Improving the accuracy of epileptogenic zone localization in stereo EEG with machine learning algorithms.

The precise identification of the epileptogenic zone (EZ) is paramount in the presurgical evaluation of epilepsy patients to ensure successful surgical outcomes. The analysis of Stereo EEG, an instrumental tool for EZ localization, poses considerable challenges even for experienced epileptologists. Consequently, the development of machine learning (ML)-based computational tools for enhanced EZ localization is imperative. In this investigation, we developed ML models utilizing Stereo EEG from 15 patients, who remained seizure-free (Engel 1 a-d) following EZ resection, over an average follow-up period of 44.4 months. Utilizing Delphos and MNI detectors, spikes and High Frequency Oscillations (HFOs) were identified from Stereo EEG in Resected Zone (RZ) and non-Resected Zone (non-RZ). Linear and non-linear features were estimated from each modality using MATLAB. A total of 27,744 spikes, 7,790 ripples, and 7,632 fast ripples, along with their combinations, were employed to train the ML models. The Gradient Boosting classifier demonstrated the highest prediction accuracy of 98.5% for EZ localization in Mesial Temporal Lobe Epilepsy (MTLE) when trained with features derived from the spike-ripple combination. In the case of Neocortical Epilepsy (NE), the Extra Trees classifier achieved an accuracy of 87.6% when utilizing features from fast ripples. The Random Forest, Extra Trees, and Gradient Boosting algorithms were the most effective for predicting the RZ. Linear features outperformed non-linear features in predicting epileptogenic zones within the epileptic brain. Our study establishes the capability of ML methodologies in localizing epileptogenic zones with high accuracy. Future studies that focus on increasing the training sample size and incorporating more advanced machine learning (ML) algorithms have the potential to significantly improve the accuracy of these models in pinpointing epileptogenic networks. Additionally, implementing this ML approach across multiple research centers would contribute to the broader validation and generalizability of this technique.

Asymmetry index in anatomically symmetrized FDG-PET for improved epileptogenic focus detection in pharmacoresistant epilepsy.

OBJECTIVE: Positron emission tomography (PET) imaging has assumed an essential role in the presurgical evaluation of epileptogenic foci in drug-resistant epilepsy by identifying the hypometabolic cerebral cortex. The authors herein designed a pilot study to test a novel technique of PET asymmetry after anatomical symmetrization coregistered to MRI (PASCOM), utilizing interhemispheric metabolic asymmetry on interictal fluorine 18-labeled fluorodeoxyglucose (FDG)-PET to better localize the epileptogenic zone. METHODS: The authors analyzed interictal FDG-PET scans from 23 patients with drug-resistant epilepsy, mean (± SD) age 20.9 ± 13.1 years old, who had an Engel class I postsurgical outcome while followed up for > 12 months. T1-weighted and FLAIR MRI were used to create a patient-specific, structurally symmetrical template. The asymmetry index (AI) image was computed to detect the cerebral region of hypometabolism using different z-score threshold criteria to optimize sensitivity and specificity. The detected regions were compared with the resection cavity on postoperative MRI using predefined anatomical labels. PASCOM was compared with the visual analysis of FDG-PET by a nuclear medicine consultant blinded to other clinical data (VIS) and visual analysis during multidisciplinary team discussion (MDT). The efficacy of each technique was compared based on a performance score (S), sensitivity, specificity, and correct lateralization of epileptogenicity. RESULTS: The mean S was maximum (1.30 ± 1.23) for AI images when thresholded at z > 4 and retaining the cluster of more than 100 voxels containing the peak AI value (Z4C) with 73.03% sensitivity and 96.43% specificity. The mean S was minimum for VIS (0.27 ± 0.31). The mean sensitivity was maximum for MDT (85.04%) and minimum for Z5C (AI images thresholded at z > 5 and clustered; 59.47%), whereas the mean specificity was maximum for Z5C (97.77%) and minimum for VIS (64.60%). Z3C (AI images thresholded at z > 3 and clustered) and Z4C were able to correctly identify the side of epileptogenicity in all the patients. CONCLUSIONS: The PASCOM technique with a Z4C threshold had a maximum performance score with good sensitivity and specificity in localizing and lateralizing the epileptogenic zone. The described technique outperformed the conventional visual analysis of FDG-PET and hence warrants further prospective verification.

Localizing epileptogenic network from SEEG using non-linear correlation, mutual information and graph theory analysis.

