Palliation for catastrophic nonlocalizing epilepsy: a retrospective case series of complete corpus callosotomy at a single institution.

OBJECTIVE: In this study, the authors describe their 10-year single-institution experience with single-step complete corpus callosotomy (CCC) for seizure management in pediatric and adult patients with catastrophic, medically refractory, nonlocalizing epilepsy at Advent Health Orlando. METHODS: The authors conducted a retrospective observational study of patients aged 6 months to 49 years who underwent clinically indicated CCC for drug-resistant nonlocalizing epilepsy at Advent Health Orlando between July 2011 and July 2021. Follow-up ranged from 12 months to 10 years. RESULTS: Of the 101 patients (57% of whom were male) who met eligibility criteria, 81 were pediatric patients and 20 were ≥ 18 years. All patients had seizures that appeared poorly lateralized on both electroencephalograms and clinical semiological studies. Of 54 patients with drop seizures before CCC, 29 (54%) achieved stable freedom from drop seizures after CCC. Of the 101 patients, 14 (13.9%) experienced stable resolution of all types of clinical seizures (International League Against Epilepsy classes 1 and 2). The most common postoperative neurological complication was a transient disconnection syndrome, observed in 50% of patients; of those patients, 73% experienced syndrome resolution within 2 months after surgery, and all resolved by the 2-year follow-up. Formal neuropsychological test results were stable in 13 patients assessed after CCC. CONCLUSIONS: CCC is an effective and well-tolerated palliative surgical technique. In this study, drop attacks were reduced after CCC but could recur for the first time as late as 44 months after surgery. Other seizure types were also reduced postoperatively but could recur for the first time as late as 28 months after surgery. Nearly 14% of patients achieved stable and complete freedom from seizures after CCC. Re-evaluation after CCC can reveal lateralized seizure onset in some patients.

Efficacy of laser interstitial thermal therapy for biopsy-proven radiation necrosis in radiographically recurrent brain metastases.

Background: Laser interstitial thermal therapy (LITT) in the setting of post-SRS radiation necrosis (RN) for patients with brain metastases has growing evidence for efficacy. However, questions remain regarding hospitalization, local control, symptom control, and concurrent use of therapies. Methods: Demographics, intraprocedural data, safety, Karnofsky performance status (KPS), and survival data were prospectively collected and then analyzed on patients who consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 US centers. Data were monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan-Meier estimated survival. Results: Ninety patients met the inclusion criteria. Four patients underwent 2 ablations on the same day. Median hospitalization time was 32.5 hours. The median time to corticosteroid cessation after LITT was 13.0 days (0.0, 1229.0) and cumulative incidence of lesional progression was 19% at 1 year. Median post-procedure overall survival was 2.55 years [1.66, infinity] and 77.1% at one year as estimated by KaplanMeier. Median KPS remained at 80 through 2-year follow-up. Seizure prevalence was 12% within 1-month post-LITT and 7.9% at 3 months; down from 34.4% within 60-day prior to procedure. Conclusions: LITT for RN was not only again found to be safe with low patient morbidity but was also a highly effective treatment for RN for both local control and symptom management (including seizures). In addition to averting expected neurological death, LITT facilitates ongoing systemic therapy (in particular immunotherapy) by enabling the rapid cessation of steroids, thereby facilitating maximal possible survival for these patients.

Modeling a pesticide remediation strategy for preparative liquid chromatography using high-performance liquid chromatography.

