Cognition in epilepsy patients with hypothalamic hamartomas.

Many patients with epilepsy caused by hypothalamic hamartomas (HHs) have cognitive impairments during the course of the disease or following neurosurgical treatment. The purpose of this study was to assess cognitive function in these patients, as well as factors influencing preoperative cognitive performance and cognitive outcome after neurosurgical treatment. Using the two largest and most detailed neuropsychology datasets on HH and epilepsy from two centers, we retrospectively report on cognitive functions in 48 patients with structural epilepsy due to HH (mean age ± standard deviation [SD] 20 ± 12 years, range 5-53 years, median 16 years; disease duration mean 17 ± 11 years). Intelligence, verbal learning and recall, and speed and executive functions (processing speed and cognitive flexibility) were assessed before and on average 19 (±11) months after surgery (interstitial radiosurgery: N = 22; neurosurgical resection/disconnection: N = 26). Prior to neurosurgical treatment, 52% of patients showed impaired executive and 62% showed reduced verbal memory functions. A trend for a detrimental effect of higher drug load on cognitive functioning was found. After neurosurgical treatment, intellectual functions for the entire cohort tended to increase. This correlated with improved seizure frequency and decreased number of antiepileptic drugs (AEDs). However, postoperative outcomes for individual patients were highly variable, with significant deteriorations in 17% (processing speed) to 34% (cognitive flexibility and verbal learning), and performance increases in 17% (intellectual functioning) up to 39% (processing speed) of the patients. Higher levels of presurgical performance were significant predictors of cognitive decline after surgery. These results are highly relevant for patient consultation and may help with therapeutic decisions.

Reduced glucose metabolism in neocortical network nodes remote from hypothalamic hamartomas reflects cognitive impairment.

The clinical appearance of patients with hypothalamic hamartomas is very heterogeneous, and interindividual variability of intellectual abilities is not completely understood. We retrospectively investigated cerebral dysfunction as indicated by reduced regional glucose metabolism in 29 patients (age range 7-49 years) with epilepsy due to hypothalamic hamartomas. Brain metabolism assessed by [18 F]FDG-PET was compared between patients with and without cognitive impairment controlled for unevenly distributed hamartoma lateralization seen on magnetic resonance imaging (MRI). Due to the broad age range, the variable "age" was included in the imaging analyses as a covariate. Additional voxel-wise analysis with hamartoma volume, disease duration, seizure severity, seizure frequency, and antiepileptic drug (AED) load as well as dosage and gender as further covariates was accomplished. Furthermore, global visual ratings on laterality of hypometabolism patterns were assessed according to clinical standards and related to hamartoma lateralization on MRI as well as lateralization of electroencephalography (EEG) abnormalities. Cognitively impaired patients showed significantly reduced glucose metabolism in bilateral frontal as well as right parietal and posterior midline cortices (p < 0.005), irrespective of hamartoma lateralization seen on MRI. Additional voxel-wise analysis with the above-mentioned further covariates revealed comparable results. FDG uptake values within the main right frontal cluster obtained from group comparison were not associated with hamartoma volume, disease duration, or AED load. Irrespective of cognitive functioning, lateralization of reduced FDG uptake in global visual ratings was associated with lateralization of hypothalamic hamartomas seen on MRI (p < 0.01), but not with EEG abnormalities. We found regions of reduced glucose metabolism in cognitively impaired patients remote from the hypothalamic hamartomas in frontal and parietal regions, which have been identified as important network nodes in the human brain and are linked to higher cognitive functions.

MR evaluation of vessel size imaging of human gliomas: Validation by histopathology.

