results in a series of eight patients treated with stereotactic interstitial brachytherapy.

In this retrospective study we evaluated the efficacy of interstitial brachytherapy (IBT) using (125)Iodine seeds ((125)I) for intracranial ganglioglioma WHO I. Between October 1994 and March 2010, eight patients (m/f = 5/3, median age 30.4 years, age range 7-42.5 years) with intracranial ganglioglioma WHO I were treated with IBT using stereotactically implanted (125)I seeds. The median follow-up time was 41.5 months (range 16.7-140.1 months). Prior to interstitial brachytherapy one patient underwent microsurgical resection for three times; seven patients were treated with IBT primarily. In all patients we implanted the (125)I seeds stereotactically guided. The cumulative tumor surface dose ranged between 50 and 65 Gy (permanent implantation) and the median tumor volume was 5.6 ml (range 0.9-26 ml). After brachytherapy, follow-up MR imaging revealed complete remission in one patient, partial remission in three and stable disease in the remaining four patients. Five of eight patients presented with seizures were either seizure-free (1/5) or improved (4/5). Temporary treatment-related morbidity occurred in one patient only (headache, nausea/vomiting) and resolved completely under steroid medication after 4 weeks. No treatment-related mortality was observed. This study indicates that interstitial brachytherapy for the treatment of intracranial ganglioglioma WHO I is safe and provides a high rate of local tumor control. Due to the limited number of cases, it is not possible to conduct a rigorous statistical evaluation. Thus, larger numbers of patients are required.

Tractography-guided stimulation of somatosensory fibers for thalamic pain relief.

BACKGROUND: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. OBJECTIVES: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. METHODS: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. RESULTS: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. CONCLUSIONS: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.

Pitfalls and fallacies interfering with correct identification of embryonic stem cells implanted into the brain after experimental traumatic injury.

Cell-therapy was proposed to be a promising tool in case of death or impairment of specific cell types. Correct identification of implanted cells became crucial when evaluating the success of transplantation therapy. Various methods of cell labeling have been employed in previously published studies. The use of intrinsic signaling of green fluorescent protein (GFP) has led to a well known controversy in the field of cardiovascular research. We encountered similar methodological pitfalls after transplantation of GFP-transfected embryonic stem cells into rat brains following traumatic brain injury (TBI). As the identification of implanted graft by intrinsic autofluorescence failed, anti-GFP labeling coupled to fluorescent and conventional antibodies was needed to visualize the implanted cells. Furthermore, different cell types with strong intrinsic autofluorescence were found at the sites of injury and transplantation, thus mimicking the implanted stem cells. GFP-positive stem cells were correctly localized, using advanced histological techniques. The activation of microglia/macrophages, accompanying the transplantation post TBI, was shown to be a significant source of artefacts, interfering with correct identification of implanted stem cells. Dependent on the strategy of stem cell tracking, the phagocytosis of implanted cells as observed in this study, might also impede the interpretation of results. Critical appraisal of previously published data as well as a review of different histological techniques provide tools for a more accurate identification of transplanted stem cells.

Occurrence and recurrence of spontaneous chronic subdural haematoma is associated with a factor XIII deficiency.

OBJECTIVE: In some patients, chronic subdural haematoma (cSDH) appears to occur spontaneously with frequent re-bleeding events. The pathophysiology of this phenomenon is still poorly understood. Because coagulation factor XIII (FXIII) is known to be involved in vascular integrity, endothelial barrier function and wound healing, we evaluated the role of FXIII in spontaneous cSDH. METHODS: We prospectively scrutinised the origin of cSDH in 117 patients and identified a subgroup of patients suffering from spontaneous cSDH who were included in this study. We analysed the plasma activity of FXIII and standard coagulation parameters and compared these data to age- and sex-matched healthy controls. We assessed the occurrence of re-bleeding events using clinical and imaging data and compared FXIII activity in patients with and without re-bleeding events. RESULTS: Out of 117 cSDH patients, 18 individuals suffered from spontaneous cSDH in this study. The patients with spontaneous cSDH showed significantly lower FXIII activity than the control group (65% [52.75, 80.25] (median [IQR]) vs. 93% [81, 111], P=0.001), whereas standard coagulation parameters did not differ significantly between the groups. Six patients developed re-bleeding events after haematoma evacuation, and these patients expressed significantly lower FXIII activity compared to the other 12 patients (47.5% [33.5, 64] vs. 78.5% [58, 87], P=0.005). The patient group with FXIII≤68.5% differed significantly from the group with FXIII>68.5% when categorised by the occurrence of re-bleeding events (n=6/9 vs. n=0/9, P=0.009). This cut-off value predicted the re-bleeding events with a sensitivity of 100% and a specificity of 75% (positive predictive value: 66%, negative predictive value: 100%). CONCLUSION: FXIII deficiency may play a pathophysiological role in spontaneous cSDH, so we suggest investigating FXIII activity because it may predict re-bleeding events after treatment. In individuals with considerably low FXIII activity, FXIII substitution may mitigate the chronic nature of this disease.

Intracranial ependymoma: long-term results in a series of 21 patients treated with stereotactic (125)iodine brachytherapy.

BACKGROUND: We evaluated the long-term outcome in patients harboring intracranial ependymomas treated with interstitial brachytherapy (IBT). METHODS: Twenty-one patients (M/F = 9/12; median age: 29 years; range: 8-70 years), diagnosed with intracranial ependymoma (1 WHO I, 11 WHO II, 9 WHO III) were treated with IBT using stereotactically implanted (125)Iodine seeds between 1987 and 2010, either primarily, as adjuvant therapy following incomplete resection, or as salvage treatment upon tumor recurrence. Sixteen of 21 patients underwent microsurgical resection prior to IBT; in 5 patients, IBT was performed primarily after stereotactic biopsy for histological diagnosis. The cumulative tumor surface dose ranged from 50-65 Gy treating a median tumor volume of 3.6 ml (range, 0.3-11.6 ml). A median follow-up period of 105.3 months (range, 12.7-286.2 months) was evaluated. RESULTS: Actuarial 2-, 5- and 10-years overall- and disease-specific survival rates after IBT were each 90% and 100% at all times for ependymomas WHO I/II, for anaplastic ependymomas WHO III 100%, 100%, 70% and 100%, 100%, 86%, respectively. The neurological status of seven patients improved, while there was no change in 12 and deterioration in 2 patients, respectively. Follow-up MR images disclosed a complete tumor remission in 3, a partial remission in 12 and a stable disease in 6 patients. Treatment-associated morbidity only occurred in a single patient. CONCLUSIONS: This study shows that stereotactic IBT for intracranial ependymomas is safe and can provide a high degree of local tumor control. Due to the low rate of side effects, IBT may evolve into an attractive alternative to microsurgery in ependymomas located in eloquent areas or as a salvage treatment.