Publications by authors named "Ashwini D Sharan"

100 Publications

Consequences of mesial temporal sparing temporal lobe surgery in medically refractory epilepsy.

Epilepsy Behav 2021 Feb 23;115:107642. Epub 2020 Dec 23.

Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, Philadelphia, PA, United States; Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States.

Objective: We compared long-term seizure outcome, neuropsychological outcome, and occupational outcome of anterior temporal lobectomy (ATL) with and without sparing of mesial structures to determine whether mesial sparing temporal lobectomy prevents memory decline and thus disability, with acceptable seizure outcome.

Methods: We studied patients (n = 21) and controls (n = 21) with no evidence of mesial temporal sclerosis (MTS) on MRI who had surgery to treat drug-resistant epilepsy. Demographic and pre- and postsurgical clinical characteristics were compared. Patients had neuropsychological assessment before and after surgery. Neuropsychological analyses were limited to patients with left-sided surgery and available data (n = 14 in each group) as they were at risk of verbal memory impairment. The California Verbal Learning Test II (CVLT-II) (sum of trials 1-5, delayed free recall) and the Logical Memory subtest of the Wechsler Memory Scale III or IV (WMS-III or WMS-IV) (learning and delayed recall of prose passages) were used to assess verbal episodic learning and memory. Seizure and occupational outcomes were assessed.

Results: The chance of attaining seizure freedom was similar in the two groups, so sparing mesial temporal structures did not lessen the chance of stopping seizures. Sparing mesial temporal structures mitigated the extent of postoperative verbal memory impairment, though some of these individuals suffered decline as a consequence of surgery. Occupational outcome was similar in both groups.

Significance: Mesial temporal sparing resections provide a similar seizure outcome as ATL, while producing a better memory outcome. Anterior temporal lobectomy including mesial structure resection did not increase the risk of postoperative disability.
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http://dx.doi.org/10.1016/j.yebeh.2020.107642DOI Listing
February 2021

Contribution of left supramarginal and angular gyri to episodic memory encoding: An intracranial EEG study.

Neuroimage 2021 01 1;225:117514. Epub 2020 Nov 1.

Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, United States.

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs). Furthermore, few studies have compared the relative contributions of sub-regions in this functionally heterogeneous area, specifically the anterior VPC (supramarginal gyrus/BA40) and the posterior VPC (angular gyrus/BA39), on a within-subject basis. To elucidate the role of the VPC in episodic encoding, we compared SMEs in the intracranial EEG across multiple frequency bands in the supramarginal gyrus (SmG) and angular gyrus (AnG), as twenty-four epilepsy patients with indwelling electrodes performed a free recall task. We found a significant SME of decreased theta power and increased high gamma power in the VPC overall, and specifically in the SmG. Furthermore, SmG exhibited significantly greater spectral tilt SME from 0.5 to 1.6 s post-stimulus, in which power spectra slope differences between recalled and unrecalled words were greater than in the AnG (p = 0.04). These results affirm the contribution of VPC to episodic memory encoding, and suggest an anterior-posterior dissociation within VPC with respect to its electrophysiological underpinnings.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117514DOI Listing
January 2021

Developing standardized titles to classify the adverse events in 7,418 cranial and spinal neurosurgical procedures.

Clin Neurol Neurosurg 2020 Nov 1;198:106121. Epub 2020 Aug 1.

Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA. Electronic address:

Background: Neurosurgical procedures are life- and function-saving but carry a risk of adverse events (AE) which can cause permanent neurologic deficits. Unfortunately, there is lack of clearly defined AEs associated with given procedures, and their reporting is non-uniform and often arbitrary. However, with an increasing number of neurosurgical procedures performed, there is a need for standardization of AEs for systematic tracking. Such a system would establish a baseline for future quality improvement strategies.

Objective: To review our institutional AEs and devise standardized titles specific to the spine, tumor, functional, and vascular neurosurgery divisions.

Methods: A review of prospective monthly-reported morbidity and mortality (M&M) conference data within the Department of Neurological Surgery was conducted from January 2017 to December 2019. An AE was defined as any mortality, an "unintended and undesirable diagnostic or therapeutic event", "an event that prolongs the patient's hospital stay", or an outcome with permanent or transient neurologic deficit.

Results: A total of 1096 AEs from 7418 total procedures (14.8 %) were identified. Of those, 418 (5.6 %) were in cerebrovascular, 249 (3.4 %) were in neuro-oncology and 429 (5.8 %) were in the spine & functional divisions. The most common AEs across all divisions were infection (17 %), hemorrhage (11 %) and cerebrospinal fluid (CSF) leak (7.8 %). Other AEs were indirectly related to the neurosurgical procedure, such as deep vein thrombosis or pulmonary embolism (2.7 %), or pneumothorax (0.3 %).

Conclusion: This work illustrates standardized AEs can be implemented universally across the spectrum of neurological surgery. Standardization can help identify recurring AE patterns through better tracking.
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http://dx.doi.org/10.1016/j.clineuro.2020.106121DOI Listing
November 2020

Predictors of 30-day hospital readmission after mechanical thrombectomy for acute ischemic stroke.

J Neurosurg 2020 May 1:1-5. Epub 2020 May 1.

1Department of Neurological Surgery, Thomas Jefferson University and Jefferson Hospital for Neuroscience; and.