PURPOSE: To compare the vessel size and the cerebral blood volume in human gliomas with histopathology. Vessel size imaging (VSI) is a dynamic susceptibility contrast method for the assessment of the vessel size in normal and pathological tissue. Previous publications in rodents showed a satisfactory conformity with the vessel size derived from histopathology. To assess the clinical value, further, the progression-free interval was determined and correlated. MATERIALS AND METHODS: Twenty-five gliomas (WHO grade °II [n = 10], °III [n = 3], °IV [n = 12]) were prospectively included and received a stereotaxic biopsy after VSI. The vessel size and the cerebral blood volume (CBV) were calculated in regions of interest at the tumor edge and correlated with the vessel size measured by histopathology. RESULTS: Both VSI and CBV showed a good correlation with the vessel size in histopathology (up to r = 0.84, P < 0.001, and r = 0.62, P < 0.001, respectively). Slope and offset of the linear regression (y = 0.77x + 0.36 µm) suggest that the size of normal capillaries is overestimated with VSI, while for grossly enlarged vessels an underestimation occurs. Both VSI and CBV were negatively correlated with the progression-free interval (r = -0.57, P = 0.008, and r = -0.50, P = 0.025, respectively). CONCLUSION: The correlation between VSI and vessel size from histopathology is in good accordance with the animal studies. The overestimation of small capillary sizes is also known from the animal trials. Vessel size and CBV showed similar results, both for the correlation with the histopathological vessel size and the progression-free interval.

Retrospective analysis of 104 histologically proven adult brainstem gliomas: clinical symptoms, therapeutic approaches and prognostic factors.

BACKGROUND: Adult brainstem gliomas are rare primary brain tumors (<2% of gliomas). The goal of this study was to analyze clinical, prognostic and therapeutic factors in a large series of histologically proven brainstem gliomas. METHODS: Between 1997 and 2007, 104 patients with a histologically proven brainstem glioma were retrospectively analyzed. Data about clinical course of disease, neuropathological findings and therapeutic approaches were analyzed. RESULTS: The median age at diagnosis was 41 years (range 18-89 years), median KPS before any operative procedure was 80 (range 20-100) and median survival for the whole cohort was 18.8 months. Histopathological examinations revealed 16 grade I, 31 grade II, 42 grade III and 14 grade IV gliomas. Grading was not possible in 1 patient. Therapeutic concepts differed according to the histopathology of the disease. Median overall survival for grade II tumors was 26.4 months, for grade III tumors 12.9 months and for grade IV tumors 9.8 months. On multivariate analysis the relative risk to die increased with a KPS ≤ 70 by factor 6.7, with grade III/IV gliomas by the factor 1.8 and for age ≥ 40 by the factor 1.7. External beam radiation reduced the risk to die by factor 0.4. CONCLUSION: Adult brainstem gliomas present with a wide variety of neurological symptoms and postoperative radiation remains the cornerstone of therapy with no proven benefit of adding chemotherapy. Low KPS, age ≥ 40 and higher tumor grade have a negative impact on overall survival.

Memory outcome one year after stereotactic interstitial radiosurgery in patients with epilepsy due to hypothalamic hamartomas.

Epileptic seizures caused by hypothalamic hamartomas (HHs) are highly pharmacoresistant. Resective surgical approaches have shown some efficacy in controlling seizures; however, they bear a significant risk of postoperative mnemonic deterioration due to the close anatomical proximity of the HHs to structures essential for memory functions. We report on cognitive outcome in 26 patients with structural epilepsy due to HHs one year after interstitial radiosurgery. Individually, deteriorations occurred more frequently in declarative memory functions (in 20 to 50% of the patients), whereas more than 80% of the patients revealed stable or even improved performance in attentional functions. Preoperative better memory functions were associated with higher risk of postoperative performance decline. After radiosurgery, half of the patients showed more than 50%, and some up to 90%, of seizure reduction. Hypothalamic hamartoma volumes were significantly reduced at follow-up. Transient radiogenic edema found in 10/26 patients was not associated with further cognitive decline after radiosurgery. These results are highly relevant for therapeutic decisions and patient consultation on timing and choice of nonmedical treatment options for HHs.

Interstitial radiosurgery with iodine-125 seeds in the treatment of brain metastases, glial tumours and benign intracranial lesions.

In a retrospective single-centre study, we analysed data of 1,378 patients (55 % male, 45 % female) who underwent interstitial radiotherapy with 1,596 implanted Iodine-125 seeds in the Department of Stereotactic and Functional Neurosurgery in Freiburg from January 1990 to December 2011. The medical prerequisites and physical parameters of the treatment with Iodine-125 seeds are given. The method used in Freiburg relying on temporary Iodine-125 seed implants is described in detail and analysed. The survival rates and the peri-operative risk are evaluated. We conclude that interstitial radiosurgery with Iodine-125 seeds is a safe and useful tool, offering a wide range of treatment options for benign and also malignant intracranial lesions, especially if they are small, deep-seated, in eloquent areas, or not suitable for micro-surgery.

