Quantifying intra-tumoral genetic heterogeneity of glioblastoma toward precision medicine using MRI and a data-inclusive machine learning algorithm.

BACKGROUND AND OBJECTIVE: Glioblastoma (GBM) is one of the most aggressive and lethal human cancers. Intra-tumoral genetic heterogeneity poses a significant challenge for treatment. Biopsy is invasive, which motivates the development of non-invasive, MRI-based machine learning (ML) models to quantify intra-tumoral genetic heterogeneity for each patient. This capability holds great promise for enabling better therapeutic selection to improve patient outcome. METHODS: We proposed a novel Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) to predict regional genetic alteration status within each GBM tumor using MRI. WSO-SVM was applied to a unique dataset of 318 image-localized biopsies with spatially matched multiparametric MRI from 74 GBM patients. The model was trained to predict the regional genetic alteration of three GBM driver genes (EGFR, PDGFRA and PTEN) based on features extracted from the corresponding region of five MRI contrast images. For comparison, a variety of existing ML algorithms were also applied. Classification accuracy of each gene were compared between the different algorithms. The SHapley Additive exPlanations (SHAP) method was further applied to compute contribution scores of different contrast images. Finally, the trained WSO-SVM was used to generate prediction maps within the tumoral area of each patient to help visualize the intra-tumoral genetic heterogeneity. RESULTS: WSO-SVM achieved 0.80 accuracy, 0.79 sensitivity, and 0.81 specificity for classifying EGFR; 0.71 accuracy, 0.70 sensitivity, and 0.72 specificity for classifying PDGFRA; 0.80 accuracy, 0.78 sensitivity, and 0.83 specificity for classifying PTEN; these results significantly outperformed the existing ML algorithms. Using SHAP, we found that the relative contributions of the five contrast images differ between genes, which are consistent with findings in the literature. The prediction maps revealed extensive intra-tumoral region-to-region heterogeneity within each individual tumor in terms of the alteration status of the three genes. CONCLUSIONS: This study demonstrated the feasibility of using MRI and WSO-SVM to enable non-invasive prediction of intra-tumoral regional genetic alteration for each GBM patient, which can inform future adaptive therapies for individualized oncology.

Image-localized biopsy mapping of brain tumor heterogeneity: A single-center study protocol.

Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease. Biopsies are required to obtain a pathological diagnosis and are predominantly taken from the tumor core, which often has different traits to the surrounding invasive tumor that typically leads to recurrent disease. One approach to solving this issue is to characterize the spatial heterogeneity of molecular, genetic, and cellular features of glioma through the intraoperative collection of multiple image-localized biopsy samples paired with multi-parametric MRIs. We have adopted this approach and are currently actively enrolling patients for our 'Image-Based Mapping of Brain Tumors' study. Patients are eligible for this research study (IRB #16-002424) if they are 18 years or older and undergoing surgical intervention for a brain lesion. Once identified, candidate patients receive dynamic susceptibility contrast (DSC) perfusion MRI and diffusion tensor imaging (DTI), in addition to standard sequences (T1, T1Gd, T2, T2-FLAIR) at their presurgical scan. During surgery, sample anatomical locations are tracked using neuronavigation. The collected specimens from this research study are used to capture the intra-tumoral heterogeneity across brain tumors including quantification of genetic aberrations through whole-exome and RNA sequencing as well as other tissue analysis techniques. To date, these data (made available through a public portal) have been used to generate, test, and validate predictive regional maps of the spatial distribution of tumor cell density and/or treatment-related key genetic marker status to identify biopsy and/or treatment targets based on insight from the entire tumor makeup. This type of methodology, when delivered within clinically feasible time frames, has the potential to further inform medical decision-making by improving surgical intervention, radiation, and targeted drug therapy for patients with glioma.

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Image-based models of T-cell distribution identify a clinically meaningful response to a dendritic cell vaccine in patients with glioblastoma.