Objective: The 30-day readmission rate is of increasing interest to hospital administrators and physicians, as it is used to evaluate hospital performance and is associated with increased healthcare expenditures. The estimated yearly cost to Medicare of readmissions is $17.4 billion. The Centers for Medicare and Medicaid Services therefore track unplanned 30-day readmissions and institute penalties against hospitals whose readmission rates exceed disease-specific national standards. One of the most important conditions with potential for improvement in cost-effective care is ischemic stroke, which affects 795,000 people in the United States and is a leading cause of death and disability. Recent widespread adoption of mechanical thrombectomy has revolutionized stroke care, requiring reassessment of readmission causes and costs in this population.

Methods: The authors retrospectively analyzed a prospectively maintained database of stroke patients and identified 561 patients who underwent mechanical thrombectomy between 2010 and 2019 at the authors' institution. Univariate and multivariate analyses were conducted to identify clinical variables and comorbidities related to 30-day readmissions in this patient population.

Results: Of the 561 patients, 85.6% (n = 480) survived their admission and were discharged from the hospital to home or rehabilitation, and 8.8% (n = 42/480) were readmitted within 30 days. The median time to readmission was 10.5 days (IQR 6.0-14.3). The most common reasons for readmission were infection (33.3%) and acute cardiac or cerebrovascular events (19% and 20%, respectively). Multivariate analysis showed that hypertension (p = 0.030; OR 2.72) and length of initial hospital stay (p = 0.040; OR 1.032) were significantly correlated with readmission within 30 days, while hemorrhagic conversion (grades 3 and 4) approached significance (p = 0.053; OR 2.23). Other factors, such as unfavorable outcome at discharge, history of coronary artery disease, and discharge destination, did not predict readmission.

Conclusions: The study data demonstrate that hypertension, length of hospital stay, and hemorrhagic conversion were predictors of 30-day hospital readmission in stroke patients after mechanical thrombectomy. Infection was the most common cause of 30-day readmission, followed by cardiac and cerebrovascular diagnoses. These results therefore may serve to identify patients within the stroke population who require increased surveillance following discharge to reduce complications and unplanned readmissions.
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http://dx.doi.org/10.3171/2020.2.JNS193249DOI Listing
May 2020

Letter to the Editor: "Bridging Machine Learning and Clinical Practice in Neurosurgery: Hurdles and Solutions".

World Neurosurg 2020 02;134:678-679

Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

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http://dx.doi.org/10.1016/j.wneu.2019.11.105DOI Listing
February 2020

Reactivated Spatial Context Guides Episodic Recall.

J Neurosci 2020 03 23;40(10):2119-2128. Epub 2020 Jan 23.

Computational Memory Laboratory, Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104,

The medial temporal lobe (MTL) is known as the locus of spatial coding and episodic memory, but the interaction between these cognitive domains as well as the extent to which they rely on common neurophysiological mechanisms is poorly understood. Here, we use intracranial electroencephalography and a hybrid spatial-episodic memory task (29 subjects, 15 female) to determine how spatial information is dynamically reactivated in subregions of the human MTL and how this reactivation guides recall of episodic information. Our results implicate theta oscillations across the MTL as a common neurophysiological substrate for spatial coding in navigation and episodic recall. We further show that our index of retrieved spatial context is high in the hippocampus (HC) in an early time window preceding recall. Closer to recall, it decreases in the HC and increases in the parahippocampal gyrus. Finally, we demonstrate that hippocampal theta phase modulates parahippocampal gamma amplitude during retrieval of spatial context, suggesting a role for cross-frequency coupling in coding and transmitting retrieved spatial information. By recording from the human medial temporal lobe (MTL) while subjects recall items experienced in a virtual environment, we establish a direct relation between the strength of theta activity during memory search and the extent to which memories are organized by their spatial locations. We thereby pinpoint a role for theta oscillations in accessing the "cognitive map" during episodic retrieval and further highlight the dynamic interplay of hippocampus and extrahippocampal MTL in representing retrieved spatial context. Our results provide an important step toward a unified theory of MTL function encompassing its role in spatial navigation and episodic memory.
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http://dx.doi.org/10.1523/JNEUROSCI.1640-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055128PMC
March 2020

Clinically Significant Visual Deficits after Laser Interstitial Thermal Therapy for Mesiotemporal Epilepsy.

Stereotact Funct Neurosurg 2019 14;97(5-6):347-355. Epub 2020 Jan 14.

Department of Neurological Surgery, University of Miami, Miami, Florida, USA,

Background: Laser interstitial thermal therapy (LITT) has recently gained popularity as a minimally invasive surgical option for the treatment of mesiotemporal epilepsy (mTLE). Similar to traditional open procedures for epilepsy, the most frequent neurological complications of LITT are visual deficits; however, a critical analysis of these injuries is lacking.

Objectives: To evaluate the visual deficits that occur after LITT for mTLE and their etiology.

Method: We surveyed five academic epilepsy centers that regularly perform LITT for cases of self-reported postoperative visual deficits. For these patients all pre-, intra- and postoperative MRIs were co-registered with an anatomic atlas derived from 7T MRI data. This was used to estimate thermal injury to early visual pathways and measure imaging variables relevant to the LITT procedure. Using logistic regression, we then compared 14 variables derived from demographics, mesiotemporal anatomy, and the surgical procedure for the patients with visual deficits to a normal cohort comprised of the first 30 patients to undergo this procedure at a single institution.