The key challenge in epilepsy surgery is precise localization and removal of the epileptogenic zone (EZ) from the brain. Localization of the epileptogenic network by visual analysis of intracranial EEG is extremely difficult. In this retrospective study, we used interictal connectivity and graph theory analysis on intracranial EEG to better delineate the epileptogenic zone. Patients who underwent surgery for drug-refractory mesial temporal and neocortical epilepsy were included. Computational measures, such as h2 nonlinear correlation and mutual information, were used to estimate the interdependency of intracranial EEGs. We observed that the Out-Degree, Out-Strength, and Betweenness centrality (graph properties) were the best predictors of EZ. From the results, we also found that graph properties with a normalized value above 0.75 were found to be a useful measure to localize the EZ with a sensitivity of 87.88 and a specificity of 87.13. Our results also validate that frequently occurring types of interictal fast discharges (IFD) with connectivity measures and graph properties can better localize the EZ. We foresee graph theory analysis of interictal intracranial EEG data can help precise localization of EZ for cortical resection as well as in minimally invasive radiofrequency ablation of epileptogenic hubs. Further, prospective validation is required for clinical use.

Statistical asymmetry analysis of volumetric MRI and FDG PET in temporal lobe epilepsy.

PURPOSE: To analyze statistically derived threshold values of volumetric MRI and 18F fluorodeoxyglucose (FDG) PET asymmetry, independent of normative data, for non-invasive detection/exclusion of temporal lobe epilepsy (TLE). METHODS: We retrospectively analyzed amygdalohippocampal volumetry and temporal FDG PET metabolism in 33 patients (age: 29.27 ±â€¯8.56 years) who underwent surgery following Stereo-EEG implantation and had postsurgical seizure freedom lasting >12 months. The temporal lobe epilepsy group and the extratemporal lobe epilepsy (ETLE) group were compared. Percentage volume loss (PVL) was calculated from manually traced amygdalohippocampal volumetry whereas percentage metabolic loss (PML) was calculated from PET using amygdalohippocampal trace and temporal neocortical Brodmann areas (BA) template. RESULTS: Receiver operating characteristic (ROC) curve analysis identified a cutoff hippocampal PVL of 4.21% as the minimum indicating probable hippocampal involvement in seizure onset, with sensitivity of 88.89% and the specificity of 100% (p < 0.001). Region of interest (ROI)-based PML values in PET imaging showed a significant correlation with the presence of TLE in the TLE group of patients and its absence in the ETLE group of patients. Region of interest curve analysis yielded PML cutoffs of 5.77% and 8.36%, respectively, for the hippocampus and BA 38 (temporopolar neocortex) to detect TLE with the sensitivity of 72.7% and specificity of 77.8%. CONCLUSION: We describe statistical thresholds for asymmetry analysis of hippocampal volumetry and FDG PET to improve detection of TLE. These threshold parameters warrant further validation in prospective studies.

Outcome following surgery for insulo-opercular epilepsies.

OBJECTIVE: The purpose of this study was to evaluate the clinical outcome in patients with medically refractory epilepsy who had undergone resective or ablative surgery for suspected insulo-opercular epileptogenic foci. METHODS: The prospectively maintained database of patients undergoing epilepsy surgery was reviewed, and all patients who underwent insulo-opercular surgery for medically refractory epilepsy with a minimum of 12 months of postoperative follow-up were identified, excluding those who had insulo-opercular resection in combination with temporal lobectomy. The presurgical electroclinicoradiological data, stereo-EEG (SEEG) findings, resection/ablation patterns, surgical pathology, postoperative seizure outcome, and neurological complications were analyzed. RESULTS: Of 407 patients undergoing epilepsy surgery in a 5-year period at the Amrita Advanced Centre for Epilepsy, 24 patients (5.9%) who underwent exclusive insulo-opercular interventions were included in the study. Eleven (46%) underwent surgery on the right side, 12 (50%) on the left side, and the operation was bilateral in 1 (4%). The mean age at surgery was 24.5 ± 12.75 years. Onset of seizures occurred on average at 10.6 ± 9.7 years of life. Characteristic auras were identified in 66% and predominant seizure type was hypermotor (15.4%), automotor (15.4%), hypomotor (11.5%), or a mixed pattern. Seventy-five percent of the seizures recorded on scalp video-EEG occurred during sleep. The 3T MRI results were normal in 12 patients (50%). Direct single-stage surgery was undertaken in 5 patients, and SEEG followed by intervention in 19. Eighteen patients (75%) underwent exclusive resective surgery, 4 (16.7%) underwent exclusive volumetric radiofrequency ablation, and 2 (8.3%) underwent staged radiofrequency ablation and resective surgery. Immediate postoperative neurological deficits occurred in 10/24 (42%), which persisted beyond 12 postoperative months in 3 (12.5%). With a mean follow-up of 25.9 ± 14.6 months, 18 patients (75%) had Engel class I outcome, 3 (12.5%) had Engel class II, and 3 (12.5%) had Engel class III or IV. There was no statistically significant difference in outcomes between MRI-positive versus MRI-negative cases. CONCLUSIONS: Surgery for medically refractory epilepsy in insulo-opercular foci is less common and remains a challenge to epilepsy surgery centers. Localization is aided significantly by a careful study of auras and semiology followed by EEG and imaging. The requirement for SEEG is generally high. Satisfactory rates of seizure freedom were achievable independent of the MRI lesional/nonlesional status. Morbidity is higher for insulo-opercular epilepsy surgery compared to other focal epilepsies; hence, the practice and development of minimally invasive strategies for this subgroup of patients undergoing epilepsy surgery is perhaps most important.

