Failure to breathe persists without air hunger or alarm following amygdala seizures.

Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a potentially novel approach combining electrical stimulation with functional MRI, we found that amygdala stimulation altered blood oxygen level-dependent (BOLD) activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.

Outcome of stereo-electroencephalography with single-unit recording in drug-refractory epilepsy.

OBJECTIVE: The aim of this study was to evaluate the utility and safety of "hybrid" stereo-electroencephalography (SEEG) in guiding epilepsy surgery and in providing information at single-neuron levels (i.e., single-unit recording) to further the understanding of the mechanisms of epilepsy and the neurocognitive processes unique to humans. METHODS: The authors evaluated 218 consecutive patients undergoing SEEG procedures from 1993 through 2018 at a single academic medical center to assess the utility and safety of this technique in both guiding epilepsy surgery and providing single-unit recordings. The hybrid electrodes used in this study contained macrocontacts and microwires to simultaneously record intracranial EEG and single-unit activity (hybrid SEEG). The outcomes of SEEG-guided surgical interventions were examined, as well as the yield and scientific utility of single-unit recordings in 213 patients who participated in the research involving single-unit recordings. RESULTS: All patients underwent SEEG implantation by a single surgeon and subsequent video-EEG monitoring (mean of 10.2 electrodes per patient and 12.0 monitored days). Epilepsy networks were localized in 191 (87.6%) patients. Two clinically significant procedural complications (one hemorrhage and one infection) were noted. Of 130 patients who underwent subsequent focal epilepsy surgery with a minimum 12-month follow-up, 102 (78.5%) underwent resective surgery and 28 (21.5%) underwent closed-loop responsive neurostimulation (RNS) with or without resection. Seizure freedom was achieved in 65 (63.7%) patients in the resective group. In the RNS group, 21 (75.0%) patients achieved 50% or greater seizure reduction. When the initial period of 1993 through 2013 before responsive neurostimulator implantation in 2014 was compared with the subsequent period of 2014 through 2018, the proportion of SEEG patients undergoing focal epilepsy surgery grew from 57.9% to 79.7% due to the advent of RNS, despite a decline in focal resective surgery from 55.3% to 35.6%. A total of 18,680 microwires were implanted in 213 patients, resulting in numerous significant scientific findings. Recent recordings from 35 patients showed a yield of 1813 neurons, with a mean yield of 51.8 neurons per patient. CONCLUSIONS: Hybrid SEEG enables safe and effective localization of epileptogenic zones to guide epilepsy surgery and provides unique scientific opportunities to investigate neurons from various brain regions in conscious patients. This technique will be increasingly utilized due to the advent of RNS and may prove a useful approach to probe neuronal networks in other brain disorders.

Preliminary Experience Suggests the Addition of Choroid Plexus Cauterization to Functional Hemispherectomy May Reduce Posthemispherectomy Hydrocephalus.

BACKGROUND: Cerebral hemispherectomy can effectively treat unihemispheric epilepsy. However, posthemispherectomy hydrocephalus (PHH), a serious life-long complication, remains prevalent, requiring careful considerations in technique selection and postoperative management. In 2016, we began incorporating open choroid plexus cauterization (CPC) into our institution's hemispherectomy procedure in an attempt to prevent PHH. OBJECTIVE: To determine whether routine CPC prevented PHH without exacerbating hemispherectomy efficacy or safety. METHODS: A retrospective review of consecutive patients who underwent hemispherectomy for intractable epilepsy between 2011 and 2021 was performed. Multivariate logistic regression was used to identify factors independently associated with PHH requiring cerebrospinal fluid (CSF) shunting. RESULTS: Sixty-eight patients were included in this study, of whom 26 (38.2%) underwent CPC. Fewer patients required CSF shunting in the CPC group (7.7% vs 28.7%, P = .033) and no patients who underwent de novo hemispherectomy with CPC developed PHH. Both cohorts experienced seizure freedom (65.4% vs 59.5%, P = .634) and postoperative complications, including infection (3.8% vs 2.4%, P = .728), hemorrhage (0.0% vs 2.4%, P = .428), and revision hemispherectomy (19.2% vs 14.3%, P = .591) at similar rates. Patients without CPC had greater odds of developing PHH requiring CSF shunting (odds ratio = 8.36, P = .026). The number needed to treat with CPC to prevent an additional case of PHH was 4.8, suggesting high effectiveness. CONCLUSION: Preventing PHH is critical. Our early experience demonstrated that routinely incorporating CPC into hemispherectomy effectively prevents PHH without causing additional complications, especially in first-time hemispherectomies. A multicenter randomized controlled trial with long-term follow-up is required to corroborate the findings of our single-institutional case series and determine whether greater adoption of this technique is justified.