BACKGROUND: Glioblastoma is an extraordinarily heterogeneous tumor, yet the current treatment paradigm is a "one size fits all" approach. Hundreds of glioblastoma clinical trials have been deemed failures because they did not extend median survival, but these cohorts are comprised of patients with diverse tumors. Current methods of assessing treatment efficacy fail to fully account for this heterogeneity. METHODS: Using an image-based modeling approach, we predicted T-cell abundance from serial MRIs of patients enrolled in the dendritic cell (DC) vaccine clinical trial. T-cell predictions were quantified in both the contrast-enhancing and non-enhancing regions of the imageable tumor, and changes over time were assessed. RESULTS: A subset of patients in a DC vaccine clinical trial, who had previously gone undetected, were identified as treatment responsive and benefited from prolonged survival. A mere two months after initial vaccine administration, responsive patients had a decrease in model-predicted T-cells within the contrast-enhancing region, with a simultaneous increase in the T2/FLAIR region. CONCLUSIONS: In a field that has yet to see breakthrough therapies, these results highlight the value of machine learning in enhancing clinical trial assessment, improving our ability to prospectively prognosticate patient outcomes, and advancing the pursuit towards individualized medicine.

Clinical Outcomes of Stereotactic Radiosurgery-Related Radiation Necrosis in Patients with Intracranial Metastasis from Melanoma.

Background: Radiation necrosis (RN) is a clinically relevant complication of stereotactic radiosurgery (SRS) for intracranial metastasis (ICM) treatments. Radiation necrosis development is variable following SRS. It remains unclear if risk factors for and clinical outcomes following RN may be different for melanoma patients. We reviewed patients with ICM from metastatic melanoma to understand the potential impact of RN in this patient population. Methods: Patients who received SRS for ICM from melanoma at Mayo Clinic Arizona between 2013 and 2018 were retrospectively reviewed. Data collected included demographics, tumor characteristics, radiation parameters, prior surgical and systemic treatments, and patient outcomes. Radiation necrosis was diagnosed by clinical evaluation including brain magnetic resonance imaging (MRI) and, in some cases, tissue evaluation. Results: Radiation necrosis was diagnosed in 7 (27%) of 26 patients at 1.6 to 38 months following initial SRS. Almost 92% of all patients received systemic therapy and 35% had surgical resection prior to SRS. Patients with RN trended toward having larger ICM and a prior history of surgical resection, although statistical significance was not reached. Among patients with resection, those who developed RN had a longer period between surgery and SRS start (mean 44 vs 33 days). Clinical improvement following treatment for RN was noted in 2 (29%) patients. Conclusions: Radiation necrosis is relatively common following SRS for treatment of ICM from metastatic melanoma and clinical outcomes are poor. Further studies aimed at mitigating RN development and identifying novel approaches for treatment are warranted.

Subclinical seizures on stereotactic EEG: characteristics and prognostic value.

OBJECTIVE: Although stereotactic EEG (sEEG) has become a widely used intracranial EEG technique, the significance of subclinical seizures (SCS) recorded on sEEG is unclear and studies examining this finding on sEEG are limited. We investigated (1) the prevalence of SCS in patients undergoing sEEG and clinical factors associated with their presence, (2) how often the subclinical seizure onset zone (SOZ) colocalizes with clinical SOZ, (3) the association of SCS and surgical outcomes, and (4) the influence of resection of the subclinical SOZ on surgical outcome. METHODS: We reviewed all patients who underwent intracranial monitoring with sEEG at our institution from 2015 through 2020 (n=169). Patient and seizure characteristics were recorded, as was concordance of subclinical and clinical seizures and post-surgical outcomes. RESULTS: SCS were observed during sEEG monitoring in 84 of 169 patients (50%). There was no difference in the prevalence of SCS based on imaging abnormalities, temporal vs extratemporal SOZ, number of electrodes, or pathology. SCS were more common in females than males (62% vs 40%, p=0.0054). SCS had complete concordance with clinical SOZ in 40% of patients, partial concordance in 29%, overlapping in 19%, and discordant in 12%. Eighty-three patients had surgery, 44 of whom had SCS. There was no difference in excellent outcome (ILAE 12 or 2) based on the presence of SCS or SCS concordance with clinical SOZ; however, there were improved outcomes in patients with complete resection of the subclinical SOZ compared with patients with incomplete resection (p =0.013). SIGNIFICANCE: These findings demonstrate that SCS are common during sEEG and colocalize with the clinical SOZ in most patients. Discordance with clinical SOZ does not necessarily predict poor surgical outcome; rather, complete surgical treatment of the subclinical SOZ correlates with excellent outcome. For unclear reasons, subclinical seizures occurred more commonly in females than males.