Quantification of Epileptogenic Network From Stereo EEG Recordings Using Epileptogenicity Ranking Method.

Introduction: Precise localization of the epileptogenic zone is very essential for the success of epilepsy surgery. Epileptogenicity index (EI) computationally estimates epileptogenicity of brain structures based on the temporal domain parameters and magnitude of ictal discharges. This method works well in cases of mesial temporal lobe epilepsy but it showed reduced accuracy in neocortical epilepsy. To overcome this scenario, in this study, we propose Epileptogenicity Rank (ER), a modified method of EI for quantifying epileptogenicity, that is based on spatio-temporal properties of Stereo EEG (SEEG). Methods: Energy ratio during ictal discharges, the time of involvement and Euclidean distance between brain structures were used to compute the ER. Retrospectively, we localized the EZ for 33 patients (9 for mesial-temporal lobe epilepsy and 24 for neocortical epilepsy) using post op MRI and Engel 1 surgical outcome at a mean of 40.9 months and then optimized the ER in this group. Results: Epileptic network estimation based on ER successfully differentiated brain regions involved in the seizure onset from the propagation network. ER was calculated at multiple thresholds leading to an optimum value that differentiated the seizure onset from the propagation network. We observed that ER < 7.1 could localize the EZ in neocortical epilepsy with a sensitivity of 94.6% and specificity of 98.3% and ER < 7.3 in mesial temporal lobe epilepsy with a sensitivity of 95% and specificity of 98%. In non-seizure-free patients, the EZ localization based on ER pointed to brain area beyond the cortical resections. Significance: Methods like ER can improve the accuracy of EZ localization for brain resection and increase the precision of minimally invasive surgery techniques (radio-frequency or laser ablation) by identifying the epileptic hubs where the lesion is extensive or in nonlesional cases. For inclusivity with other clinical applications, this ER method has to be studied in more patients.

Intracranially injectable multi-siRNA nanomedicine for the inhibition of glioma stem cells.

BACKGROUND: Nanoparticle siRNA-conjugates are promising clinical therapeutics as indicated by recent US-FDA approval. In glioma stem cells (GSC), multiple stemness associated genes were found aberrant. We report intracranially injectable, multi-gene-targeted siRNA nanoparticle gel (NPG) for the combinatorial silencing of 3 aberrant genes, thus inhibiting the tumorogenic potential of GSCs. METHODS: NPG loaded with siRNAs targeted against FAK, NOTCH-1, and SOX-2 were prepared by the self-assembly of siRNAs with protamine-hyaluronic acid combination. Electron microscopy, DLS, and agarose gel electrophoresis were used for the physicochemical characterization. Cell transfection and gene-silencing efficiency were studied using human mesenchymal stem cells and rat C6 glioma-derived GSCs. Neurosphere inhibition was tested in vitro using GSCs derived from C6 cell line and glioma patient samples. Patient-derived xenograft model and orthotopic rat glioma model were used to test the effect of NPG on in vivo tumorigenicity. RESULTS: The siRNA nanoparticles with an average size ~ 250 nm and ~ 95% loading efficiency showed cellular uptake in ~95.5% GSCs. Simultaneous gene silencing of FAK, NOTCH-1, and SOX-2 led to the inhibition of neurosphere formation by GSCs, whereas normal stem cells remained unaffected and retained neuronal differentiation capability. GBM PDX models manifested significant impairment in the tumorigenic potential of NPG treated GSCs. Intracranial injection of NPG inhibited tumor growth in orthotopic rat brain tumor model. CONCLUSION: Intracranially injectable n-siRNA NPG targeted to multiple stem-cell signaling impairs glioma initiation capabilities of GSCs and inhibited tumor growth in vivo.