Midline Brain Shift After Hemispheric Surgery: Natural History, Clinical Significance, and Association With Cerebrospinal Fluid Diversion.

BACKGROUND: Hemispherectomy and its modern variants are effective surgical treatments for medically intractable unihemispheric epilepsy. Although some complications such as posthemispherectomy hydrocephalus are well documented, midline brain shift (MLBS) after hemispheric surgery has only been described anecdotally and never formally studied. OBJECTIVE: To assess the natural history and clinical relevance of MLBS and determine whether cerebrospinal fluid (CSF) shunting of the ipsilateral surgical cavity exacerbates MLBS posthemispheric surgery. METHODS: A retrospective review of consecutive pediatric patients who underwent hemispheric surgery for intractable epilepsy and at least 6 months of follow-up at UCLA between 1994 and 2018 was performed. Patients were grouped by MLBS severity, shunt placement, valve type, and valve opening pressure (VOP). MLBS was evaluated using the paired samples t-test and analysis of covariance adjusting for follow-up time and baseline postoperative MLBS. RESULTS: Seventy patients were analyzed, of which 23 (33%) required CSF shunt placement in the ipsilateral surgical cavity for posthemispherectomy hydrocephalus. MLBS increased between first and last follow-up for nonshunted (5.3 ± 4.9-9.7 ± 6.6 mm, P < .001) and shunted (6.6 ± 3.5-16.3 ± 9.4 mm, P < .001) patients. MLBS progression was greater in shunted patients (P = .001). Shunts with higher VOPs did not increase MLBS relative to nonshunted patients (P = .834), whereas MLBS increased with lower VOPs (P = .001). Severe MLBS was associated with debilitating headaches (P = .048). CONCLUSION: Patients undergoing hemispheric surgery often develop postoperative MLBS, ie, exacerbated by CSF shunting of the ipsilateral surgical cavity, specifically when using lower VOP settings. MLBS exacerbation may be related to overshunting. Severe MLBS is associated with debilitating headaches.

Intracranial pressure monitoring during stereoelectroencephalography implantation: a technical note.

Stereoelectroencephalography (SEEG) has become increasingly employed as a critical component of epilepsy workups for patients with drug-resistant epilepsy when information from noninvasive studies is not conclusive and sufficient to guide epilepsy surgery. Although exceedingly rare, clinically significant hemorrhagic complications can be caused during SEEG implantation procedures. Intracranial hemorrhage (ICH) can be difficult to recognize due to the minimally invasive nature of SEEG. The authors describe their technique using a commercially available intraparenchymal intracranial pressure (ICP) monitor as a method for early intraoperative detection of ICH during SEEG implantation. Between May 2019 and July 2021, 18 pediatric patients underwent SEEG implantation at a single, freestanding children's hospital with the use of an ICP monitor during the procedure. No patients experienced complications resulting from this technique. The authors have relayed their rationale for ICP monitor use during SEEG, the technical considerations, and the safety profile. In addition, they have reported an illustrative case in which the ICP monitor proved crucial in early detection of ICH during SEEG implantation.

Real-World Preliminary Experience With Responsive Neurostimulation in Pediatric Epilepsy: A Multicenter Retrospective Observational Study.

BACKGROUND: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited. OBJECTIVE: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients. METHODS: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (<18 yr) and young adults (>18 yr) and compared with prior literature pertaining to adult patients. RESULTS: Of 35 patients identified, 17 were <18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had <50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in our cohort or between our cohort and the adult literature. CONCLUSION: These preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age. Data regarding long-term efficacy and safety in children will be critical to optimize patient selection.

The Wishbone: A Cranial Midline Localizing Device.

