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Mahesh Karandikar, Robert F. Yellon, Geoffrey Murdoch, and Stephanie Greene

Dermoid cysts, encephaloceles, and dermal sinus tracts represent abnormalities that develop during the process of embryogenesis. The elucidation of the precise timing of formation for these malformations has remained elusive at the molecular level of study. Yet, clinical experience has demonstrated that these malformations do not all occur in the same patient, suggesting a shared pathway that goes awry at distinct points for different patients, resulting in 1 of the 3 malformations. Herein the authors describe a case in which all 3 malformations were present in a single patient. This is the first description in the English literature of a sincipital encephalocele occurring with a dermoid cyst and a dermal sinus tract.

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Stephanie Adamczak, Gordon Dale, Juan Pablo de Rivero Vaccari, M. Ross Bullock, W. Dalton Dietrich, and Robert W. Keane

Object

Traumatic brain injury (TBI), the third most common CNS pathology, plagues 5.3 million Americans with permanent TBI-related disabilities. To evaluate injury severity and prognosis, physicians rely on clinical variables. Here, the authors seek objective, biochemical markers reflecting molecular injury mechanisms specific to the CNS as more accurate measurements of injury severity and outcome. One such secondary injury mechanism, the innate immune response, is regulated by the inflammasome, a molecular platform that activates caspase-1 and interleukin-1β.

Methods

The authors investigated whether inflammasome components were present in the CSF of 23 patients with TBI and whether levels of inflammasome components correlate with outcome. The authors performed an immunoblot analysis of CSF samples from patients who suffered TBI and nontrauma controls and assessed the outcomes 5 months postinjury by using the Glasgow Outcome Scale. Data were analyzed using Mann-Whitney U-tests and linear regression analysis.

Results

Patients with severe or moderate cranial trauma exhibited significantly higher CSF levels of the inflammasome proteins ASC, caspase-1, and NALP-1 than nontrauma controls (p < 0.0001, p = 0.0029, and p = 0.0202, respectively). Expression of each protein correlated significantly with the Glasgow Outcome Scale score at 5 months postinjury (p < 0.05). ASC, caspase-1, and NALP-1 were significantly higher in the CSF of patients with unfavorable outcomes, including death and severe disability (p < 0.0001).

Conclusions

NALP-1 inflammasome proteins are potential biomarkers to assess TBI severity, outcome, and the secondary injury mechanisms impeding recovery, serving as adjuncts to clinical predictors.

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Terrance M. Darcey, Erik J. Kobylarz, Michael A. Pearl, Patricia J. Krauss, Stephanie A. Ferri, David W. Roberts, and David F. Bauer

OBJECTIVE

The purpose of this study was to develop safe, site-specific procedures for placing and leaving subdermal needle leads for intraoperative monitoring (IOM) during intraoperative MRI procedures.

METHODS

The authors tested a variety of standard subdermal needle electrodes designed and FDA-approved for IOM in the conventional operating room. Testing was used to determine the conditions necessary to avoid thermal injury and significant image artifacts with minimal disruption of IOM and MRI procedures. Phantom testing was performed with a fiber optic (lead) temperature monitoring system and was followed by testing of leads placed in a healthy volunteer. The volunteer testing used electrode placements typical of standard IOM cases, together with radiofrequency (RF) coil placement and imaging sequences routinely employed for these case types. Lead length was investigated to assess heating effects for electrodes placed within the RF coil.

RESULTS

The authors found that conventional stainless steel (SS) and platinum/iridium (Pt/Ir) subdermal needles can be used safely without significant heating when placed outside the RF coil, and this accounts for the majority or entirety of electrode placements. When placed within the RF coil, Pt/Ir leads produced minimal image artifacts, while SS leads produced potentially significant artifacts. In phantom testing, significant heating was demonstrated in both SS and Pt/Ir leads placed within the RF coil, but only during high-resolution T2-weighted scanning. This problem was largely, but not completely, eliminated when leads were shortened to 25 cm. Human testing was unremarkable except for nonpainful heating detected in a few electrodes during thin-slice (1.5 mm) FLAIR scanning. Transient irritation (skin reddening along the needle tract) was noted at 2 of the electrodes with detectable heating.

CONCLUSIONS

The authors were satisfied with the safety of their site-specific procedures and have begun with off-label use (following institutional review board approval and obtaining patient informed consent) of tested monitoring leads in cases that combine IOM and MRI. The authors recommend that all facilities perform their own site-specific testing of monitoring leads before proceeding with their routine use.