Current practices in epilepsy monitoring units (EMU) in India.

AIM: As an initial step to develop guidelines for epilepsy monitoring units (EMUs) appropriate for developing countries, we inquired the existing practices in EMUs in India. METHODS: After checking for the content and face validity as well for clarity, we sent a 52-item online non-anonymized questionnaire to all the 52 EMUs in India. RESULTS: The questionnaire was completed by 51 of the 52 EMUs (98% response rate). The majority of the EMUs are located in major cities and 51% are located in non-governmental corporate hospitals. There are total of 122 prolonged video-EEG monitoring (PVEM) beds in India and 70% EMUs have ≤2 beds. Approximately two-thirds of the EMUs have defined protocols for pre-procedure consent and risk assessment, management of seizure clusters and status epilepticus, continuous observation of patients, and peri­ictal testing. Only one-third of the EMUs have protocols for management of post-ictal psychosis, anti-suffocation pillows, and protected environment within bathrooms. The waiting period for PVEM is more (49.9 ± 101 vs. 4.9 ± 10.9 days; p = 0.04) and mean cost for 3-day PVEM is less (INR 8311 ± 9021 vs. 30,371 ± 17,563; p <0.0001) in public as compared to private hospitals. There was a negative correlation between cost of PVEM and the waiting period (r=-0.386; p = 0.01). Safety practices are similar in public and private hospitals. CONCLUSIONS: Although practices in EMUs in India vary widely, they are comparable to those in developed countries. India has severe shortage of EMUs and long waiting lists for affordable PVEM.

Contralateral insular epileptogenic hub causing seizure relapse after opercular focal cortical dysplasia surgery and response to radiofrequency thermocoagulation: illustrative case.

BACKGROUND: The reevaluation and management of seizure relapse following resective surgery in magnetic resonance imaging (MRI)-negative pharmacoresistant epilepsy remains a significant challenge. OBSERVATIONS: A 25-year-old right-handed male with medically refractory epilepsy presented with nonlocalizing electroencephalography (EEG) and MRI. Stereo-EEG (SEEG) implantation based on semiology and positron emission tomography imaging revealed a left frontal opercular focus with rapid bilateral insular ictal synchrony. The initial epileptogenic zone was resected and pathologically proven to be type 2A focal cortical dysplasia (FCD). Seizure relapse after 9 months was eventually reinvestigated, and repeat SEEG revealed a secondary epileptogenic focus in the contralateral insula. A novel technique of volumetric stereotactic radiofrequency ablation (vRFA) was utilized for the right insular focus, following which, the patient remains seizure-free for 20 months. He suffered a transient bilateral opercular syndrome following the second intervention that eventually resolved. LESSONS: The authors present clinical evidence to suggest epileptogenic nodes distant from the primary focus as a mechanism for seizure relapse following FCD surgery and the importance of bilateral insular SEEG coverage. The authors also describe a novel technique of minimally invasive vRFA that allows ablation of a larger volume of cerebral cortex when compared to conventional bedside SEEG electrode thermocoagulation.

Epileptic nystagmus due to a large parieto-temporo-occipital multilobar dysplasia.

We report a young female with medically refractory multiple daily seizures since childhood with semiology suggestive of an epileptic nystagmus. She had a large multilobar parieto-temporo-occipital dysplasia and became seizure-free after parieto-temporo-occipital disconnection with preserved visual functions.

First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and advances of new therapeutics.

The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio-facio-cutaneous syndrome, Legius syndrome, capillary malformation arterio-venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of India represents one of the largest populations in the world, yet remains underserved from an aspect of clinical genetics services. In an effort to bridge this gap, the First International Conference on RASopathies and Neurofibromatoses in Asia: Identification and Advances of New Therapeutics was held in Kochi, Kerala, India. These proceedings chronicle this timely and topical international symposium directed at discussing the best practices and therapies for individuals with neurofibromatoses and RASopathies.