Results: Of 90 patients that underwent LITT for mTLE, 6 (6.7%) reported a postoperative visual deficit. These included 2 homonymous hemianopsias (HHs), 2 quadrantanopsias, and 2 cranial nerve (CN) IV palsies. These deficits localized to the posterior aspect of the ablation, corresponding to the hippocampal body and tail, and tended to have greater laser energy delivered in that region than the normal cohort. The patients with HH had insult localized to the lateral geniculate nucleus, which was -associated with young age and low choroidal fissure CSF volume. Quadrantanopsia, likely from injury to the optic radiation in Meyer's loop, was correlated with a lateral trajectory and excessive energy delivered at the tail end of the ablation. Patients with CN IV injury had extension of contrast to the tentorial edge associated with a mesial laser trajectory.

Conclusions: LITT for epilepsy may be complicated by various classes of visual deficit, each with distinct etiology and clinical significance. It is our hope that by better understanding these injuries and their mechanisms we can eventually reduce their occurrence by identifying at-risk patients and trajectories and appropriately tailoring the ablation procedure.
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http://dx.doi.org/10.1159/000504856DOI Listing
June 2020

Officers of the Congress of Neurological Surgeons 2018.

Authors:
Ashwini D Sharan

Neurosurgery 2019 09;66(Suppl 1):N3

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http://dx.doi.org/10.1093/neuros/nyz329DOI Listing
September 2019

What is Mission: Neurosurgery, 2018.

Authors:
Ashwini D Sharan

Neurosurgery 2019 09;66(Suppl 1):1-12

Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1093/neuros/nyz255DOI Listing
September 2019

Implantable Pulse Generator Site May Be Associated With Spinal Cord Stimulation Revision Surgeries.

Neuromodulation 2019 Jun 19. Epub 2019 Jun 19.

Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA.

Background: The use of implantable pulse generators (IPG) for spinal cord stimulation (SCS) in patients with chronic pain has been well established. Although IPG-related complications have been reported on, the association between IPG site and SCS complications has not been well studied.

Objective: To investigate whether IPG placement site in buttock or flank is associated with SCS complications and, hence, revision surgeries.

Method: A retrospective cohort study was performed that included 330 patients (52% female) treated at a single institution who underwent permanent implantation of an SCS system between 2014 and 2018. Patients ranged between 20 and 94 years of age (mean: 57.54 ± 13.25). Statistical analyses were conducted using IBM SPSS Statistics. Tests included independent samples t test, chi-square test, Mann-Whitney U test, Spearman's rank correlation coefficient, and logistic regression.

Results: There was a total of 93 revision surgeries (rate of 28%), where 71 out of 330 patients (rate of 21.5%) had had at least one revision surgery. Univariate tests demonstrated a significant association between IPG site and revision surgeries (p = 0.028 [chi-square test] and p = 0.031 [Mann-Whitney U test]); however, multivariate logistic regression demonstrated that neither IPG site was more likely than the other to require revision surgeries (p = 0.286).

Conclusion: Although this study found a significant association between IPG site and revision surgeries, the effect of IPG site was not found to be predictive. The IPG site likely influences whether a patient will require revision surgery, but further investigation is required to establish this association.
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http://dx.doi.org/10.1111/ner.12976DOI Listing
June 2019

Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients.

Epilepsia 2019 06 21;60(6):1171-1183. Epub 2019 May 21.

Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, Tennessee.

Objective: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow-up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three-dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image-based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE.

Methods: This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively.

Results: Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic-clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome.

Significance: LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.
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http://dx.doi.org/10.1111/epi.15565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551254PMC
June 2019

First-in-human implantation of a mid-field powered neurostimulator at the sacral nerve: Results from an acute study.

Neurourol Urodyn 2019 08 20;38(6):1669-1675. Epub 2019 May 20.

Department of Urology and Obstetrics and Gynecology, Stanford University Medical Center, Stanford, California.

Introduction: Commercially approved implantable systems for sacral neuromodulation require the implantation of a multipolar lead subcutaneously connected to an implantable pulse generator (IPG). Eliminating the need for an IPG would eliminate the need for tunneling of the lead, reduce procedure time, infection risk, and the need for IPG replacement. The objective was to demonstrate the feasibility of implanting the AHLeveeS System in the S3 Foramen to stimulate the S3 sacral nerve.

Materials And Methods: A first-in-human, prospective, single center, nonrandomized, acute feasibility clinical investigation at the Maastricht University Medical Center+. Patients with refractory overactive bladder underwent acute implantation of the AHLeveeS neurostimulator before the InterStim procedure. Outcome measurements included motor responses, procedural time and a scoring of the difficulty of the implant and explant procedure. Retrospectively, qualitative responses to the stimulation protocol were assessed by video motion analyses. Only descriptive statistics were used.

Results: During the stimulation a motor response to stimulation was seen in four of the five subjects. In all implantations the AHLeveeS was correctly placed. The median time for complete procedure was 24 minutes. The implant and explant procedures were successfully performed and no device or procedure related adverse events occurred.