OBJECTIVE: The Wishbone device is designed to enable surgeons to quickly and accurately localize the cranial midline. It is intended to be of particular use when localizing the burr hole site during posterior ventriculoperitoneal shunt (VPS) surgery. METHODS: The Wishbone is a simple mechanical device with 2 adjustable caliper arms that reversibly attach to a patient's left and right external auditory canals. The Wishbone's laser localizer illuminates the midline scalp. The Wishbone was used to localize the posterior midline in a pilot series of patients undergoing VPS surgery. Midline localization and ventricular catheter placement accuracy were determined using findings from postoperative computed tomography scans. RESULTS: The Wishbone is a mechanically robust device and proved easy for surgeons to use. Forty patients underwent VPS surgery using the Wishbone to localize the posterior midline. The localization procedure took less than 3 minutes. The average distance separating the Wishbone-localized midline scalp location and the computed tomography-defined anatomical midline was 2.9 mm (95% confidence interval 1.6-4.1 mm). In all cases, the ventricular catheter entered the ipsilateral lateral ventricle. The catheter tips were placed in the ipsilateral (n = 34) or contralateral (n = 5) frontal horn in all but 1 patient. In 1 patient, the catheter tip entered the parenchyma due to a burr hole localization error in the rostrocaudal dimension, unrelated to the Wishbone. CONCLUSIONS: We describe a simple, efficient, and cost-effective system for accurately localizing the posterior cranial midline. A larger patient series is required to definitively compare its clinical utility relative to frameless stereotaxis-based midline localization methods.

Genome-wide DNA methylation investigation of glucocorticoid exposure within buccal samples.

AIM: Glucocorticoids play a major role in regulating the stress response, and an imbalance of glucocorticoids has been implicated in stress-related disorders. Within mouse models, CpGs across the genome have been shown to be differentially methylated in response to glucocorticoid treatment, and using the Infinium 27K array, it was shown that humans given synthetic glucocorticoids had DNA methylation (DNAm) changes in blood. However, further investigation of the extent to which glucocorticoids affect DNAm across a larger proportion of the genome is needed. METHODS: Buccal samples were collected before and after synthetic glucocorticoid treatment in the context of a dental procedure. This included 30 tooth extraction surgery patients who received 10 mg of dexamethasone. Genome-wide DNAm was assessed with the Infinium HumanMethylationEPIC array. RESULTS: Five CpGs showed genome-wide significant DNAm changes that were >10%. These differentially methylated CpGs were in or nearest the following genes: ZNF438, KLHDC10, miR-544 or CRABP1, DPH5, and WDFY2. Using previously published datasets of human blood gene expression changes following dexamethasone exposure, a significant proportion of genes with false-discovery-rate-adjusted significant CpGs were also differentially expressed. A pathway analysis of the genes with false-discovery-rate-adjusted significant CpGs revealed significant enrichment of olfactory transduction, pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and steroid hormone biosynthesis pathways. CONCLUSION: High-dose synthetic glucocorticoid administration in the setting of a dental procedure was significantly associated with DNAm changes within buccal samples. These findings are consistent with prior findings of an influence of glucocorticoids on DNAm in humans.

Drug repositioning in epilepsy reveals novel antiseizure candidates.

Objective: Epilepsy treatment falls short in ~30% of cases. A better understanding of epilepsy pathophysiology can guide rational drug development in this difficult to treat condition. We tested a low-cost, drug-repositioning strategy to identify candidate epilepsy drugs that are already FDA-approved and might be immediately tested in epilepsy patients who require new therapies. Methods: Biopsies of spiking and nonspiking hippocampal brain tissue from six patients with unilateral mesial temporal lobe epilepsy were analyzed by RNA-Seq. These profiles were correlated with transcriptomes from cell lines treated with FDA-approved drugs, identifying compounds which were tested for therapeutic efficacy in a zebrafish seizure assay. Results: In spiking versus nonspiking biopsies, RNA-Seq identified 689 differentially expressed genes, 148 of which were previously cited in articles mentioning seizures or epilepsy. Differentially expressed genes were highly enriched for protein-protein interactions and formed three clusters with associated GO-terms including myelination, protein ubiquitination, and neuronal migration. Among the 184 compounds, a zebrafish seizure model tested the therapeutic efficacy of doxycycline, metformin, nifedipine, and pyrantel tartrate, with metformin, nifedipine, and pyrantel tartrate all showing efficacy. Interpretation: This proof-of-principle analysis suggests our powerful, rapid, cost-effective approach can likely be applied to other hard-to-treat diseases.

Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals.