Expanding the Spectrum of Robotic Assistance in Cranial Neurosurgery.

BACKGROUND: Robotic automation and haptic guidance have multiple applications in neurosurgery. OBJECTIVE: To define the spectrum of cranial procedures potentially benefiting from robotic assistance in a university hospital neurosurgical practice setting. METHODS: Procedures utilizing robotic assistance during a 24-mo period were retrospectively analyzed and classified as stereotactic or endoscopic based on the mode utilized in the ROSA system (Zimmer Biomet, Warsaw, Indiana). Machine log file data were retrospectively analyzed to compare registration accuracy using 3 different methods: (1) facial laser scanning, (2) bone fiduciary, or (3) skin fiduciary. RESULTS: Two hundred seven cranial neurosurgical procedures utilizing robotic assistance were performed in a 24-mo period. One hundred forty-five procedures utilizing the stereotactic mode included 33% stereotactic biopsy, 31% Stereo-EEG electrode insertion, 20% cranial navigation, 7% stereotactic catheter placement, 6% craniofacial stereotactic wire placement, 2% deep brain stimulation lead placement, and 1% stereotactic radiofrequency ablation. Sixty-two procedures utilizing the haptic endoscope guidance mode consisted of 48% transnasal endoscopic, 29% ventriculoscopic, and 23% endoport tubular access. Statistically significant differences in registration accuracies were observed with 0.521 ± 0.135 mm (n = 132) for facial laser scanning, 1.026 ± 0.398 mm for bone fiduciary (n = 22), and 1.750 ± 0.967 mm for skin fiduciary (n = 30; ANOVA, P < .001). CONCLUSION: The combination of accurate, automated stereotaxy with image and haptic guidance can be applied to a wide range of cranial neurosurgical procedures. The facial laser scanning method offered the best registration accuracy for the ROSA system based on our retrospective analysis.

Cerebrospinal Fluid Hyaluronan and Neurofibromatosis Type 2.

Neurofibromatosis type 2 (NF-2) is associated with mainly three types of recurrent benign tumors restricted to the central nervous system: schwannoma, meningioma and ependymoma. The absence of the protein NF2/Merlin causes an uninterrupted cell proliferation cascade originating from an abnormal interaction between an extracellular mucopolysaccharide, hyaluronan (HA), and schwann cell surface CD44 receptor, which has been identified as one of the central causative factors for schwannoma. Most tumors in NF-2 have a predilection to originate from either arachnoid cap cells or schwann cells of the cisternal portion of nerve rootlets that share a continuous exposure to cerebrospinal fluid (CSF). We hypothesize that the CSF HA may play a role in tumorigenesis in NF-2. In a prospective analysis over a period of one year, the levels of medium to low molecular weight HA (LMW HA) was estimated in the CSF of three subjects with central schwannomas and compared against that of age-sex matched controls, using Cetyltrimethylammonium bromide coupled turbidimetric assay and found to be seventeen-fold higher in the schwannoma subjects compared to the controls. HA was observed to be actively secreted by cultured schwannoma cells isolated from tumor tissues commensurate with their proliferation rate. On cell viability index analysis to compare the cell proliferation of astrocytoma cells with LMW HA vs. oligomeric HA (OHA), we found a decrease in cell proliferation of up to 30% with OHA. The study provides initial evidence that CSF HA may have a central role in the tumorigenesis of schwannoma in NF-2.

Myocardial injury after noncardiac surgery-incidence and predictors from a prospective observational cohort study at an Indian tertiary care centre.