Impact of automated hotspot detection for (18)FET PET-guided stereotactic biopsy.

OBJECTIVE: The aim of this study was to explore the impact of automated hotspot detection on surgical planning of (18)FET PET-guided stereotactic serial biopsy. METHOD: Imaging of ten patients with brain lesions detected by MRI and showing increased (18)FET uptake on PET who were retrospectively and randomly assigned to compose the study. Stereotactic biopsy plans (PET-guided and MR-guided) were performed by two neurosurgeons for each patient, independently and blinded. For PET-guided plans, biopsy target was achieved by means of an automated hotspot detection system. MR-guided plans targeted contrast enhancement areas or hyperintense areas in T2-weighted sequences. FET uptake ratio (UR) was determined in the biopsy trajectory across the lesion. Highest UR (HUR) from both planning techniques was compared. RESULTS: Each single HUR obtained through PET-guided technique was higher than correspondent values from MR-guided technique. Mean HUR of 2.41 (SE ± 0.23) for PET-guided plans and 1.85 (±0.16) for MR-guided plans were respectively obtained. This difference was statistically significant (p = 0.002). CONCLUSION: The use of an automated hotspot detection system was able to provide higher FET HUR along stereotactic biopsy trajectories in comparison to those from MR-guided plans. The use of specially designed computational tools may refine surgical planning by improving biopsy targeting.

Cerebral Abscess Caused by Listeria monocytogenes: Case Report and Literature Review.

BACKGROUND: Listeria monocytogenes is an opportunistic gram-positive, facultative intracellular bacterium that causes invasive diseases mostly in pregnant women and immunosuppressed patients. Despite the predilection toward the central nervous system (CNS), it usually causes meningitis and meningoencephalitis, whereas brain abscesses are very uncommon. CASE PRESENTATION: We describe the case of a 69-year-old homeless patient with a brain abscess due to L. monocytogenes who was successfully treated surgically by a guided stereotactic aspiration and antibiotic therapy with ampicillin and gentamicin. Our patient was discharged after 4 weeks of therapy without neurologic deficits. Additionally, we provide a review of the literature of brain abscesses caused by L. monocytogenes. CONCLUSIONS: This case highlights the need to drain cerebral abscesses and culture pus to correctly treat patients with antibiotics, especially given the high mortality rate of this infectious entity.

Superselective anterior temporal resection in mesial temporal lobe epilepsy.

We report the case of a patient with pharmacoresistant mesial temporal lobe epilepsy presenting psychomotor seizures with onset at early childhood. MRI showed a blurred internal structure of the right hippocampus and right mammillary body atrophy. Neuropsychological testing revealed deficits in selective attention and visual planning. Non-invasive recording was not sufficient to precisely detect the seizure onset zone. Invasive recording showed seizure onset in the temporo-polar neocortex, with spread to the amygdalum and hippocampus. A superselective resection of the temporal pole and amygdalum was performed with preservation of the hippocampus. Histology revealed the presence of focal cortical dysplasia (Palmini type Ib). Seizure frequency was reduced after surgery, and seizure freedom for two years was achieved with optimisation of the antiepileptic drug regime. Memory functions were preserved, and selective attention and visual planning improved following limited resection. This case suggests that, in selected cases, highly targeted resections with preservation of memory-relevant structures may be the best choice considering both seizure control and unimpaired cognitive functioning.

BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors.