Conclusions: The results from this acute first-in-human study demonstrate the feasibility of implantation and acute stimulation of the sacral nerve with this mid-field powered system. Future clinical studies will focus on safety and efficacy of a chronically implanted device.
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http://dx.doi.org/10.1002/nau.24035DOI Listing
August 2019

Sphenopalatine ganglion stimulation is a reversible and frequency-dependent modulator of the blood-brain barrier.

Brain Res 2019 09 26;1718:231-241. Epub 2019 Apr 26.

Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA, USA.

Background: The sphenopalatine ganglion (SPG) is a vasoactive mediator of the anterior intracranial circulation in mammals. SPG stimulation has been demonstrated to alter blood-brain barrier (BBB) permeability, although this phenomenon is not well characterized.

Objective: To determine the effect of SPG stimulation on the BBB using rat models.

Methods: Extravasation of fluorescent tracer 70 kDa FITC-dextran into rat brain specimens was measured across a range of stimulation parameters to assess BBB permeability. Tight junction (TJ) morphology was compared by assessing differences in the staining of proteins occludin and ZO-1 and analyzing ultrastructural changes on transmission electron microscopy (TEM) between stimulated and unstimulated specimens.

Results: SPG stimulation at 10 Hz maximally increased BBB permeability, exhibiting a 6-fold increase in fluorescent traceruptake (1.66% vs 0.28%, p < 0.0001). This effect was reversed 4-hours after stimulation (0.36% uptake, p = 0.99). High-frequency stimulation at 20 Hz and 200 Hz did not increase tracer extravasation, (0.26% and 0.28% uptake, p = >0.999 and p = 0.998, respectively). Stimulation was associated a significant decrease in the colocalization of occludin and ZO-1 with endothelial markers in stimulated brains compared to control (74.6% vs. 39.7% and 67.2% vs. 60.4% colocalization, respectively, p < 0.0001), and ultrastructural changes in TJ morphology associated with increased BBB permeability were observed on TEM.

Conclusion: This study is the first to show a reversible, frequency-dependent increase in BBB permeability with SPG stimulation and introduces a putative mechanism of action through TJ disruption. Bypassing the BBB with SPG stimulation could enable new paradigms in delivering therapeutics to the CNS. Further study of this technology is needed.
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http://dx.doi.org/10.1016/j.brainres.2019.04.030DOI Listing
September 2019

Association of Piriform Cortex Resection With Surgical Outcomes in Patients With Temporal Lobe Epilepsy.

JAMA Neurol 2019 06;76(6):690-700

UK National Institute for Health Research, University College London (UCL) Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, United Kingdom.

Importance: A functional area associated with the piriform cortex, termed area tempestas, has been implicated in animal studies as having a crucial role in modulating seizures, but similar evidence is limited in humans.

Objective: To assess whether removal of the piriform cortex is associated with postoperative seizure freedom in patients with temporal lobe epilepsy (TLE) as a proof-of-concept for the relevance of this area in human TLE.

Design, Setting, And Participants: This cohort study used voxel-based morphometry and volumetry to assess differences in structural magnetic resonance imaging (MRI) scans in consecutive patients with TLE who underwent epilepsy surgery in a single center from January 1, 2005, through December 31, 2013. Participants underwent presurgical and postsurgical structural MRI and had at least 2 years of postoperative follow-up (median, 5 years; range, 2-11 years). Patients with MRI of insufficient quality were excluded. Findings were validated in 2 independent cohorts from tertiary epilepsy surgery centers. Study follow-up was completed on September 23, 2016, and data were analyzed from September 24, 2016, through April 24, 2018.

Exposures: Standard anterior temporal lobe resection.

Main Outcomes And Measures: Long-term postoperative seizure freedom.

Results: In total, 107 patients with unilateral TLE (left-sided in 68; 63.6% women; median age, 37 years [interquartile range {IQR}, 30-45 years]) were included in the derivation cohort. Reduced postsurgical gray matter volumes were found in the ipsilateral piriform cortex in the postoperative seizure-free group (n = 46) compared with the non-seizure-free group (n = 61). A larger proportion of the piriform cortex was resected in the seizure-free compared with the non-seizure-free groups (median, 83% [IQR, 64%-91%] vs 52% [IQR, 32%-70%]; P < .001). The results were seen in left- and right-sided TLE and after adjusting for clinical variables, presurgical gray matter alterations, presurgical hippocampal volumes, and the proportion of white matter tract disconnection. Findings were externally validated in 2 independent cohorts (31 patients; left-sided TLE in 14; 54.8% women; median age, 41 years [IQR, 31-46 years]). The resected proportion of the piriform cortex was individually associated with seizure outcome after surgery (derivation cohort area under the curve, 0.80 [P < .001]; external validation cohorts area under the curve, 0.89 [P < .001]). Removal of at least half of the piriform cortex increased the odds of becoming seizure free by a factor of 16 (95% CI, 5-47; P < .001). Other mesiotemporal structures (ie, hippocampus, amygdala, and entorhinal cortex) and the overall resection volume were not associated with outcomes.

Conclusions And Relevance: These results support the importance of resecting the piriform cortex in neurosurgical treatment of TLE and suggest that this area has a key role in seizure generation.
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http://dx.doi.org/10.1001/jamaneurol.2019.0204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490233PMC
June 2019

Neural activity reveals interactions between episodic and semantic memory systems during retrieval.

J Exp Psychol Gen 2019 Jan;148(1):1-12

Department of Psychology, University of Pennsylvania.