Asymptomatic myocardial injury following noncardiac surgery (MINS) is an independent predictor of 30-day mortality and may go unrecognized based on standard diagnostic definition for myocardial infarction (MI). Given lack of published research on MINS in India, our study aims to determine incidence of MINS in patients undergoing noncardiac surgery at our tertiary care hospital, and evaluate the clinical characteristics including 30-day outcome.The prospective observational study included patients >65 years or >45 years with either hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), cerebrovascular accident (CVA), or peripheral arterial disease undergoing noncardiac surgery. MINS was peak troponin level of ≥0.03 ng/dL at 12-hour or 24-hour postoperative. All patients were followed for 30 days postoperatively. Predictors of MINS and mortality were analyzed using multivariate logistic regression. Patients categorized based on peak troponin cut-off values determined by receiver operating characteristic curve were analyzed by Kaplan-Meir test to compare the survival of patients between the groups.Among 1075 patients screened during 34-month period, the incidence of MINS was 17.5% (188/1075). Patients with DM, CAD, or who underwent peripheral nerve block anaesthesia were 1.5 (P < .01), 2 (P < .001), and 12 (P < .001) times, respectively, more likely to develop MINS than others. Patients with heart rates ≥96 bpm before induction of anesthesia were significantly associated with MINS (P = .005) and mortality (P = .02). The 30-day mortality in MINS cohort was 11.7% (22/188, 95% CI 7.5%-17.2%) vs 2.5% (23/887, 95% CI 1.7%-3.9%) in patients without MINS (P < .001). ECG changes (P = .002), peak troponin values >1 ng/mL (P = .01) were significantly associated with mortality. A peak troponin cut-off of >0.152 ng/mL predicted mortality among MINS patients at 72% sensitivity and 58% specificity. Lack of antithrombotic therapy following MINS was independent predictor of mortality (P < .001), with decreased mortality in patients who took post-op ASA (Aspirin) or Clopidogrel. Mortality among MINS patients with post-op ASA intake is 6.7% vs 12.1% among MINS patients without post-op ASA intake. Mortality among MINS patients with post-op Clopidogrel intake is 10.5% vs 11.8% among MINS patients without post-op Clopidogrel intake.A higher (17.5%, 95% CI 15-19%) incidence of MINS was observed in our patient cohort with significant association with 30-day mortality. Serial postoperative monitoring of troponin following noncardiac surgery as standard of care, would identify "at risk" patients translating to improved outcomes.

Trans-sylvian Approach to Microvascular Decompression for Trigeminal Neuralgia in Syndromic Cranial Base Settling.

BACKGROUND AND IMPORTANCE: The lateral suboccipital approach for microvascular decompression (MVD) of the trigeminal nerve has become a standard-of-care over the past several decades. Syndromic cranial base settling, a rare but known cause for trigeminal neuralgia (TN), poses significant dilemmas in clinical management. In such cases, distorted anatomy may render surgery via the suboccipital approach difficult or even impossible. CLINICAL PRESENTATION: A 34-yr-old male with osteogenesis imperfecta and severe basilar invagination suffered from TN that was refractory to medication and stereotactic radiosurgery. MVD of the fifth nerve root was performed via a pterional trans-sylvian approach after 3-dimensional trajectory modeling suggested the feasibility of this approach. He experienced complete resolution of TN and remains free of both pain and medications after 18 mo of follow-up. CONCLUSION: This microsurgical trajectory, previously undescribed for TN, provides good visualization of the trigeminal root entry zone, thereby offering an excellent surgical option for severe TN in the setting of abnormal posterior fossa anatomy.

Ventriculo-ureteral shunt insertion using percutaneous nephrostomy: a novel minimally invasive option in a patient with chronic hydrocephalus complicated by multiple distal ventriculoperitoneal shunt failures.

The management of ventriculoperitoneal (VP) shunt failure is a common problem in neurosurgical practice. On occasion, extraperitoneal sites for CSF diversion are required when shunting to the peritoneal cavity has failed after multiple attempts. The authors report a novel minimally invasive procedure allowing cannulation of the ureter for the purpose of ventriculo-ureteral (VU) shunting. Sixteen years prior to presentation, this 46-year-old woman had contracted tuberculous meningitis and had chronic hydrocephalus, with multiple distal shunt failures in recent months. A percutaneous nephrostomy was used to pass the distal catheter based on intraoperative retrograde pyelography. Following successful placement of the VU shunt, the patient's hydrocephalus stabilized and she returned to her regular functional status. The only long-term complication noted within 36 months of follow-up was a transient episode of electrolyte disturbance and dehydration associated with a diarrheal illness that responded to adequate hydration and salt supplementation. By its minimally invasive nature, this approach offers a reasonable extraperitoneal alternative after multiple distal shunt catheter failures have occurred.

Role of magnetoencephalography and stereo-electroencephalography in the presurgical evaluation in patients with drug-resistant epilepsy.