BACKGROUND: The prognosis for patients with recurrent glioblastoma is still poor with a median survival between 3 and 6 months. Reports about the application of carmustine (BCNU), one of the standard chemotherapeutic drugs in the treatment of newly diagnosed glioblastoma, in the recurrent situation are rare. METHODS: We performed a retrospective analysis of 35 patients with recurrent or progressive glioblastoma treated with 80 mg/m2 BCNU on days 1 on 3 intravenously at our department for efficacy, toxicity and prognostic factors. Progression free survival and overall survival were estimated by the Kaplan-Meier method. The influence of age, Karnofsky performance status (KPS), tumor burden, pretreatment with temozolomide (TMZ), type of surgery for initial diagnosis and number of previous relapses on outcome was analyzed in a proportional hazards regression model. RESULTS: The median age of the group was 53 years, median KPS was 70. Median progression free survival was 11 weeks (95% confidence interval [CI]: 8-15), median overall survival 22 weeks (95% CI: 18-27). The rate of adverse events, especially hematological toxicity, is relatively high, and in 3 patients treatment had to be terminated due to adverse events (one pulmonary embolism, one pulmonary fibrosis, and one severe bone marrow suppression). No influence of age, KPS, tumor burden, pre-treatment with TMZ and number of previous relapses on outcome could be demonstrated, while gross total resection prior to recurrence showed a borderline statistically significant negative impact on PFS and OS. These data compare well with historical survival figures. However prospective randomized studies are needed to evaluate BCNU efficacy against newer drugs like bevacizumab or the intensified temozolomide regime (one week on/one week off). CONCLUSION: In summary, BCNU treatment appears to be a valuable therapeutic option for recurrent glioblastomas, where no other validated radio- and/or chemotherapy are available.

Semiologic aspects of epileptic seizures in 31 patients with hypothalamic hamartoma.

PURPOSE: Characterization of seizure semiology in patients with hypothalamic hamartoma (HH) based on video-electroencephalography (EEG) monitoring (VEM). METHODS: We retrospectively analyzed seizure semiology of 31 patients (20 male, mean age 23.5 years) who underwent VEM at the University Hospitals Freiburg or Heidelberg, Germany. Inclusion criteria were magnetic resonance evidence of an HH, no prior surgical or radiosurgical treatment, and at least two video-documented seizures. A total of 263 seizures were included (mean number of seizures/patient 8.5, range 2-10). To analyze age-dependent changes in seizure semiology, patients were grouped into "children" (3-11 years, n = 5), "adolescents" (12-17 years, n = 4), and "adults" (≥18 years, n = 22). RESULTS: According to patient history, gelastic seizures had occurred in all patients, in 74% as the initial seizure type at epilepsy onset. In VEM, epileptic laughter varied from facial grinning to intense contractions of the diaphragm and body shaking. Unilateral motor signs were seen ipsi- and contralaterally to the HH. Tonic seizures were frequent and did not depend on the state of vigilance. Children, in contrast to adults and adolescents, did not show secondarily generalized tonic-clonic seizures, the gelastic component was the dominating and initial semiologic element, and seizures were significantly shorter. CONCLUSION: Seizure semiology is highly variable and age dependent. This may reflect network modulations with different propagation of ictal activity and/or secondary epileptogenesis. Detailed knowledge about such changes may contribute to both earlier recognition of seizures during childhood and better assignment of seizure types to a hypothalamic origin.

Neurosurgical treatment strategies in childhood craniopharyngiomas: is less more?

OBJECTIVE: Craniopharyngiomas in children are typically present in combination with heterogeneous clinical and neuroradiological findings. It has remained highly challenging to choose the optimal treatment strategy with regard to local tumor control and clinical outcome. Here, we analyze different treatment methods and evaluate the results. METHODS: We performed a detailed retrospective evaluation of 32 children <18 years old treated for craniopharyngioma between 1990 and 2008 at the University Hospital Freiburg. Three patient groups could be identified: children treated with microsurgical resection (n=17), with stereotactic cyst drainage and radiotherapy (n=7), and with various combined approaches (n=8). RESULTS: Six of seven children treated with stereotactic cyst punction and radiation are still alive. All of them are in an age-appropriate neuropsychological condition. Two of seven patients in this group have tumor recurrences. Fourteen of the 17 children treated with microsurgical resection show tumor recurrences (p=0.02). Fifteen are alive, and ten out of 17 show an age-appropriate neuropsychological development. The 8.5 years freedom from progression differed from 24% in the resection group to 71% in the cohort treated with stereotactic cyst drainage and radiotherapy (p=0.05). In the third group treated with various approaches, three of eight patients were treated for cystic recurrence. The average follow-up is 5.5 years. CONCLUSIONS: Based on our nonrandomized retrospective monocentric analysis, patients treated with less invasive stereotactic and radiotherapeutical methods have a more favorable long-term clinical outcome compared to children treated with a more radical microsurgical approach. Due to the possible implications of these results, further prospective trials should be encouraged.