Whereas numerous findings support a distinction between episodic and semantic memory, it is now widely acknowledged that these two forms of memory interact during both encoding and retrieval. The precise nature of this interaction, however, remains poorly understood. To examine the role of semantic organization during episodic encoding and retrieval, we recorded intracranial encephalographic signals as 69 neurosurgical patients studied and subsequently recalled categorized and unrelated word lists. Applying multivariate classifiers to neural recordings, we were able to reliably predict encoding success, retrieval success, and temporal and categorical clustering during recall. By assessing how these classifiers generalized across list types, we identified specific retrieval processes that predicted recall of categorized lists and distinguished between recall transitions within and between category clusters. These results particularly implicate retrieval (rather than encoding) processes in the categorical organization of episodic memories. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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http://dx.doi.org/10.1037/xge0000480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419095PMC
January 2019

Ripple oscillations in the left temporal neocortex are associated with impaired verbal episodic memory encoding.

Epilepsy Behav 2018 11 11;88:33-40. Epub 2018 Sep 11.

Dept. of Neurology and Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address:

Background: We sought to determine if ripple oscillations (80-120 Hz), detected in intracranial electroencephalogram (iEEG) recordings of patients with epilepsy, correlate with an enhancement or disruption of verbal episodic memory encoding.

Methods: We defined ripple and spike events in depth iEEG recordings during list learning in 107 patients with focal epilepsy. We used logistic regression models (LRMs) to investigate the relationship between the occurrence of ripple and spike events during word presentation and the odds of successful word recall following a distractor epoch and included the seizure onset zone (SOZ) as a covariate in the LRMs.

Results: We detected events during 58,312 word presentation trials from 7630 unique electrode sites. The probability of ripple on spike (RonS) events was increased in the SOZ (p < 0.04). In the left temporal neocortex, RonS events during word presentation corresponded with a decrease in the odds ratio (OR) of successful recall, however, this effect only met significance in the SOZ (OR of word recall: 0.71, 95% confidence interval (CI): 0.59-0.85, n = 158 events, adaptive Hochberg, p < 0.01). Ripple on oscillation (RonO) events that occurred in the left temporal neocortex non-SOZ also correlated with decreased odds of successful recall (OR: 0.52, 95% CI: 0.34-0.80, n = 140, adaptive Hochberg, p < 0.01). Spikes and RonS that occurred during word presentation in the left middle temporal gyrus (MTG) correlated with the most significant decrease in the odds of successful recall, irrespective of the location of the SOZ (adaptive Hochberg, p < 0.01).

Conclusion: Ripples and spikes generated in the left temporal neocortex are associated with impaired verbal episodic memory encoding. Although physiological and pathological ripple oscillations were not distinguished during cognitive tasks, our results show an association of undifferentiated ripples with impaired encoding. The effect was sometimes specific to regions outside the SOZ, suggesting that widespread effects of epilepsy outside the SOZ may contribute to cognitive impairment.
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http://dx.doi.org/10.1016/j.yebeh.2018.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240385PMC
November 2018

A Novel Technique for Prevention of Subarachnoid-Pleural Fistula After Incidental Durotomy During Transthoracic Spinal Surgery.

Oper Neurosurg (Hagerstown) 2019 04;16(4):451-454

Department of Neuro-surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

Background: Subarachnoid-pleural fistulas (SPFs) are rare but significant complications of transthoracic spinal surgery. Whether noted intraoperatively or in the postoperative period, SPF requires implementation of aggressive management, with consideration given to direct surgical repair. Additionally, the physical constraints of the thoracic cavity often hinder direct SPF repair.

Objective: To present a novel operative technique that can be used to easily and quickly address incidental durotomy incurred during transthoracic spinal surgery while working within the confines of the thorax.

Methods: Surgical hemostatic clips were used to affix a patch-graft of dural substitute to the parietal pleura surrounding the site of a transthoracic spinal decompression in which an incidental durotomy was incurred. The patch-graft was augmented with the application of biological glue and was successful in preventing symptomatic SPF.

Results: The use of surgical clips to affix a patch graft is a quick, easy, and effective means of addressing an incidental durotomy during thoracotomy and preventing SPF. The clip applier is significantly easier to maneuver within the narrow working channel of the thorax than are instruments used during direct repair.

Conclusion: Preventing SPF can be challenging. The physical constraints of the thoracic cavity make water-tight repair difficult and time-consuming, particularly when the morphology of the dural tear prevents primary apposition of the defect. The authors present a novel technique of preventing development of SPF using hemostatic clips to simply and quickly affix suturable dural substitute to the parietal pleura overlying the site of an incidental durotomy.
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http://dx.doi.org/10.1093/ons/opy170DOI Listing
April 2019

Commentary: The Future Currency of Neurosurgery is Data.

Neurosurgery 2018 09;83(3):E125-E127

Department of Neurosurgery, Jacobs School of Medicine, University at Buffalo, Buffalo, New York.

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http://dx.doi.org/10.1093/neuros/nyy259DOI Listing
September 2018

Influences of temporal lobe epilepsy and temporal lobe resection on olfaction.

J Neurol 2018 Jul 16;265(7):1654-1665. Epub 2018 May 16.

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring  the tests' associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study.
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http://dx.doi.org/10.1007/s00415-018-8891-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239967PMC
July 2018

Task activation and functional connectivity show concordant memory laterality in temporal lobe epilepsy.