In selected patients with drug-resistant focal epilepsies (DRFE), who otherwise are likely to be excluded from epilepsy surgery (ES) because of the absence of a magnetic resonance imaging (MRI)-demonstrable lesion or discordant anatomo-electro-clinical (AEC) data, magnetoencephalography (MEG) may help to generate an AEC hypothesis and stereo-electroencephalography (SEEG) may help to verify the hypothesis and proceed with ES. The sensitivity of MEG is much better in localizing the spiking zone in relation to lateral temporal and extratemporal cortical regions compared to the mesial temporal structures. MEG has a dominant role in the presurgical evaluation of patients with MRI-negative DRFEs, insular epilepsies, and recurrent seizures after failed epilepsy surgeries, and in guiding placement of invasive electrodes. Moreover, postoperative seizure freedom is better if MEG spike source localized cortical region is included in the resection. When compared to subdural grid electrode recording, SEEG is less invasive and safer. Those who are otherwise destined to suffer from uncontrolled seizures and their consequences, SEEG guided ES is a worthwhile and a cost-effective option. Depending on the substrate pathology, there is > 80-90% chance of undergoing ES and 60-80% chance of becoming seizure-free following SEEG. Recent noninvasive techniques aimed at better structural imaging, delineating brain connectivity and recording specific intracerebral EEG patterns such as high frequency oscillations might decrease the need for SEEG; but more importantly, make SEEG exploration more goal-directed and hypothesis-driven.

Ventriculo-ureteral shunt insertion using percutaneous nephrostomy: a novel minimally invasive option in a patient with chronic hydrocephalus complicated by multiple distal ventriculoperitoneal shunt failures.

The management of ventriculoperitoneal (VP) shunt failure is a common problem in neurosurgical practice. On occasion, extraperitoneal sites for CSF diversion are required when shunting to the peritoneal cavity has failed after multiple attempts. The authors report a novel minimally invasive procedure allowing cannulation of the ureter for the purpose of ventriculo-ureteral (VU) shunting. Sixteen years prior to presentation, this 46-year-old woman had contracted tuberculous meningitis and had chronic hydrocephalus, with multiple distal shunt failures in recent months. A percutaneous nephrostomy was used to pass the distal catheter based on intraoperative retrograde pyelography. Following successful placement of the VU shunt, the patient's hydrocephalus stabilized and she returned to her regular functional status. The only long-term complication noted within 36 months of follow-up was a transient episode of electrolyte disturbance and dehydration associated with a diarrheal illness that responded to adequate hydration and salt supplementation. By its minimally invasive nature, this approach offers a reasonable extraperitoneal alternative after multiple distal shunt catheter failures have occurred.

Philadelphia chromosome-positive acute lymphoblastic leukemia: 8 years' experience from a tertiary care center in India.

INTRODUCTION: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients. It is also detected in 2% to 5% of children with ALL. Historically, patients with Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy combinations, short remission durations, and long-term disease-free survival rates of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized therapy of Ph-positive ALL. MATERIALS AND METHODS: This retrospective and descriptive single center study was carried out based on data retrieved of 508 patients treated for ALL from 2007 to 2014. Of these thirty patients were Ph-positive ALL and were available for analysis, and these patients were included in the study. Ph-positive ALL was defined as ALL carrying the t(9;22) translocation on standard karyotype and/or fluorescent in situ hybridization analysis and/or positivity for BCR-ABL fusion transcript detection by real-time quantitative polymerase chain reaction (RQ-PCR) analysis. Patients were treated with combination chemotherapy and oral TKIs and responses were classified as either CR defined by the absence of circulating blasts and <5% marrow blasts on a bone marrow examination done at the end of induction chemotherapy or failure, including persistent disease and early death. RESULTS: There were 30 (5.9%) cases of Ph-positive ALL out of a total of 508 cases of ALL with a median age of 27.5 years (range: 7-55). The choice of first line TKI was Imatinib in 25 (83.3 %) patients and Dasatinib in 1 (3.3 %) patient. Fourteen patients (46.6 %) had a CR, 3 (10 %) had a partial response (PR), 8 (26.6 %) had persistence of disease at the end of induction chemotherapy. The overall survival in those who received sequential chemotherapy followed by TKI (n = 4) was 28.5 months (95% CI 10.78 to 46.21 months) compared with 13.98 months (95% CI 6.04 to 21.97 months) for patients who received concurrent chemotherapy and TKI (n = 20); log rank (Mantel Cox) X2 = 8.33, P = 0.040), however limited sample precluded meaningful subgroup analysis. CONCLUSION: The results of our study showed that we still have a long way to go to match outcomes of western published series, even when the same treatment protocol is used, probably due to the underutilization of Allogeneic SCT as an option in first CR.