BACKGROUND: Cannabis sativa L. also known as industrial hemp, is primarily cultivated as source material for cannabinoids cannabidiol (CBD) and ∆9-tetrahydrocannabinol (∆9-THC). Pesticide contamination during plant growth is a common issue in the cannabis industry which can render plant biomass and products made from contaminated material unusable. Remediation strategies to ensure safety compliance are vital to the industry, and special consideration should be given to methods that are non-destructive to concomitant cannabinoids. Preparative liquid chromatography (PLC) is an attractive strategy for remediating pesticide contaminants while also facilitating targeted isolation cannabinoids in cannabis biomass. METHODS: The present study evaluated the benchtop-scale suitability of pesticide remediation by liquid chromatographic eluent fractionation, by comparing retention times of 11 pesticides relative to 26 cannabinoids. The ten pesticides evaluated for retention times are clothianidin, imidacloprid, piperonyl butoxide, pyrethrins (I/II mixture), diuron, permethrin, boscalid, carbaryl, spinosyn A, and myclobutanil. Analytes were separated prior to quantification on an Agilent Infinity II 1260 high performance liquid chromatography with diode array detection (HPLC-DAD). The detection wavelengths used were 208, 220, 230, and 240 nm. Primary studies were performed using an Agilent InfinityLab Poroshell 120 EC-C18 3.0 × 50 mm column with 2.7 µm particle diameter, using a binary gradient. Preliminary studies on Phenomenex Luna 10 µm C18 PREP stationary phase were performed using a 150 × 4.6 mm column. RESULTS: The retention times of standards and cannabis matrices were evaluated. The matrices used were raw cannabis flower, ethanol crude extract, CO2 crude extract, distillate, distillation mother liquors, and distillation bottoms. The pesticides clothianidin, imidacloprid, carbaryl, diuron, spinosyn A, and myclobutanil eluted in the first 3.6 min, and all cannabinoids (except for 7-OH-CBD) eluted in the final 12.6 min of the 19-minute gradient for all matrices evaluated. The elution times of 7-OH-CBD and boscalid were 3.44 and 3.55 min, respectively. DISCUSSION: 7-OH-CBD is a metabolite of CBD and was not observed in the cannabis matrices evaluated. Thus, the present method is suitable for separating 7/11 pesticides and 25/26 cannabinoids tested in the six cannabis matrices tested. 7-OH-CBD, pyrethrins I and II (RTA: 6.8 min, RTB: 10.5 min), permethrin (RTA: 11.9 min, RTB: 12.2 min), and piperonyl butoxide (RTA: 8.3 min, RTB: 11.7 min), will require additional fractionation or purification steps. CONCLUSIONS: The benchtop method was demonstrated have congruent elution profiles using preparative-scale stationary phase. The resolution of pesticides from cannabinoids in this method indicates that eluent fractionation is a highly attractive industrial solution for pesticide remediation of contaminated cannabis materials and targeted isolation of cannabinoids.

Plasma Pharmacokinetics of Cannabidiol Following Oral Administration of Cannabidiol Oil to Dairy Calves.

Cannabidiol (CBD), the non-psychotropic component of cannabis, has drawn increased interest amongst some medical professionals for its potential therapeutic effects. Human and canine work has been done to describe CBD where it is already widely used, however, little is known about the effects of CBD in livestock species. The purpose of this descriptive study was to determine the pharmacokinetics (PK) of CBD in calves after a single oral exposure to CBD oil. Seven male Holstein calves received a single oral dose of 25 mg/mL CBD oil to achieve 5 mg/kg dose of CBD. Blood samples were collected for 48 (h) after dosing. The CBD geometric mean maximum concentration of 0.05 ug/mL was reached 7.5 h after administration. The geometric mean half-life was 23.02 h. Cannabidiol administered orally to cattle is slowly absorbed and has an extended elimination half-life compared to other species.

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss.

While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients.

Intracranial EEG and laser interstitial thermal therapy in MRI-negative insular and/or cingulate epilepsy: case series.