Epilepsy Behav 2018 04 20;81:70-78. Epub 2018 Mar 20.

Thomas Jefferson University, Department of Neurology, United States. Electronic address:

Objective: In epilepsy, asymmetries in the organization of mesial temporal lobe (MTL) functions help determine the cognitive risk associated with procedures such as anterior temporal lobectomy. Past studies have investigated the change/shift in a visual episodic memory laterality index (LI) in mesial temporal lobe structures through functional magnetic resonance imaging (fMRI) task activations. Here, we examine whether underlying task-related functional connectivity (FC) is concordant with such standard fMRI laterality measures.

Methods: A total of 56 patients with temporal lobe epilepsy (TLE) (Left TLE [LTLE]: 31; Right TLE [RTLE]: 25) and 34 matched healthy controls (HC) underwent fMRI scanning during performance of a scene encoding task (SET). We assessed an activation-based LI of the hippocampal gyrus (HG) and parahippocampal gyrus (PHG) during the SET and its correspondence with task-related FC measures.

Results: Analyses involving the HG and PHG showed that the patients with LTLE had a consistently higher LI (right-lateralized) than that of the HC and group with RTLE, indicating functional reorganization. The patients with RTLE did not display a reliable contralateral shift away from the pathology, with the mesial structures showing quite distinct laterality patterns (HG, no laterality bias; PHG, no evidence of LI shift). The FC data for the group with LTLE provided confirmation of reorganization effects, revealing that a rightward task LI may be based on underlying connections between several left-sided regions (middle/superior occipital and left medial frontal gyri) and the right PHG. The FCs between the right HG and left anterior cingulate/medial frontal gyri were also observed in LTLE. Importantly, the data demonstrate that the areas involved in the LTLE task activation shift to the right hemisphere showed a corresponding increase in task-related FCs between the hemispheres.

Significance: Altered laterality patterns based on mesial temporal lobe epilepsy (MTLE) pathology manifest as several different phenotypes, varying according to side of seizure onset and the specific mesial structures involved. There is good correspondence between task LI activation and FC patterns in the setting of LTLE, suggesting that reliable visual episodic memory reorganization may require both a shift in nodal activation and a change in nodal connectivity with mesial temporal structures involved in memory.
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http://dx.doi.org/10.1016/j.yebeh.2018.01.027DOI Listing
April 2018

Increased neuronal synchrony prepares mesial temporal networks for seizures of neocortical origin.

Epilepsia 2018 03 14;59(3):636-649. Epub 2018 Feb 14.

School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA.

Objective: To gain understanding of the neuronal mechanisms underlying regional seizure spread, the impact of regional synchrony between seizure focus and downstream networks on neuronal activity during the transition to seizure in those downstream networks was assessed.

Methods: Seven patients undergoing diagnostic intracranial electroencephalographic studies for surgical resection of epileptogenic regions were implanted with subdural clinical electrodes into the cortex (site of seizure initiation) and mesial temporal lobe (MTL) structures (downstream) as well as microwires into MTL. Neural activity was recorded (24/7) in parallel with the clinical intracranial electroencephalogram recordings for the duration of the patient's diagnostic stay. Changes in (1) regional synchrony (ie, coherence) between the presumptive neocortical seizure focus and MTL, (2) local synchrony between MTL neurons and their local field potential, and (3) neuronal firing rates within MTL in the time leading up to seizure were examined to study the mechanisms underlying seizure spread.

Results: In seizures of neocortical origin, an increase in regional synchrony preceded the spread of seizures into MTL (predominantly hippocampal). Within frequencies similar to those of regional synchrony, MTL networks showed an increase in unit-field coherence and a decrease in neuronal firing rate, specifically for inhibitory interneuron populations but not pyramidal cell populations.

Significance: These results suggest a mechanism of spreading seizures whereby the seizure focus first synchronizes local field potentials in downstream networks to the seizure activity. This change in local field coherence modifies the activity of interneuron populations in these downstream networks, which leads to the attenuation of interneuronal firing rate, effectively shutting down local interneuron populations prior to the spread of seizure. Therefore, regional synchrony may influence the failure of downstream interneurons to prevent the spread of the seizures during generalization.
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http://dx.doi.org/10.1111/epi.14007DOI Listing
March 2018

Closed-loop stimulation of temporal cortex rescues functional networks and improves memory.

Nat Commun 2018 02 6;9(1):365. Epub 2018 Feb 6.

Department of Psychology, University of Pennsylvania, 433 South University Avenue, Philadelphia, PA, 19104, USA.

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target for memory enhancement. Taken together, our results suggest that such systems may provide a therapeutic approach for treating memory dysfunction.
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http://dx.doi.org/10.1038/s41467-017-02753-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802791PMC
February 2018

Association of Opioid Usage with Spinal Cord Stimulation Outcomes.

Pain Med 2018 04;19(4):699-707

Pain Diagnostics and Interventional Care, Sewickley, Pennsylvania, USA.

Study Design: Observational study using insurance claims.

Objective: To quantify opioid usage leading up to spinal cord stimulation (SCS) and the potential impact on outcomes of SCS.

Setting: SCS is an interventional therapy that often follows opioid usage in the care continuum for chronic pain.