Differential DNA methylation in the brain is associated with many psychiatric diseases, but access to brain tissues is essentially limited to postmortem samples. The use of surrogate tissues has become common in identifying methylation changes associated with psychiatric disease. In this study, we determined the extent to which peripheral tissues can be used as surrogates for DNA methylation in the brain. Blood, saliva, buccal, and live brain tissue samples from 27 patients with medically intractable epilepsy undergoing brain resection were collected (age range 5-61 years). Genome-wide methylation was assessed with the Infinium HumanMethylation450 (n = 12) and HumanMethylationEPIC BeadChip arrays (n = 21). For the EPIC methylation data averaged for each CpG across subjects, the saliva-brain correlation (r = 0.90) was higher than that for blood-brain (r = 0.86) and buccal-brain (r = 0.85) comparisons. However, within individual CpGs, blood had the highest proportion of CpGs correlated to brain at nominally significant levels (20.8%), as compared to buccal tissue (17.4%) and saliva (15.1%). For each CpG and each gene, levels of brain-peripheral tissue correlation varied widely. This indicates that to determine the most useful surrogate tissue for representing brain DNA methylation, the patterns specific to the genomic region of interest must be considered. To assist in that objective, we have developed a website, IMAGE-CpG, that allows researchers to interrogate DNA methylation levels and degree of cross-tissue correlation in user-defined locations across the genome.

Iron nanoparticle contrast enhanced microwave imaging for emergent stroke: A pilot study.

Emergent stroke is mostly evaluated using hospital based imaging. Quick imaging allows for rapid administration of IV thrombolysis and outcome improvement. Microwave imaging (MI) is an emerging portable imaging modality. Iron oxide nanoparticles are known to interact with microwave frequency electromagnetic radiation. In this manuscript, we provide proof of concept for a novel iron oxide nanoparticle enhanced microwave imaging device for differentiating emergent ischemic stroke from hemorrhagic stroke. A MI device was constructed. Attenuation of the microwave signal transmitted with or without iron oxide nanoparticles was measured over a 1-2 GHz frequency range in a silicone brain phantom, in New Zealand white rabbits, and in a human. Observed differences in signal attenuation were used to reconstruct an image following induction of a left sided anterior circulation stroke in a New Zealand white rabbit. An increase in microwave signal attenuation exists across a frequency range of 1.3-2 GHz when iron oxide nanoparticles are introduced into a silicone phantom model, in New Zealand white rabbits, and in a human volunteer. Using this increase in signal attenuation following nanoparticle administration, we localize induced ischemia in a New Zealand white rabbit. To the best of out knowledge, we provide the first evidence that superparamagnetic Iron oxide nanoparticles may be used as contrast in the setting of MI. Our data suggest infusion of intravenous iron oxide nanoparticles with follow on microwave imaging may ultimately allow for more timely administration of thrombolytic mediation in the setting of acute ischemic stroke.

External Ventricular Drain and Hemorrhage in Aneurysmal Subarachnoid Hemorrhage Patients on Dual Antiplatelet Therapy: A Retrospective Cohort Study.

BACKGROUND: Stenting and flow diversion for aneurysmal sub arachnoid hemorrhage (aSAH) require the use of dual antiplatelet therapy (DAPT). OBJECTIVE: To investigate whether DAPT is associated with hemorrhagic complication following placement of external ventricular drains (EVD) in patients with aSAH. METHODS: Rates of radiographically identified hemorrhage associated with EVD placement were compared between patients who received DAPT for stenting or flow diversion, and patients who underwent microsurgical clipping or coiling and did not receive DAPT by way of a backward stepwise multivariate analysis. RESULTS: Four hundred forty-three patients were admitted for aSAH management. Two hundred ninety-eight patients required placement of an EVD. One hundred twenty patients (40%) were treated with stent-assisted coiling or flow diversion and required DAPT, while 178 patients (60%) were treated with coiling without stents or microsurgical clipping and did not receive DAPT. Forty-two (14%) cases of new hemorrhage along the EVD catheter were identified radiographically. Thirty-two of these hemorrhages occurred in patients on DAPT, while 10 occurred in patients without DAPT. After multivariate analysis, DAPT was significantly associated with radiographic hemorrhage [odds ratio: 4.92, 95% confidence interval: 2.45-9.91, P = .0001]. We did not observe an increased proportion of symptomatic hemorrhage in patients receiving DAPT (10 of 32 [31%]) vs those without (5 of 10 [50%]; P = .4508). CONCLUSION: Patients with aSAH who receive stent-assisted coiling or flow diversion are at higher risk for radiographic hemorrhage associated with EVD placement. The timing between EVD placement and DAPT initiation does not appear to be of clinical significance. Stenting and flow diversion remain viable options for aSAH patients.

Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging.

Background: Delirium in elderly patients is common and dangerous. Major risk factors include aging and exogenous insults, such as infection or surgery. In animal models, aging enhances pro-inflammatory cytokine release from microglia in response to exogenous insults. The epigenetic mechanism DNA methylation (DNAm) regulates gene expression and changes with age. Older individuals may have methylation changes that influence the increased cytokine upon insult, but the degree to which aging affects DNAm of cytokine genes is not fully understood. Methods: The relationship between DNAm and aging of pro-inflammatory cytokine genes (TNF-alpha, IL1-beta, IL-6) was investigated using methylation array data in two cohorts. Brain and blood samples were collected from a neurosurgery cohort (NSG) of 21 subjects who underwent brain resection. A second cohort, the Grady Trauma Project (GTP), included blood samples from 265 subjects. Results: In the NSG cohort, a significant negative correlation between age and DNAm in brain was found at a CpG in IL-6. With the GTP dataset, significant negative correlations between age and DNAm were seen at most of the CpGs in TNF-alpha. Also, TNF-Alpha expression increases with age. These GTP DNAm correlations were also nominally significant in NSG blood samples. In neuronal negative NSG brain tissue, a similar negative trend was observed. Conclusions: With aging, a decrease in DNAm of cytokines gene CpGs in glia and blood was seen. As this can affect their expression, additional research is needed to fully elucidate the role of DNAm in aging and how it may influence the pathogenesis of delirium.

Utility and safety of depth electrodes within the supratemporal plane for intracranial EEG.

OBJECTIVE: The epileptogenic zones in some patients with temporal lobe epilepsy (TLE) involve regions outside the typical extent of anterior temporal lobectomy (i.e., "temporal plus epilepsy"), including portions of the supratemporal plane (STP). Failure to identify this subset of patients and adjust the surgical plan accordingly results in suboptimum surgical outcomes. There are unique technical challenges associated with obtaining recordings from the STP. The authors sought to examine the clinical utility and safety of placing depth electrodes within the STP in patients with TLE. METHODS: This study is a retrospective review and analysis of all cases in which patients underwent intracranial electroencephalography (iEEG) with use of at least one STP depth electrode over the 10 years from January 2006 through December 2015 at University of Iowa Hospitals and Clinics. Basic clinical information was collected, including the presence of ictal auditory symptoms, electrode coverage, monitoring results, resection extent, outcomes, and complications. Additionally, cases in which the temporal lobe was primarily or secondarily involved in seizure onset and propagation were categorized based upon how rapidly epileptic activity was observed within the STP following seizure onsets: within 1 second, between 1 and 15 seconds, after 15 seconds, and not involved. RESULTS: Fifty-two patients underwent iEEG with STP coverage, with 1 STP electrode used in 45 (86.5%) cases and 2 STP electrodes in the other cases. There were no complications related to STP electrode placement. Of 42 cases in which the temporal lobe was primarily or secondarily involved, seizure activity was recorded from the STP in 36 cases (85.7%): in 5 cases (11.9%) within 1 second, in 5 (11.9%) between 1 and 15 seconds, and in 26 (61.9%) more than 15 seconds following seizure onset. Seizure outcomes inversely correlated with rapid ictal involvement of the STP (Engel class I achieved in 25%, 67%, and 82% of patients in the above categories, respectively). All patients without ictal STP involvement achieved seizure freedom. Only 4 (11.1%) patients with STP ictal involvement reported auditory symptoms. CONCLUSIONS: Ictal involvement of the STP is common even in the absence of auditory symptoms and can be effectively detected by the STP electrodes. These electrodes are safe to implant and provide useful prognostic information.

Drug-resistant epilepsy development following stem cell transplant and cyclosporine neurotoxicity induced seizures: Case report in an adult and analysis of reported cases in the literature.