OBJECTIVE: The goal of this study was to assess the success rate and complications of stereo-electroencephalogra-phy (sEEG) and laser interstitial thermal therapy (LITT) in the treatment of nonlesional refractory epilepsy in cingulate and insular cortex. METHODS: The authors retrospectively analyzed the treatment response in 9 successive patients who underwent insular or cingulate LITT for nonlesional refractory epilepsy at their center between 2011 and 2019. Localization of seizures was based on inpatient video-EEG monitoring, neuropsychological testing, 3-T MRI, PET scan, magnetoencephalography scan, and/or ictal SPECT scan. Eight patients underwent sEEG, and 1 patient had implantation of both sEEG electrodes and subdural grids for localization of epileptogenic zones. LITT was performed in 5 insular cases (4 left and 1 right) and 3 cingulate cases (all left-sided). One patient also underwent both insular and cingulate LITT on the left side. All of the patients who underwent insular LITT as well as 2 of the 3 who underwent cingulate LITT were right-hand dominant. The patient who underwent insular plus cingulate LITT was also right-hand dominant. RESULTS: Following LITT, 67% of the patients were seizure free (Engel class I) at follow-up (mean 1.35 years, range 0.6-2.8 years). All patients responded favorably to treatment (Engel class I-III). Two patients developed small intracranial hemorrhages during the sEEG implantation that did not require surgical management. One patient developed a large intracranial hemorrhage during an insular LITT procedure that did require surgical management. That patient experienced aphasia, incoordination, and hemiparesis, which resolved with inpatient rehabilitation. No permanent neurological deficits were noted in any of the patients at last follow-up. Neuropsychological status was stable in this cohort before and after LITT. CONCLUSIONS: sEEG can be safely used to localize seizures originating from insular and cingulate cortex. LITT can successfully treat seizures arising from these deep-seated structures. The insula and cingulum should be evaluated more frequently for seizure onset zones.

A prospective multicenter study of laser ablation for drug resistant epilepsy - One year outcomes.

OBJECTIVE: To report one-year seizure outcomes, procedural data, and quality of life scores following laser interstitial thermal therapy (LITT) of epileptogenic foci. METHODS: Data from an ongoing prospective, multi-center registry were assessed. Procedural information, Engel seizure outcomes, and quality of life (QoL) scores were analyzed. A responder analysis was performed to better understand potential clinical characteristics that could influence seizure outcome. RESULTS: Sixty patients have been enrolled into LAANTERN (Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System) specifically for epilepsy treatment, of which 42 reached one year follow up. Engel I outcome was achieved in 64.3 % at one year follow up. Patients with mesial temporal lobe epilepsy (MTLE) comprised 56.7 % of this cohort of multiple epilepsy types. Other significant etiologies included focal cortical dysplasia, hypothalamic hamartoma, cavernoma, heterotopias, and tuberous sclerosis. Median length of stay was 32.7 h. At discharge, head pain score averaged 1.4 ± 2.1 on a scale from 1 to 10. Five adverse events were reported, one categorized as serious. Seizure worry and social functioning scores improved significantly in quality of life measures. SIGNIFICANCE: Surgical treatment with LITT for epileptic foci is a safe and effective treatment option for people with drug resistant epilepsy. Our multicenter prospective seizure outcomes continue to expand published LITT experience in MTLE as well as non-MTLE epilepsies. The minimally invasive nature allows for short hospitalizations with minimal reported pain and discomfort.

Deep Learning Provides Exceptional Accuracy to ECoG-Based Functional Language Mapping for Epilepsy Surgery.

The success of surgical resection in epilepsy patients depends on preserving functionally critical brain regions, while removing pathological tissues. Being the gold standard, electro-cortical stimulation mapping (ESM) helps surgeons in localizing the function of eloquent cortex through electrical stimulation of electrodes placed directly on the cortical brain surface. Due to the potential hazards of ESM, including increased risk of provoked seizures, electrocorticography based functional mapping (ECoG-FM) was introduced as a safer alternative approach. However, ECoG-FM has a low success rate when compared to the ESM. In this study, we address this critical limitation by developing a new algorithm based on deep learning for ECoG-FM and thereby we achieve an accuracy comparable to ESM in identifying eloquent language cortex. In our experiments, with 11 epilepsy patients who underwent presurgical evaluation (through deep learning-based signal analysis on 637 electrodes), our proposed algorithm obtained an accuracy of 83.05% in identifying language regions, an exceptional 23% improvement with respect to the conventional ECoG-FM analysis (∼60%). Our findings have demonstrated, for the first time, that deep learning powered ECoG-FM can serve as a stand-alone modality and avoid likely hazards of the ESM in epilepsy surgery. Hence, reducing the potential for developing post-surgical morbidity in the language function.