Outcomes and Principles of Patient Selection for Laser Interstitial Thermal Therapy for Metastatic Brain Tumor Management: A Multisite Institutional Case Series.

BACKGROUND: Laser interstitial thermal therapy (LITT) is an emerging treatment modality for both primary brain tumors and metastases. We report initial outcomes after LITT for metastatic brain tumors across 3 sites at our institution and discuss potential strategies for optimal patient selection and outcomes. METHODS: International Classification of Diseases, Ninth Revision and Tenth Revision codes were used to identify patients with malignant brain tumors treated via LITT across all 3 Mayo Clinic sites with at least 6 months follow-up. Local control was based on radiologic and clinical evidence. Overall survival was measured from time of receiving LITT until death or end of the study period. RESULTS: Twenty-three patients were treated for progression of a single (n = 21) or multiple (n = 2) previously radiated metastatic lesions and/or radiation necrosis. Median age was 56 years (interquartile range, 47-66.5 years). LITT achieved local control of the lesion in most patients with metastatic tumors or radiation necrosis (n = 18; 81.8%) for the duration of follow-up. One patient did not have local control data available. Thirteen (56.5%) patients remained alive at the end of the study period. No other patients died of their treated disease during the study period; 5 of 10 deaths were attributable to central nervous system progression outside the treated lesion. Although median survival for this cohort has not yet been reached, the current median survival is 16 months (interquartile range, 12-48.5 months) after LITT for metastatic/radiation necrosis lesions. CONCLUSIONS: LITT was associated with sustained local control in 81.8% of patients treated for radiographic progression of metastatic central nervous system disease.

Microvascular Decompression Technique for Trigeminal Neuralgia Using a Vascular Clip.

Microvascular decompression (MVD) surgery is a well-established, effective treatment option for trigeminal neuralgia1 and hemifacial spasm.2 In 1967, Janetta et al3 introduced the concept of MVD surgery and pioneered the Janetta technique in which Teflon felt implants are placed between the trigeminal nerve and offending vessel. Though many cases are successfully managed with Teflon interposition, alternative techniques have been developed with the objective to alleviate vascular compression symptoms indefinitely, including transposition using biological glue,4 vascular clips,5,6 and a variety of "sling" techniques.7 In Video 1, we demonstrate a fenestrated clip transposition technique in the treatment of trigeminal neuralgia. We present the case of a 72-year-old female who presented with classic trigeminal neuralgia pain along the V2 and V3 distributions. Magnetic resonance imaging revealed evident compression of the trigeminal nerve by the superior cerebellar artery (SCA). A retrosigmoid craniotomy was performed, and the vascular loop of the SCA was visualized compressing the root entry zone with significant indentation of the trigeminal nerve. Wide arachnoid dissection along the SCA was carried out in order to mobilize the SCA away from the nerve. A small slit was created in the undersurface of the tentorium, and then the SCA loop was transposed to the tentorium using a fenestrated aneurysm clip. The postoperative course was uneventful, and the patient had complete resolution of her facial pain at 6-month follow-up. This method is likely an effective and durable method of decompression for trigeminal neuralgia.

Uncertainty quantification in the radiogenomics modeling of EGFR amplification in glioblastoma.

Radiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have directly addressed uncertainty in these model predictions. We developed a radiogenomics ML model to quantify uncertainty using transductive Gaussian Processes (GP) and a unique dataset of 95 image-localized biopsies with spatially matched MRI from 25 untreated Glioblastoma (GBM) patients. The model generated predictions for regional EGFR amplification status (a common and important target in GBM) to resolve the intratumoral genetic heterogeneity across each individual tumor-a key factor for future personalized therapeutic paradigms. The model used probability distributions for each sample prediction to quantify uncertainty, and used transductive learning to reduce the overall uncertainty. We compared predictive accuracy and uncertainty of the transductive learning GP model against a standard GP model using leave-one-patient-out cross validation. Additionally, we used a separate dataset containing 24 image-localized biopsies from 7 high-grade glioma patients to validate the model. Predictive uncertainty informed the likelihood of achieving an accurate sample prediction. When stratifying predictions based on uncertainty, we observed substantially higher performance in the group cohort (75% accuracy, n = 95) and amongst sample predictions with the lowest uncertainty (83% accuracy, n = 72) compared to predictions with higher uncertainty (48% accuracy, n = 23), due largely to data interpolation (rather than extrapolation). On the separate validation set, our model achieved 78% accuracy amongst the sample predictions with lowest uncertainty. We present a novel approach to quantify radiogenomics uncertainty to enhance model performance and clinical interpretability. This should help integrate more reliable radiogenomics models for improved medical decision-making.

Microvascular Transposition Without Teflon: A Single Institution's 17-Year Experience Treating Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) refractory to medical management is often treated with microvascular decompression (MVD) involving the intracranial placement of Teflon. The placement of Teflon is an effective treatment, but does apply distributed pressure to the nerve and has been associated with pain recurrence. OBJECTIVE: To report the rate of postoperative pain recurrence in TN patients who underwent MVD surgery using a transposition technique with fibrin glue without Teflon. METHODS: Patients were eligible for our study if they were diagnosed with TN, did not have multiple sclerosis, and had an offending vessel that was identified and transposed with fibrin glue at our institution. All eligible patients were given a follow-up survey. We used a Kaplan-Meier (KM) model to estimate overall pain recurrence. RESULTS: A total of 102 patients met inclusion criteria, of which 85 (83%) responded to our survey. Overall, 76 (89.4%) participants responded as having no pain recurrence. Approximately 1-yr pain-free KM estimates were 94.1% (n = 83), 5-yr pain-free KM estimates were 94.1% (n = 53), and 10-yr pain-free KM estimates were 83.0% (n = 23). CONCLUSION: Treatment for TN with an MVD transposition technique using fibrin glue may avoid some cases of pain recurrence. The percentage of patients in our cohort who remained pain free at a maximum of 17 yr follow-up is on the high end of pain-free rates reported by MVD studies using Teflon. These results indicate that a transposition technique that emphasizes removing any compression near the trigeminal nerve root provides long-term pain-free rates for patients with TN.

Does location matter? Characterisation of the anatomic locations, molecular profiles, and clinical features of gliomas.

BACKGROUND: Neuroanatomic locations of gliomas may influence clinical presentations, molecular profiles, and patients' prognoses. METHODS: We investigated our institutional cancer registry to include patients with glioma over a 10-year period. Statistical tests were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. Survival analysis methods were then used to assess associations between location and overall survival in the full cohort, as well as in relevant subgroups. RESULTS: 182 gliomas were identified. Of the tumours confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and seven occipital tumours (3.8%) identified. Tumours affecting the temporal lobe were associated with reduced overall survival when compared to all other tumours (11 months vs. 13 months, log-rank p = 0.0068). In subgroup analyses, this result was significant for males [HR (95%CI) 2.05 (1.30, 3.24), p = 0.002], but not for females [HR (95%CI) 1.12 (0.65, 1.93), p = 0.691]. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in six frontal, two temporal, one thalamic, and one multifocal tumour. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, nine of which were frontal lobe tumours. MGMT methylation was assessed in 45 cases; 7/14 frontal tumours and 6/13 temporal tumours were methylated. CONCLUSION: Our results support the hypothesis that the anatomical locations of gliomas influence patients' clinical courses. Temporal lobe tumours were associated with poorer survival, though this association appeared to be driven by these patients' more aggressive tumour profiles and higher risk baseline demographics. Independently, female patients who had temporal lobe tumours fared better than males. Molecular analysis was limited by the low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas. IMPORTANCE OF THIS STUDY: The specific neuroanatomic location of tumours in the brain is thought to be predictive of treatment options and overall prognosis. Despite evidence for the clinical significance of this information, there is relatively little information available regarding the incidence and prevalence of tumours in the different anatomical regions of the brain. This study has more fully characterised tumour prevalence in different regions of the brain. Additionally, we have analysed how this information may affect tumours' molecular characteristics, treatment options offered to patients, and patients' overall survival. This information will be informative both in the clinical setting and in directing future research.