INTRODUCTION: Drug-resistant epilepsy (DRE) occurs in 20-30% of all patients who develop epilepsy and can occur from diverse causes. Cyclosporine-A (CSA) is an immunosuppressive drug utilized to prevent graft-versus-host disease (GvHD) in transplant patients and is known to cause neurotoxicity, including seizures. In some cases, however, patients can develop DRE. Only a limited number of cases have been reported in which DRE has developed after CSA exposure - all in children. Here we present a rare case of an adult developing DRE after post-transplant CSA neurotoxicity. In addition, we provide a comprehensive review and analysis of all reported cases in the literature. CASE REPORT: A 29-year-old man with Non-Hodgkin's Lymphoma underwent an allogenic hematopoietic stem cell transplant and experienced a CSA-induced seizure at 7.5 months' post-transplant. The patient was discontinued on CSA and began a low dose tacrolimus regimen. At 33 months' post-transplant, he had seizure recurrence and developed DRE. Imaging revealed right mesial temporal sclerosis (MTS) and video EEG localized ictal activity to the right anterior temporal lobe. He was successfully treated with a right anterior temporal lobectomy and amygdalohippocampectomy. LITERATURE REVIEW: Seven peer-reviewed studies described 15 patients who underwent transplantation with post-transplant CSA administration and subsequently developed DRE following an initial CSA-induced seizure. All 15 patients were children suggesting that young age is a risk factor for DRE after CSA-induced seizures. Initial CSA-induced seizures occurred at an average of 1.6 ± 1.1 months after transplant and seizure recurrence 9.2 ± 8.0 months after transplant. All reported CSA routes of administration (n = 6) were intravenous and 7 of 9 (78%) reported CSA blood levels above the therapeutic range. The incidence of MTS (40%) in these 15 patients was significantly higher than the incidence in the general DRE population (24%) and was most effectively treated via epilepsy surgery. CONCLUSIONS: The use of cyclosporine for GvHD prophylaxis and treatment following transplantation may cause seizures and be associated with DRE. Although discontinuation and dose decrease of CSA often reverse adverse neurological events, initial CSA-induced seizures may be associated with MTS that and subsequent greater risk of DRE development.

Intraventricular extension of an aneurysmal subarachnoid hemorrhage is an independent predictor of a worse functional outcome.

OBJECTIVE: The objective of this study is to determine the impact of intraventricular hemorrhage (IVH) on the cognitive prognosis of subarachnoid hemorrhage (SAH) due to ruptured cerebral aneurysm, independent of the presence of intraparenchymal hemorrhage, hydrocephalus or vasospasm. PATIENT AND METHODS: A Retrospective review of a prospectively collected database of patients with aneurysmal SAH from July 2009 to November 2016 was performed. Patients were included if they had a saccular aneurysm with a Hunt-Hess grade (HHG) 1-3. Those who underwent craniectomy/clipping and those with vasospasm were excluded. Patients with IVH were grouped into 5 groups depending on the blood distribution in the ventricles. Functional outcomes studied were modified Rankin score (mRS) 0-2, cognitive impairment and memory impairment, and the presence of amnesia to the event. A univariate followed by a multivariate analysis ware performed. RESULTS: A total of 443 patients were identified and 124 patients met the criterion. There were no significant differences in the proportion of patients with mRS of 0-2 between patients with IVH and those without IVH but with EVD (external ventricular drain). There was a higher proportion of cognitive deficits in patients with IVH (71.95%), compared to those without (31.58%; p = 0.01). Patients with IVH had a higher rate of anterograde amnesia (100% vs. 4.3% p < 0.0001), lower rate of mRS 0-2 (78% vs 100% p < 0.001), and higher rate of cognitive impairment (71.9% vs. 13% p < 0.0001) compared with those who did not require an EVD. Grade 3 and grade 4 were shown to have lower rate of patients with mRS 0-2 and a higher rate of cognitive impairment. In multivariate analysis, independent predictors of cognitive and memory impairment were increasing HHG (OR = 155.33; P < 0.01), ACOM/A1/ACA/anterior choroidal aneurysms, (OR = 5.24; P = 0.04), increasing Fischer scale (OR = 6.93; P = 0.01), and increasing IVH grade (OR = 6.9; P = 0.01). Only worse HHG (OR = 2704.22; P = 0.01) and IVH grade 2-4 were associated (perfect predictor, OR cannot be extracted) with anterograde amnesia. CONCLUSION: IVH is an independent prognosticator of SAH cognitive outcomes. The effect of IVH drainage and other intraventricular therapies on SAH course is an attractive topic for further investigation.

Intracranial EEG for seizure focus localization: evolving techniques, outcomes, complications, and utility of combining surface and depth electrodes.