Methods: This study identified SCS patients using the Truven Health MarketScan databases from January 2010 to December 2014. The index event was the first occurrence of a permanent SCS implant. Indicators of opioid usage at implant were daily morphine equivalent dose (MED), number of unique pain drug classes, and diagnosis code for opioid abuse. System explant was used as a measure of ineffective SCS therapy. Multivariate logistic regression was used to analyze the effect of pre-implant medications on explants.

Results: A total of 5,476 patients (56 ± 14 years; 60% female) were included. SCS system removal occurred in 390 patients (7.1%) in the year after implant. Number of drug classes (odds ratio [OR] = 1.11, P = 0.007) and MED level (5-90 vs < 5 mg/d: OR = 1.32, P = 0.043; ≥90 vs < 5 mg/d: OR = 1.57, P = 0.005) were independently predictive of system explant. Over the year before implant, MED increased in 54% (stayed the same in 21%, decreased in 25%) of patients who continued with SCS and increased in 53% (stayed the same in 20%, decreased in 27%) of explant patients (P = 0.772). Over the year after implant, significantly more patients with continued SCS had an MED decrease (47%) or stayed the same (23%) than before (P < 0.001).

Conclusions: Chronic pain patients receive escalating opioid dosage prior to SCS implant, and high-dose opioid usage is associated with an increased risk of explant. Neuromodulation can stabilize or decrease opioid usage. Earlier consideration of SCS before escalated opioid usage has the potential to improve outcomes in complex chronic pain.
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http://dx.doi.org/10.1093/pm/pnx262DOI Listing
April 2018

Dopamine drives left-hemispheric lateralization of neural networks during human speech.

J Comp Neurol 2018 04 21;526(5):920-931. Epub 2017 Dec 21.

Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.

Although the concept of left-hemispheric lateralization of neural processes during speech production has been known since the times of Broca, its physiological underpinnings still remain elusive. We sought to assess the modulatory influences of a major neurotransmitter, dopamine, on hemispheric lateralization during real-life speaking using a multimodal analysis of functional MRI, intracranial EEG recordings, and large-scale neural population simulations based on diffusion-weighted MRI. We demonstrate that speech-induced phasic dopamine release into the dorsal striatum and speech motor cortex exerts direct modulation of neuronal activity in these regions and drives left-hemispheric lateralization of speech production network. Dopamine-induced lateralization of functional activity and networks during speaking is not dependent on lateralization of structural nigro-striatal and nigro-motocortical pathways. Our findings provide the first mechanistic explanation for left-hemispheric lateralization of human speech that is due to left-lateralized dopaminergic modulation of brain activity and functional networks.
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http://dx.doi.org/10.1002/cne.24375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837285PMC
April 2018

Flat-Detector Computed Tomography for Evaluation of Intracerebral Vasculature for Planning of Stereoelectroencephalography Electrode Implantation.

World Neurosurg 2018 Feb 22;110:e585-e592. Epub 2017 Nov 22.

Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Objective: Stereoelectroencephalography (sEEG) requires extensive preoperative planning to optimize placement of electrodes and limit the potential for complications. Flat-detector computed tomography (FD-CT) has previously been used for perioperative vascular imaging to guide the treatment of vascular lesions. This imaging modality provides a detailed depiction of cerebrovascular and bony cranial anatomy, which can be used to guide intracranial electrode implantation. We have developed a novel method to improve preoperative planning for sEEG electrode implantation and limit the potential for postoperative complications by using FD-CT imaging merged with preoperative magnetic resonance imaging (MRI).

Methods: All patients underwent preoperative FD-CT with selective intra-arterial iodinated contrast dye injection through the late arterial and capillary phases for evaluation of cerebrovascular anatomy. These results were merged with thin-cut MRI for trajectory planning of intracranial sEEG electrodes. All patients underwent routine CT and MRI after electrode placement.

Results: 39 patients have undergone sEEG implantation according to this protocol, with a total of 541 electrodes placed. Additionally, 25 (64.1%) patients underwent implantation of 70 oblique insular electrodes. There were no clinically significant complications after the implantations. Thirty-six (92.3%) patients underwent operative intervention, including surgical resection in 27 (69.2%) patients.

Conclusion: FD-CT imaging allows for a detailed depiction of cortical cerebrovascular anatomy through the capillary phase, in addition to bony cranial anatomy. This enables the safe planning of complex trajectories, including high-obliquity insular electrodes and transsulcal trajectories through "empty sulci" while also providing concurrent imaging of bony anatomy to allow for preoperative planning of drill depth and anchor placement.
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http://dx.doi.org/10.1016/j.wneu.2017.11.063DOI Listing
February 2018

Effect of Preoperative Opioid Dosage on Postoperative Period After Thoracic Spinal Cord Stimulator Surgery.

Pain Med 2018 04;19(4):693-698

Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.

Objective: We aim to study the impact of preoperative opioid dosage on postoperative length of stay (LOS) in patients undergoing thoracic spinal cord stimulator (SCS) placement surgery as a primary objective. Secondary objectives of this study include investigating patient-controlled analgesia (PCA) usage and postoperative complications like fever in relation to patients' preoperative opioid dosage and postoperative LOS.

Methods: A total of 47 patients who underwent thoracic SCS for first time were retrospectively studied through chart review. These patients were categorized into two groups, with Group I patients taking a morphine equivalent dose (MED) of less than 100 mg and Group II patients taking an MED of more than 100 mg preoperatively.