Bilateral Globus Pallidus Internus Deep Brain Stimulation in a Case of Progressive Dystonia in Mohr-Tranebjaerg Syndrome with Bilateral Cochlear Implants.

INTRODUCTION: A 28-year-old man presented with a history of sensorineural deafness since early childhood treated with bilateral cochlear implants (CIs). He showed signs of debilitating dystonia that had been present since puberty. Dystonic symptoms, especially a protrusion of the tongue and bilateral hand tremor, had not responded to botulinum toxin therapy. We diagnosed Mohr-Tranebjaerg syndrome (MTS). METHODS AND MATERIAL: Deep brain stimulation (DBS) of the bilateral globus pallidus internus was performed predominantly with stereotaxic computed tomography angiography guidance under general anesthesia. Electrophysiology was used to identify the target regions and to guide DBS electrode placement. RESULTS: In the immediate postoperative course and stimulation, the patient showed marked improvement of facial, extremity, and cervical dystonia. More than 2 years after implantation, his dystonic symptoms had dramatically improved by 82%. DISCUSSION: MTS is a rare genetic disorder leading to sensorineural deafness, dystonia, and other symptoms. The use of DBS for the dystonia in MTS was previously described but not in the presence of bilateral CIs. CONCLUSION: DBS in MTS may be a viable option to treat debilitating dystonic symptoms. We describe successful DBS surgery, despite the presence of bilateral CIs, and stimulation therapy over 2 years.

Simultaneous Frame-assisted Stereotactic Placement of Subdural Grid Electrodes and Intracerebral Depth Electrodes.

BACKGROUND AND STUDY AIMS: In complex cases of drug-resistant focal epilepsy, the precise localization of the epileptogenic zone requires simultaneous implantation of depth and subdural grid electrodes. This study describes a new simple frame-assisted method that facilitates the simultaneous placement of both types of intracranial electrodes. MATERIAL AND METHODS: Ten consecutive patients were evaluated and divided into two groups. Group A included patients with simultaneous frame-assisted placement of depth and subdural grid electrodes. In group B, depth electrodes were implanted stereotactically; grid electrodes were implanted in a separate surgery. RESULTS: The placement of the subdural grid was accurate as individually designed by the epileptologists in all five patients from group A. In group B, one patient showed a slight and another one a significant deviation of the subdural grid position postoperatively. The mean surgical time in group A was shorter (280±62 minutes) compared with the mean duration of the surgical procedures in group B (336±51 minutes). CONCLUSION: The frame-assisted placement of subdural grid electrodes facilitates the surgical procedure for invasive video-electroencephalography monitoring in complex cases of drug-resistant focal epilepsy in which a combination of depth electrodes and subdural grid electrodes is needed, by reducing the surgical time and guaranteeing highly accurate electrode localizations.

The stereotactic suboccipitaltranscerebellar approach to lesions of the brainstem and the cerebellum.

OBJECTIVE: The stereotactic suboccipital-transcerebellar approach is widely regarded as technically demanding requiring substantial modifications of the standard stereotactic methods thus often making a transfrontal approach preferable. In this comprehensive series we aim to present our experience with the stereotactic suboccipital-transcerebellar approach to lesions of the brainstem or cerebellum using two standard stereotactic systems. PATIENTS AND METHODS: In the period of 2000-2015 overall 80 patients (mean age 43.95 ±â€¯23.76 years) with lesions of the brainstem or cerebellum underwent stereotactic surgery for diagnostic or therapeutic purposes via a suboccipital approach. In 59 patients stereotactic surgery was performed using the Riechert-Mundinger Stereotactic Frame, the Leksell Stereotactic Frame was used in 21 patients. For both frames standard systems were used without modification. Retrospective analysis of intraoperative stereotactic technique, achievement of the predefined surgical objectives and perioperative complications was carried out. RESULTS: In this series, the stereotactic suboccipital-transcerebellar approach proved to be feasible with two standard stereotactic systems. Using either frame the predefined surgical objective was achieved in 90.0%. A verified neuropathological diagnosis was obtained in 89.6%. Minor transient perioperative complications occurred in 8.75%. There was no surgery-related permanent morbidity or mortality. CONCLUSION: In this comprehensive series the stereotactic suboccipital-transcerebellar approach using a standard stereotactic system proved to be a favorable stereotactic approach with a high diagnostic success rate and no surgery-related permanent morbidity.