OBJECTIVE: Intracranial electroencephalography (iEEG) provides valuable information that guides clinical decision-making in patients undergoing epilepsy surgery, but it carries technical challenges and risks. The technical approaches used and reported rates of complications vary across institutions and evolve over time with increasing experience. In this report, the authors describe the strategy at the University of Iowa using both surface and depth electrodes and analyze outcomes and complications. METHODS: The authors performed a retrospective review and analysis of all patients who underwent craniotomy and electrode implantation from January 2006 through December 2015 at the University of Iowa Hospitals and Clinics. The basic demographic and clinical information was collected, including electrode coverage, monitoring results, outcomes, and complications. The correlations between clinically significant complications with various clinical variables were analyzed using multivariate analysis. The Fisher exact test was used to evaluate a change in the rate of complications over the study period. RESULTS: Ninety-one patients (mean age 29 ± 14 years, range 3-62 years), including 22 pediatric patients, underwent iEEG. Subdural surface (grid and/or strip) electrodes were utilized in all patients, and depth electrodes were also placed in 89 (97.8%) patients. The total number of electrode contacts placed per patient averaged 151 ± 58. The duration of invasive monitoring averaged 12.0 ± 5.1 days. In 84 (92.3%) patients, a seizure focus was localized by ictal onset (82 cases) or inferred based on interictal discharges (2 patients). Localization was achieved based on data obtained from surface electrodes alone (29 patients), depth electrodes alone (13 patients), or a combination of both surface and depth electrodes (42 patients). Seventy-two (79.1%) patients ultimately underwent resective surgery. Forty-seven (65.3%) and 18 (25.0%) patients achieved modified Engel class I and II outcomes, respectively. The mean follow-up duration was 3.9 ± 2.9 (range 0.1-10.5) years. Clinically significant complications occurred in 8 patients, including hematoma in 3 (3.3%) patients, infection/osteomyelitis in 3 (3.3%) patients, and edema/compression in 2 (2.2%) patients. One patient developed a permanent neurological deficit (1.1%), and there were no deaths. The hemorrhagic and edema/compression complications correlated significantly with the total number of electrode contacts (p = 0.01), but not with age, a history of prior cranial surgery, laterality, monitoring duration, and the number of each electrode type. The small number of infectious complications precluded multivariate analysis. The number of complications decreased from 5 of 36 cases (13.9%) to 3 of 55 cases (5.5%) during the first and last 5 years, respectively, but this change was not statistically significant (p = 0.26). CONCLUSIONS: An iEEG implantation strategy that makes use of both surface and depth electrodes is safe and effective at identifying seizure foci in patients with medically refractory epilepsy. With experience and iterative refinement of technical surgical details, the risk of complications has decreased over time.

Detection of microbleeds associated with sentinel headache using MRI quantitative susceptibility mapping: pilot study.

OBJECT: Sentinel headaches (SHs) associated with cerebral aneurysms (CAs) could be due to microbleeds, which are considered a sign that an aneurysm is unstable. Despite the prognostic importance of these microbleeds, they remain difficult to detect using routine imaging studies. The objective of this pilot study is to detect microbleeds associated with SH using a magnetic resonance imaging (MRI) quantitative susceptibility mapping (QSM) sequence and then evaluate the morphological characteristics of unstable aneurysms with microbleeds. METHODS: Twenty CAs in 16 consecutive patients with an initial presentation of headache (HA) leading to a diagnosis of CA were analyzed. Headaches in 4 of the patients (two of whom had 2 aneurysms each) met the typical definition of SH, and the other 12 patients (two of whom also had 2 aneurysms each) all had migraine HA. All patients underwent imaging with the MRI-QSM sequence. Two independent MRI experts who were blinded to the patients' clinical history performed 3D graphical analysis to evaluate for potential microbleeds associated with these CAs. Computational flow and morphometric analyses were also performed to estimate wall shear and morphological variables. RESULTS: In the 4 patients with SH, MRI-QSM results were positive for 4 aneurysms, and hence these aneurysms were considered positive for non-heme ferric iron (microbleeds). The other 16 aneurysms were negative. Among aneurysm shape indices, the undulation index was significantly higher in the QSM-positive group than in the QSM-negative group. In addition, the spatial averaged wall shear magnitude was lower in the aneurysm wall in direct contact with microbleeds. CONCLUSIONS: MRI-QSM allows for objective detection of microbleeds associated with SH and therefore identification of unstable CAs. CAs with slightly greater undulation indices are associated with positive MRI-QSM results and hence with microbleeds. Studies with larger populations are needed to confirm these preliminary findings.

Accuracy of detecting enlargement of aneurysms using different MRI modalities and measurement protocols.