Results: Group I had 22 patients, and Group II had 25 patients. The average age in Group I was 53.45 years, and the average age in Group II was 50.16 years. There were seven males (38%) and 15 females (62%) in Group I, and in Group II there were 11 males (44%) and 14 females (56%). The average LOS in both groups was two days. In Group I, there were 16 patients (73%) who had an LOS of one day and six patients (27%) who had an LOS of more than one day, and in Group II there were 11 patients (44%) who had an LOS of less than one day and 14 patients (56%) who had an LOS of more than one day, with a P value of 0.047. On univariate analysis, postoperative fever and PCA usage correlated with longer hospital stay, with a P value of < 0.001.

Conclusion: Patients on high-dose chronic opioid therapy, defined as an MED greater than 100 mg, who undergo thoracic spinal cord stimulator surgery tend to have longer postoperative hospital stays compared with patients on lower-dose opioid therapy.
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http://dx.doi.org/10.1093/pm/pnx250DOI Listing
April 2018

Impact of Trajectory Planning With Susceptibility-Weighted Imaging for Intracranial Electrode Implantation.

Oper Neurosurg (Hagerstown) 2018 07;15(1):60-65

Department of Neurosurgery, Thomas Jefferson University, Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania.

Background: While T1-weighted gadolinium-enhanced (T1-Gd) magnetic resonance imaging (MRI) is the standard imaging sequence for trajectory planning of stereotactic procedures, including deep brain stimulation, stereoelectroencephalography, and laser interstitial thermal therapy, susceptibility-weighted imaging (SWI) has been reported to demonstrate increased sensitivity for the visualization of microvasculature.

Objective: To determine the impact of SWI visualization on trajectory planning for electrode implantation and evaluate the relationship between the rate of vessel-electrode intersections and intracerebral hemorrhage (ICH).

Methods: We conducted a retrospective study of 13 patients who underwent stereoelectroencephalography and laser interstitial thermal therapy placement between 2014 and 2015, using their preoperative T1-Gd and SWI scans, and postoperative MRI scans to determine the rate of vessel-electrode intersections seen on the 2 imaging modalities, the mean diameter and depth of the vessels identified, and the rate of ICH after implantation.

Results: Among 13 patients, 106 electrodes were implanted. Sixty-three unique vessel-electrode intersections were identified on SWI with a mean of 4.85 intersections per patient. There were 13 intersections seen on T1-Gd with a mean of 1 intersection per patient. The intersected vessels visualized on SWI had a diameter of 1.49 ± 0.46 mm and those on T1-Gd were 2.01 ± 0.52 mm. There was no clear ICH observed in this series.

Conclusion: SWI allows for improved visualization of the smaller, deep vessels, whereas T1-Gd adequately detects superficial, larger vessels. Despite the larger number of vessel-electrode intersections seen on SWI, no clear evidence of ICH was identified. Increased detection of deep vasculature does not appear to significantly benefit trajectory planning for stereotactic intracranial procedures and may limit the number of trajectories perceived to be safe.
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http://dx.doi.org/10.1093/ons/opx215DOI Listing
July 2018

Suture Choice in Lumbar Dural Closure Contributes to Variation in Leak Pressures: Experimental Model.

Clin Spine Surg 2017 Jul;30(6):272-275

Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, PA.

Study Design: Open-label laboratory investigational study; non-animal surgical simulation.

Objective: The authors perform a comparison of dural closure strength in a durotomy simulator across 2 different suture materials.

Summary Of Background Data: Incidental durotomy leading to persistent cerebrospinal fluid leak adds considerable morbidity to spinal procedures, often complicating routine elective lumbar spinal procedures. Using an experimental durotomy simulation, the authors compare the strength of closure using Gore-Tex with other suture types and sizes, using various closure techniques.

Methods: A comparison of dural closures was performed through an analysis of the peak pressure at which leakage occurred from a standardized durotomy closure in an established cerebrospinal fluid repair model with a premade L3 laminectomy. Nurolon was compared with Gore-Tex sutures sizes (for Gore-Tex, CV-6/5-0 and CV-5/4-0 was compared with Nurolon 4-0, 5-0, and 6-0).

Results: Thirty-six trials were performed with Nurolon 4-0, 5-0, and 6-0, whereas 21 trials were performed for 4-0 and 5-0 Gore-Tex. The mean peak pressure at which fluid leakage was observed was 21 cm H2O for Nurolon and 34 cm H2O for Gore-Tex. Irrespective of suture choice, all trials were grouped by closure technique: running suture, locked continuous, and interrupted suture. No significant difference was noted between the groups. For each of the 3 trials groups by closure technique, running, locked continuous, and interrupted, Gore-Tex closures had a significantly higher peak pressure to failure. Interrupted Gore-Tex was significantly higher than Interrupted Nurolon (P=0.007), running Gore-Tex was significantly higher than running Nurolon (P=0.034), and locked Gore-Tex was significantly higher than locked Nurolon (P=0.014).

Conclusions: Durotomy closure in the lumbar spine with Gore-Tex suture may be a reasonable option for providing a watertight closure. In this laboratory study, Gore-Tex suture provided watertight dural closures that withstood higher peak pressures.
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http://dx.doi.org/10.1097/BSD.0000000000000169DOI Listing
July 2017