Frame-based stereotactic neurosurgery in children under the age of seven: Freiburg University's experience from 99 consecutive cases.

INTRODUCTION: Stereotactic frame-based procedures proved to be precise, safe and are of widespread use among adult patients. Regarding pediatric patients few data is available, therefore the use of the stereotactic frame remains controversial in this population. This motivated us to report our experience in stereotactic procedures in the youngest patients and review the literature concerning this subject. METHODS: All frame-based procedures performed in patients younger than seven years in the University of Freiburg during the last 10 years were retrospectively analyzed and discussed under the light of the current literature. RESULTS: The studied population was composed of 72 patients under the age of seven (mean 3.4±2.1 years-old), in whom 99 stereotactic procedures were performed. Brain tumor was present in 60 patients, hydrocephalus in five, cystic lesions in three, intracranial abscess in three and epilepsy in one patient. Stereotactic surgery was performed in 36 cases for brachytherapy, in 29 for biopsy, in 20 cases for cyst puncture, in eight for stereotactically guided endoscopic ventriculostomy, in five for catheter placement and in one case for depth electrode insertion. The overall complication rate was 5%. There were three cases of pin penetration through the skull, one case of frame dislocation after extensive cyst drainage and two skull fractures. Neurologic deficit related to frame fixation was observed in none of the cases. In disagreement with other authors, no case of pin related infection, air embolism, hematoma or CSF leak was observed. CONCLUSION: Frame-based stereotactic neurosurgery is a safe technique also in the youngest patients. Rather than the simple use of torque-limiting devices training and experience in the manual adjustment of the stereotactic frame in children have been proven to be crucial factors that contribute to reducing pin related complications.

Correlation of (18)F-fluoroethyl tyrosine positron-emission tomography uptake values and histomorphological findings by stereotactic serial biopsy in newly diagnosed brain tumors using a refined software tool.

BACKGROUND: Magnetic resonance imaging (MRI) is the standard neuroimaging method to diagnose neoplastic brain lesions, as well as to perform stereotactic biopsy surgical planning. MRI has the advantage of providing structural anatomical details with high sensitivity, though histological specificity is limited. Although combining MRI with other imaging modalities, such as positron-emission tomography (PET), has proven to increment specificity, exact correlation between PET threshold uptake ratios (URs) and histological diagnosis and grading has not yet been described. OBJECTIVES: The aim of this study was to correlate exactly the histopathological criteria of the biopsy site to its PET uptake value with high spatial resolution (mm(3)), and to analyze the diagnostic value of PET using the amino acid O-(2-[(18)F]fluoroethyl)-l-tyrosine ((18)F-FET) PET in patients with newly diagnosed brain lesions in comparison to histological findings obtained from stereotactic serial biopsy. PATIENTS AND METHODS: A total of 23 adult patients with newly diagnosed brain tumors on MRI were enrolled in this study. Subsequently to diagnoses, all patients underwent a (18)F-FET PET-guided stereotactic biopsy, using an original newly developed software module, which is presented here. Conventional MRI, stereotactic computed tomography series, and (18)F-FET PET images were semiautomatically fused, and hot-spot detection was performed for target planning. UR was determined using the uptake value from the biopsy sites in relation to the contralateral frontal white matter. UR values ≥1.6 were considered positive for glioma. High-grade glioma (HGG) was suspected with URs ≥3.0, while low-grade glioma (LGG) was suspected with URs between 1.6 and 3.0. Stereotactic serial biopsies along the trajectory at multiple sites were performed in millimeter steps, and the FET URs for each site were correlated exactly with a panel of 27 different histopathological markers. Comparisons between FET URs along the biopsy trajectories and the histological diagnoses were made with Pearson product-moment correlation coefficients. Analysis of variance was performed to test for significant differences in maximum UR between different tumor grades. RESULTS: A total of 363 biopsy specimens were taken from 23 patients by stereotactic serial biopsies. Histological examination revealed eight patients (35%) with an LGG: one with a World Health Organization (WHO)-I lesion and seven with a WHO-II lesion. Thirteen (57%) patients revealed an HGG (two with a WHO-III and three with a WHO-IV tumor), and two patients (9%) showed a process that was neither HGG nor LGG (group X or no-grade group). The correlation matrix between histological findings and the UR revealed five strong correlations. Low cell density in tissue samples was found to have a significant negative correlation with the measured cortical uptake rate (r=-0.43, P=0.02), as well as moderate cell density (r=-0.48, P=0.02). Pathological patterns of proliferation (r=0.37, P=0.04), GFAP (r=0.37, P=0.04), and Olig2 (r=0.36, P=0.05) showed a significant positive correlation with cortical URs. Analysis of variance tests showed a significant difference between the LGG and the HGG groups (F=8.27, P<0.002), but no significant differences when differentiating between the X group and the HGG (P=0.2)/LGG (P=0.8) groups, nor between the no-grade group and the WHO-I group. CONCLUSION: (18)F-FET PET is a valuable tool, as it allows the differentiation of HGGs from LGGs. Its use is not limited to preoperative evaluation; it may also refine biopsy targeting and improve tumor delimitation for radiotherapy. Histology is still necessary, and remains the gold standard for definitive diagnosis of brain lesions.