OBJECTIVE: Aneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical MRI is still unknown. The purpose of this study was to assess the agreement rate of detecting aneurysm enlargement employing generally used MRI modalities. METHODS: Three silicone flow phantom models, each with 8 aneurysms of various sizes at different sites, were used in this study. The aneurysm models were identical except for an incremental increase in the sizes of the 8 aneurysms, which ranged from 0.4 mm to 2 mm. The phantoms were imaged on 1.5-T and 3-T MRI units with both time-of-flight (TOF) and contrast-enhanced MR angiography. Three independent expert neuroradiologists measured the aneurysms in a blinded manner using different measurement approaches. The individual and agreement detection rates of aneurysm enlargement among the 3 experts were calculated. RESULTS: The mean detection rate of any increase in any aneurysmal dimension was 95.7%. The detection rates of the 3 observers (observers A, B, and C) were 98.0%, 96.6%, and 92.7%, respectively (p = 0.22). The detection rates of each MRI modality were 91.3% using 1.5-T TOF, 97.2% using 1.5-T with Gd, 95.8% using 3.0-T TOF, and 97.2% using 3.0-T with Gd (p = 0.31). On the other hand, the mean detection rate for aneurysm enlargement was 54.8%. Specifically, the detection rates of observers A, B, and C were 49.0%, 46.1%, and 66.7%, respectively (p = 0.009). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. The use of 1.5-T Gd improved the detection rate for small incremental enlargement (e.g., 0.4­1 mm) of the aneurysm (p = 0.04). The location of the aneurysm also affected the detection rate for aneurysm enlargement (p < 0.0001). CONCLUSIONS: The detection rate and interobserver agreement were very high for aneurysm enlargement of 0.4­2 mm. The detection rate for at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or measurement protocol. Use of Gd improved the accuracy of measurement. Aneurysm location may influence the accuracy of detecting enlargement.

Deep brain stimulation hardware-related infections: 10-year experience at a single institution.

OBJECTIVEDeep brain stimulation is an effective surgical treatment for managing some neurological and psychiatric disorders. Infection related to the deep brain stimulator (DBS) hardware causes significant morbidity: hardware explantation may be required; initial disease symptoms such as tremor, rigidity, and bradykinesia may recur; and the medication requirements for adequate disease management may increase. These morbidities are of particular concern given that published DBS-related infection rates have been as high as 23%. To date, however, the key risk factors for and the potential preventive measures against these infections remain largely uncharacterized. In this study, the authors endeavored to identify possible risk factors for DBS-related infection and analyze the efficacy of prophylactic intrawound vancomycin powder (VP).METHODSThe authors performed a retrospective cohort study of patients who had undergone primary DBS implantation at a single institution in the period from December 2005 through September 2015 to identify possible risk factors for surgical site infection (SSI) and to assess the impact of perioperative (before, during, and after surgery) prophylactic antibiotics on the SSI rate. They also evaluated the effect of a change in the National Healthcare Safety Network's definition of SSI on the number of infections detected. Statistical analyses were performed using the 2-sample t-test, the Wilcoxon rank-sum test, the chi-square test, Fisher's exact test, or logistic regression, as appropriate for the variables examined.RESULTSFour hundred sixty-four electrodes were placed in 242 adults during 245 primary procedures over approximately 10.5 years; most patients underwent bilateral electrode implantation. Among the 245 procedures, 9 SSIs (3.7%) occurred within 90 days and 16 (6.5%) occurred within 1 year of DBS placement. Gram-positive bacteria were the most common etiological agents. Most patient- and procedure-related characteristics did not differ between those who had acquired an SSI and those who had not. The rate of SSIs among patients who had received intrawound VP was only 3.3% compared with 9.7% among those who had not received topical VP (OR 0.32, 95% CI 0.10-1.02, p = 0.04). After controlling for patient sex, the association between VP and decreased SSI risk did not reach the predetermined level of significance (adjusted OR 0.32, 95% CI 0.10-1.03, p = 0.06). The SSI rates were similar after staged and unstaged implantations.CONCLUSIONSWhile most patient-related and procedure-related factors assessed in this study were not associated with the risk for an SSI, the data did suggest that intrawound VP may help to reduce the SSI risk after DBS implantation. Furthermore, given the implications of SSI after DBS surgery and the frequency of infections occurring more than 90 days after implantation, continued follow-up for at least 1 year after such a procedure is prudent to establish the true burden of these infections and to properly treat them when they do occur.