Altered integrity of corpus callosum in generalized epilepsy in relation to seizure lateralization after corpus callosotomy.

OBJECTIVE: Generalized-onset seizures are usually conceptualized as engaging bilaterally distributed networks with no clear focus. However, the authors previously reported a case series demonstrating that in some patients with generalized-onset seizures, focal seizure onset could be discovered after corpus callosotomy. The corpus callosum is considered to be a major pathway for seizure generalization in this group of patients. The authors hypothesized that, in patients with generalized-onset seizures, the structure of the corpus callosum could be different between patients who have lateralized seizures and those who have nonlateralized seizures after corpus callosotomy. The authors aimed to evaluate the structural difference through statistical analysis of diffusion tensor imaging (DTI) scalars between these two groups of patients. METHODS: Thirty-two patients diagnosed with generalized-onset motor seizures and without an MRI lesion were included in this study. Among them, 16 patients developed lateralized epileptic activities after corpus callosotomy, and the remaining 16 patients continued to have nonlateralized seizures after corpus callosotomy. Presurgical DTI studies were acquired to quantify the structural integrity of the corpus callosum. RESULTS: The DTI analysis showed significant reduction of fractional anisotropy (FA) and increase in radial diffusivity (RD) in the body of the corpus callosum in the lateralized group compared with the nonlateralized group. CONCLUSIONS: The authors' findings indicate the existence of different configurations of bilateral epileptic networks in generalized epilepsy. Generalized seizures with focal onset relying on rapid spread through the corpus callosum might cause more structural damage related to demyelination in the corpus callosum, showing reduced FA and increased RD. This study suggests that presurgical DTI analysis of the corpus callosum might predict the seizure lateralization after corpus callosotomy.

Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN): 12-Month Outcomes and Quality of Life After Brain Tumor Ablation.

BACKGROUND: Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality-of-life (QoL) data. OBJECTIVE: To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms. METHODS: Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur. RESULTS: A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors. CONCLUSION: Results from the ongoing LAANTERN registry demonstrate that LITT stabilizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real-world registry and comparative to published literature.

Epilepsy Surgery in Children versus Adults.

Epilepsy is one of the most common chronic neurological disorder affecting 6-7 per 1000 worldwide. Nearly one-third of patients with newly diagnosed epilepsy continue to have recurrent seizures despite adequate trial of more than two anti-seizure drugs : drug-resistant epilepsy (DRE). Children with DRE often experience cognitive and psychosocial co-morbidities requiring more urgent and aggressive treatment than adults. Epilepsy surgery can result in seizure-freedom in approximately two-third of children with improvement in cognitive development and quality of life. Understanding fundamental differences in etiology, co-morbidity, and neural plasticity between children and adults is critical for appropriate selection of surgical candidates, appropriate presurgical evaluation and surgical approach, and improved overall outcome.

Safety of Autologous Umbilical Cord Blood Therapy for Acquired Sensorineural Hearing Loss in Children.