Expanding the Spectrum of Radiation Necrosis After Stereotactic Radiosurgery (SRS) for Intracranial Metastases From Lung Cancer: A Retrospective Review.

OBJECTIVE: Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN. METHODS: We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes. RESULTS: Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality. CONCLUSIONS: This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.

Vascular Transposition of the Superior Cerebellar Artery Using a Fenestrated Clip and Fibrin Glue in Trigeminal Neuralgia: 2-Dimensional Operative Video.

This is the case of an 86-yr-old gentleman who presented with left facial pain exacerbated by eating, drinking, chewing, and shaving (distribution: V2, V3). The patient was diagnosed with trigeminal neuralgia and was refractory to medications. Imaging showed a superior cerebellar artery (SCA) loop adjacent to the trigeminal nerve root entry zone and a decision to perform a microvascular decompression of the fifth nerve was presented to the patient. After patient informed consent was obtained, a standard 3 cm × 3 cm retrosigmoid craniotomy was performed with the patient in a supine head turned position and in reverse Trendelenburg. The arachnoid bands tethering the SCA to the trigeminal nerve were sharply divided. A slit was then made in the tentorium and a 3 mm fenestrated clip was then used to secure the transposed SCA away from the trigeminal nerve. The SCA proximal to this was slightly patulous in its course so a small amount of a fibrin glue was also used to secure the more proximal SCA to the tentorium. The patient was symptom-free postoperatively and no longer required medical therapy. Additionally, imaging was consistent with adequate separation of the nerve from adjacent vessels.1-5.

Nervus intermedius and the surgical management of geniculate neuralgia.

OBJECTIVE: Geniculate neuralgia (GN) is an uncommon craniofacial pain syndrome attributable to nervus intermedius (NI) dysfunction. Diagnosis and treatment can be challenging, due to the complex nature of ear sensory innervation, resulting in clinical overlap with trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN). METHODS: A retrospective review of a prospective neurosurgical database at our institution was performed, 2000-2017, with a corresponding systematic literature review. Pain outcomes were dichotomized as unfavorable for unchanged/worsened symptoms versus favorable if improved/resolved. Eight formalin-fixed brains were examined to describe NI at the brainstem. RESULTS: Eleven patients were surgically treated for GN-9 primary, 2 reoperations. The median age was 48, 7 patients were female, and the median follow-up was 11 months (range 3-143). Seven had ≥ 2 probable cranial neuralgias. NI was sectioned in 9 and treated via microvascular decompression (MVD) in 2. Five patients underwent simultaneous treatment for TN (4 MVD; 1 rhizotomy) and 5 for GPN (3 MVD; 2 rhizotomy). Eleven reported symptomatic improvement (100%); 8 initially reported complete resolution (73%). Pain outcomes at last contact were favorable in 8 (73%)-all among the 9 primary operations (89% vs 0%, p = 0.054). Six prior series reported outcomes in 111 patients. CONCLUSIONS: GN is rare, and diagnosis is confounded by symptomatic overlap with TN/GPN. Directed treatment of all possible neuralgias improved pain control in almost all primary operations. Repeat surgery seems a risk factor for an unfavorable outcome. NI is adherent to superomedial VIII at the brainstem; the intermediate/cisternal portion is optimal for visualization and sectioning.

Laser ablation for mesial temporal epilepsy: a multi-site, single institutional series.