Stereotactic planning software for human neurotransplantation: suitability in 22 surgical cases of Huntington's disease.

PURPOSE: Intrastriatal neural transplantation using multiple grafts is an experimental approach to the treatment of Huntington's disease (HD). Brain atrophy makes stereotactic plans in these patients a tedious procedure with a risk of suboptimal spatial distribution of the grafts in transplantation procedures. Here we present a self-developed software to optimize the surgical stereotactic planning for bilateral neurotransplantation procedures. It allows close to symmetrical distribution of the stereotactic coordinates in relation to the mid-commissural point (MCP), proposing automatically the planning coordinates for the first transplanted hemisphere and mirrored coordinates to be used in the contra-lateral hemisphere. METHODS: Twenty-two consecutive HD patients underwent bilateral stereotactic striatal transplantation. Two caudate nucleus and four putaminal tracks were planned bilaterally. For the second, contra-lateral transplantation, the coordinates were mirrored in order to determine contralateral targets and trajectories. Intra-individual comparison between software given coordinates and finally used coordinates was performed. RESULTS: No statistical significance was found comparing a) the differences between coordinates proposed by the software and the final coordinates and b) the distribution of the transplantation sites in relation to the midline for the right vs. left hemisphere. No intra- or postoperative transplantation-related adverse events occurred. CONCLUSIONS: The use of model-based and mirrored coordinates allowed optimal spatial distribution of the grafts. Minor changes were required comparing right to left coordinates giving proof-of principle. The initial use of the software suggests that it may be useful in experimental transplantation trials where neural cell grafts are to be implanted into predefined target sites in the human brain, whether unilateral or bilateral.

Interstitial brachytherapy with iodine-125 seeds for low grade brain stem gliomas in adults: diagnostic and therapeutic intervention in a one-step procedure.

PURPOSE: To report on iodine-125 (I125) interstitial irradiation in the treatment of low grade brain stem gliomas in adults. PATIENTS AND METHODS: Ten patients with well-circumscribed lesions of the brainstem and histological confirmation of low grade glioma treated with stereotactically implanted I-125 seed in our department between 1995 and 2012 were retrospectively analyzed. RESULTS: In 9 patients the lesion was treated with one I-125 seed and in one patient, 2 spatial separated lesions were implanted, therefore a total of 11 I-125 seeds were implanted. The mean volume of the 11 lesions was 2.76 ml (range: 0.5-7.2 ml), mean activity of the seeds was 6.23 mCi (range: 1.5-11.1 mCi), mean duration of irradiation was 28.5 days (range: 21-41 days) and mean effective dose rate was 9.16 cGy/h (range: 6.2-12 cGy/h). The 30 days perioperative morbidity and mortality rate was 0%. Median follow up was 72.5 month (range 5-168 months). Six of ten patients were free of progression until last follow up. CONCLUSION: In our experience at the University Clinic in Freiburg Germany, interstitial radiosurgery based on MRI is a safe and effective method to diagnose and treat low grade gliomas of the brain stem. Furthermore randomized studies are needed to confirm the therapeutic impact of this method in comparison to external beam radiation of brain stem gliomas.