BACKGROUND AND OBJECTIVES: Sensorineural hearing loss (SNHL) in children is associated with neurocognitive morbidity. The cause of SNHL is a loss of hair cells in the organ of Corti. There are currently no reparative treatments for SNHL. Numerous studies suggest that cord blood mononuclear cells (human umbilical cord blood, hUCB) allow at least partial restoration of SNHL by enabling repair of a damaged organ of Corti. Our objective is to determine if hUCB is a safe treatment for moderate to severe acquired SNHL in children. Subjects and. METHODS: Eleven children aged 6 months to 6 years with moderate to severe acquired SNHL were treated with intravenous autologous hUCB. The cell dose ranged from 8 to 30 million cells/kg body weight. Safety was assessed by measuring systemic hemodynamics during hUCB infusion. Infusion-related toxicity was evaluated by measuring neurologic, hepatic, renal and pulmonary function before and after infusion. Auditory function, auditory verbal language assessments and MRI with diffusion tensor imaging (DTI) were obtained before and after treatment. RESULTS: All patients survived, and there were no adverse events. No infusionrelated changes in hemodynamics occurred. No infusion-related toxicity was recorded. Five subjects experienced a reduction in auditory brainstem response (ABR) thresholds. Four of those 5 subjects also experienced an improvement in cochlear nerve latencies. Comparison of MRI with DTI sequences obtained before and after treatment revealed increased fractional anisotropy in the primary auditory cortex in three of five subjects with reduced ABR thresholds. Statistically significant (p<0.05) reductions in ABR thresholds were identified. CONCLUSIONS: TIntravenous hUCB is feasible and safe in children with SNHL.

Usefulness of intraoperative insular electrocorticography in modified functional hemispherectomy.

BACKGROUND: The insular cortex is not routinely removed in modified functional hemispherectomy due to the risk of injury to the main arteries and to deep structures. Our study evaluates the safety and usefulness of applying intraoperative electrocorticography (ECoG) on the insular during the hemispherectomy. METHODS: We included all patients who underwent insular ECoG during a modified functional hemispherectomy from 2012 to 2015. After the surgery, the decision for further resection of the insular cortex was made based on the presence of electrographic seizures on ECoG. RESULTS: The study included 19 patients (age, 6.4 ± 4.7 years, mean ± standard deviation). Electrographic seizures were identified in 5 patients (26.3%). Sixteen of the 19 patients (84.2%) became seizure-free with a follow-up duration of 3.1 ± 0.6 years and no vascular complication occurred. CONCLUSIONS: Intraoperative insular ECoG monitoring can be performed safely while providing a tailored approach for insular resection during modified hemispherectomy.

Technical descriptions of four hemispherectomy approaches: From the Pediatric Epilepsy Surgery Meeting at Gothenburg 2014.

Hemispherectomy is a complex multistep procedure with a steep learning curve. Several surgical approaches have been developed, but each requires considerable practice to master. Four experienced pediatric neurosurgeons, who participated in the 2014 Gothenburg Pediatric Epilepsy Surgery Meeting, provided succinct technical summaries of four hemispherectomy approaches: modified functional hemispherectomy, peri-insular hemispherotomy, parasagittal hemispherotomy, and endoscopic-assisted hemispherotomy. No clinical or outcome data are included. Our intention is to reduce the slope and length of the learning curve for surgeons and to improve the understanding of the technical details of hemispherectomy surgery by nonsurgeonmembers of epilepsy teams.

Impact of intraoperative 3-T MRI with diffusion tensor imaging on hemispherectomy.