OBJECTIVEAlthough it is still early in its application, laser interstitial thermal therapy (LiTT) has increasingly been employed as a surgical option for patients with mesial temporal lobe epilepsy. This study aimed to describe mesial temporal lobe ablation volumes and seizure outcomes following LiTT across the Mayo Clinic's 3 epilepsy surgery centers.METHODSThis was a multi-site, single-institution, retrospective review of seizure outcomes and ablation volumes following LiTT for medically intractable mesial temporal lobe epilepsy between October 2011 and October 2015. Pre-ablation and post-ablation follow-up volumes of the hippocampus were measured using FreeSurfer, and the volume of ablated tissue was also measured on intraoperative MRI using a supervised spline-based edge detection algorithm. To determine seizure outcomes, results were compared between those patients who were seizure free and those who continued to experience seizures.RESULTSThere were 23 patients who underwent mesial temporal LiTT within the study period. Fifteen patients (65%) had left-sided procedures. The median follow-up was 34 months (range 12-70 months). The mean ablation volume was 6888 mm3. Median hippocampal ablation was 65%, with a median amygdala ablation of 43%. At last follow-up, 11 (48%) of these patients were seizure free. There was no correlation between ablation volume and seizure freedom (p = 0.69). There was also no correlation between percent ablation of the amygdala (p = 0.28) or hippocampus (p = 0.82) and seizure outcomes. Twelve patients underwent formal testing with computational visual fields. Visual field changes were seen in 67% of patients who underwent testing. Comparing the 5 patients with clinically noticeable visual field deficits to the rest of the cohort showed no significant difference in ablation volume between those patients with visual field deficits and those without (p = 0.94). There were 11 patients with follow-up neuropsychological testing. Within this group, verbal learning retention was 76% in the patients with left-sided procedures and 89% in those with right-sided procedures.CONCLUSIONSIn this study, there was no significant correlation between the ablation volume after LiTT and seizure outcomes. Visual field deficits were common in formally tested patients, much as in patients treated with open temporal lobectomy. Further studies are required to determine the role of amygdalohippocampal ablation.

Infection and Erosion Rates in Trials of a Cranially Implanted Neurostimulator Do Not Increase with Subsequent Neurostimulator Placements.

BACKGROUND/AIMS: The RNS® System utilizes a cranially implanted neurostimulator attached to leads placed at the seizure focus to provide brain responsive stimulation for the treatment of medically intractable partial onset epilepsy. Infection and erosion rates related to the cranial implant site were assessed overall and by neurostimulator procedure to determine whether rates increased with additional procedures. METHODS: Infection and erosion rates were calculated as (1) chance per neurostimulator procedure, (2) incidence per patient implant year, and (3) rates for initial and each subsequent neurostimulator implant (generalized estimating equation). RESULTS: In 256 patients followed for an average of 7 years, the infection rate was 3.7% per neurostimulator procedure (n = 31/840), and the rate of erosions was 0.8% per neurostimulator procedure (n = 7/840). Rates did not increase with subsequent neurostimulator procedures (p = 0.66, infection; p = 0.70, erosion). A prior infection or erosion at the implant site did not significantly increase the risk at a later procedure (p ≥ 0.05 for all combinations). CONCLUSION: These data indicate that the risk for infection compares favorably to other neurostimulation devices and suggest that rates of infection and erosion do not increase with subsequent neurostimulator replacements.

Hemicraniectomy for Ischemic and Hemorrhagic Stroke: Facts and Controversies.

Malignant large artery stroke is associated with high mortality of 70% to 80% with best medical management. Decompressive craniectomy (DC) is a highly effective tool in reducing mortality. Convincing evidence has accumulated from several randomized trials, in addition to multiple retrospective studies, that demonstrate not only survival benefit but also improved functional outcome with DC in appropriately selected patients. This article explores in detail the evidence for DC, nuances regarding patient selection, and applicability of DC for supratentorial intracerebral hemorrhage and posterior fossa ischemic and hemorrhagic stroke.