OBJECTIVE Hemispherectomy can produce remarkable seizure control of medically intractable hemispheric epilepsy in children, but some patients continue to have seizures after surgery. A frequent cause of treatment failure is incomplete surgical disconnection of the abnormal hemisphere. This study explores whether intraoperative 3-T MRI with diffusion tensor imaging (DTI) during hemispherectomy can identify areas of incomplete disconnection and allow complete disconnection during a single surgery. METHODS The charts of 32 patients with epilepsy who underwent hemispherectomy between January 2012 and July 2014 at the Florida Hospital for Children were reviewed. Patients were grouped as having had curative or palliative hemispherectomy. To assess the completeness of disconnection when the surgeon considered the operation completed, intraoperative 3-T MRI-DTI was performed. If incomplete disconnection was identified, additional surgery was performed until MRI-DTI sequences confirmed satisfactory disconnection. Seizure outcome data were collected via medical records at last follow-up. RESULTS Of 32 patients who underwent hemispherectomy, 23 had curative hemispherectomy and 9 had palliative hemispherectomy. In 11 of 32 surgeries, the first intraoperative MRI-DTI sequences suggested incomplete disconnection and additional surgery followed by repeat MRI-DTI was performed. Complete disconnection was accomplished in 30 of 32 patients (93.8%). Two of 32 disconnections (6.3%) were incomplete on postoperative imaging. Cross-sectional results showed that 21 of 23 patients (91.3%) who had curative hemispherectomy remained free of seizures (International League Against Epilepsy Class 1) at a median follow-up of 1.7 years (range 0.4-2.9 years). The longitudinal seizure freedom after curative hemispherectomy was 95.2% (SE 0.05) at 6 months, 90.5% (SE 0.06) at 1 year, and 90.5% (SE 0.05) at 2 years. CONCLUSIONS Intraoperative 3-T MRI-DTI sequences can identify incomplete disconnection during hemispherectomy and allow higher rates of complete disconnection in a single surgery. Higher rates of complete disconnection seem to achieve better seizure-free outcome following modified functional hemispherectomy.

Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals.

Simultaneous bilateral onset and bi-synchrony epileptiform discharges in electroencephalogram (EEG) remain hallmarks for generalized seizures. However, the possibility of an epileptogenic focus triggering rapidly generalized epileptiform discharges has been documented in several studies. Previously, a new multi-stage surgical procedure using bilateral intracranial EEG (iEEG) prior to and post complete corpus callosotomy (CC) was developed to uncover seizure focus in non-lateralizing focal epilepsy. Five patients with drug-resistant generalized epilepsy who underwent this procedure were included in the study. Their bilateral iEEG findings prior to complete CC showed generalized epileptiform discharges with no clear lateralization. Nonetheless, the bilateral ictal iEEG findings post complete CC indicated lateralized or localized seizure onset. This study hypothesized that brain functional connectivity analysis, applied to the pre CC bilateral iEEG recordings, could help identify focal epileptogenic networks in generalized epilepsy. The results indicated that despite diffuse epileptiform discharges, focal features can still be observed in apparent generalized seizures through brain connectivity analysis. The seizure onset localization/lateralization from connectivity analysis demonstrated a good agreement with the bilateral iEEG findings post complete CC and final surgical outcomes. Our study supports the role of focal epileptic networks in generalized seizures.

CortiQ-based Real-Time Functional Mapping for Epilepsy Surgery.

PURPOSE: To evaluate the use of the cortiQ-based mapping system (g.tec medication engineering GmbH, Austria) for real-time functional mapping (RTFM) and to compare it to results from electrical cortical stimulation mapping (ESM) and functional magnetic resonance imaging (fMRI). METHODS: Electrocorticographic activity was recorded in 3 male patients with intractable epilepsy by using cortiQ mapping system and analyzed in real time. Activation related to motor, sensory, and receptive language tasks was determined by evaluating the power of the high gamma frequency band (60-170 Hz). The sensitivity and specificity of RTFM were tested against ESM and fMRI results. RESULTS: "Next-neighbor" approach demonstrated [sensitivity/specificity %] (1) RTFM against ESM: 100.00/79.70 for hand motor; 100.00/73.87 for hand sensory; -/87 for language (it was not identified by the ESM); (2) RTFM against fMRI: 100.00/84.4 for hand motor; 66.70/85.35 for hand sensory; and 87.85/77.70 for language. CONCLUSIONS: The results of the quantitative "next-neighbor" RTFM evaluation were concordant to those from ESM and fMRI. The RTFM correlates well with localization of hand motor function provided by ESM and fMRI, which may offer added localization in the operating room and guidance for extraoperative ESM mapping. Real-time functional mapping correlates with fMRI language activation when ESM findings are negative. It has fewer limitations than ESM and greater flexibility in activation paradigms and measuring responses.

Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe traumatic brain injury in children.

OBJECTIVES: The devastating effect of traumatic brain injury is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure due to cerebral edema. The treatment effect of cell-based therapies in the acute post-traumatic brain injury period has not been clinically studied although preclinical data demonstrate that bone marrow-derived mononuclear cell infusion down-regulates the inflammatory response. Our study evaluates whether pediatric traumatic brain injury patients receiving IV autologous bone marrow-derived mononuclear cells within 48 hours of injury experienced a reduction in therapeutic intensity directed toward managing elevated intracranial pressure relative to matched controls. DESIGN: The study was a retrospective cohort design comparing pediatric patients in a phase I clinical trial treated with IV autologous bone marrow-derived mononuclear cells (n = 10) to a control group of age- and severity-matched children (n = 19). SETTING: The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000 to 2008. PATIENTS: Study patients were 5-14 years with postresuscitation Glasgow Coma Scale scores of 5-8. INTERVENTIONS: The treatment group received 6 million autologous bone marrow-derived mononuclear cells/kg body weight IV within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our traumatic brain injury management protocol, derived from American Association of Neurological Surgeons guidelines. MEASUREMENTS AND MAIN RESULTS: The primary measure was the Pediatric Intensity Level of Therapy scale used to quantify treatment of elevated intracranial pressure. Secondary measures included the Pediatric Logistic Organ Dysfunction score and days of intracranial pressure monitoring as a surrogate for length of neurointensive care. A repeated-measure mixed model with marginal linear predictions identified a significant reduction in the Pediatric Intensity Level of Therapy score beginning at 24 hours posttreatment through week 1 (p < 0.05). This divergence was also reflected in the Pediatric Logistic Organ Dysfunction score following the first week. The duration of intracranial pressure monitoring was 8.2 ± 1.3 days in the treated group and 15.6 ± 3.5 days (p = 0.03) in the time-matched control group. CONCLUSIONS: IV autologous bone marrow-derived mononuclear cell therapy is associated with lower treatment intensity required to manage intracranial pressure, associated severity of organ injury, and duration of neurointensive care following severe traumatic brain injury. This may corroborate preclinical data that autologous bone marrow-derived mononuclear cell therapy attenuates the effects of inflammation in the early post-traumatic brain injury period.

Bilateral intracranial EEG with corpus callosotomy may uncover seizure focus in nonlocalizing focal epilepsy.

PURPOSE: To evaluate the value of a new multi-stage surgical procedure using bilateral intracranial electroencephalogram (iEEG) prior and post complete corpus callosotomy (CC) for epileptogenic focus localization. METHOD: Thirty patients with drug-resistant epilepsy underwent bilateral iEEG monitoring to localize epileptogenic focus for surgical treatment. Among them, bisynchronous epileptogenic activities were found in 9 pediatric patients. These 9 patients then received complete CC and continued bilateral iEEG monitoring for further seizure localization. Final surgical treatment decisions were made based on the bilateral iEEG findings post complete CC. The entire multi-stage procedure was performed during the same hospital stay. We retrospectively studied the data from the 9 patients. RESULTS: Seizure onset was lateralized in 3 patients who later received functional hemispherectomy. In another 4 patients, seizure onset was localized, resulting in resective surgery. Bilateral multiple subpial transection was performed on 1 patient with identified bilateral independent seizure onset. One patient did not have seizures following complete CC leading to removal of electrodes without any further resection. Subsequent follow-up showed favorable outcome in all patients: seizure-free in 7, more than 90% reduction in 2. None of the patients experienced surgery related complications during the procedure and follow-up period. CONCLUSION: The multi-stage surgical procedure utilizing iEEG monitoring with CC is a viable option for select patients with catastrophic non-localizing epilepsy. Further study is necessary to find the optimal selection criteria for use of this novel approach.