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Dallas L. Sheinberg, David J. McCarthy, Omar Elwardany, Jean-Paul Bryant, Evan Luther, Stephanie H. Chen, John W. Thompson, and Robert M. Starke

Endothelial cell (EC) dysfunction is known to contribute to cerebral aneurysm (CA) pathogenesis. Evidence shows that damage or injury to the EC layer is the first event in CA formation. The mechanisms behind EC dysfunction in CA disease are interrelated and include hemodynamic stress, hazardous nitric oxide synthase (NOS) activity, oxidative stress, estrogen imbalance, and endothelial cell-to-cell junction compromise. Abnormal variations in hemodynamic stress incite pathological EC transformation and inflammatory zone formation, ultimately leading to destruction of the vascular wall and aneurysm dilation. Hemodynamic stress activates key molecular pathways that result in the upregulation of chemotactic cytokines and adhesion molecules, leading to inflammatory cell recruitment and infiltration. Concurrently, oxidative stress damages EC-to-EC junction proteins, resulting in interendothelial gap formation. This further promotes leukocyte traffic into the vessel wall and the release of matrix metalloproteinases, which propagates vascular remodeling and breakdown. Abnormal hemodynamic stress and inflammation also trigger adverse changes in NOS activity, altering proper EC mediation of vascular tone and the local inflammatory environment. Additionally, the vasoprotective hormone estrogen modulates gene expression that often suppresses these harmful processes. Crosstalk between these sophisticated pathways contributes to CA initiation, progression, and rupture. This review aims to outline the complex mechanisms of EC dysfunction in CA pathogenesis.

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Robert Kellogg, Philip Lee, Christopher P. Deibert, Zachary Tempel, Nathan T. Zwagerman, Christopher M. Bonfield, Stephen Johnson, and Stephanie Greene

OBJECTIVE

The authors reviewed 20 years’ experience with the surgical management of open myelomeningocele in a well-defined retrospective cohort from a single large academic medical center. Their goal was to define the characteristics of a modern cohort of children with myelomeningocele to allow for evidence-based decision-making for the treatment of these patients.

METHODS

After IRB approval was obtained, the authors queried an operative database maintained by the Department of Neurological Surgery at Children’s Hospital of Pittsburgh for patients who underwent closure of a myelomeningocele between 1995 and 2015. They identified 153 infants, and a retrospective chart review was performed.

RESULTS

Eighty-eight percent of the patients required placement of a ventriculoperitoneal shunt, and 15% of these patients acquired shunt-related infections. Eighteen percent of patients underwent Chiari malformation type II (CM-II) decompression. Sixteen percent of patients underwent a tethered cord release. Three percent of patients died within the 1st year of life. Predictors of an early demise included poor Apgar scores, large head circumference, and need for early CM-II decompression. Functional motor outcome was slightly better than predicted by anatomical level of defect.

CONCLUSIONS

Myelomeningoceles represent a severe birth defect with life-threatening complications. The authors provide long-term follow-up data and insight into factors that contribute to early death.

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Robert T. Buckley, Weihong Yuan, Francesco T. Mangano, Jannel M. Phillips, Stephanie Powell, Robert C. McKinstry, Akila Rajagopal, Blaise V. Jones, Scott Holland, and David D. Limbrick Jr.

The authors report the case of a 25-month-old boy who underwent endoscopic third ventriculostomy (ETV) for hydrocephalus resulting from aqueductal stenosis. The patient's recovery was monitored longitudinally and prospectively using MR diffusion tensor imaging (DTI) and formal neuropsychological testing. Despite minimal change in ventricle size, improvement in the DTI characteristics and neurodevelopmental trajectory was observed following ETV. These data support the use of DTI as a biomarker to assess therapeutic response in children undergoing surgical treatment for hydrocephalus. In the patient featured in this report, DTI appeared to provide more information regarding postoperative neurodevelopmental outcome than ventricle size alone.

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John W. Gilbert, Robert E. Windsor, Gregory E. Mick, Stephanie Herder, and Gay B. Richardson

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Robert J. Ogg, Fred H. Laningham, Dave Clarke, Stephanie Einhaus, Ping Zou, Michael E. Tobias, and Frederick A. Boop

Object

In this study, the authors examined whether passive range of motion (ROM) under conscious sedation could be used to localize sensorimotor cortex using functional MR (fMR) imaging in children as part of their presurgical evaluation.

Methods

After obtaining institutional review board approval (for retrospective analysis of imaging data acquired for clinical purposes) and informed consent, 16 children underwent fMR imaging. All 16 had lesions; masses were found in 9 patients and cortical dysplasia was found in 4; the lesions in 3 patients were not diagnosed. Passive ROM was performed during blood oxygen level–dependent MR imaging sequences. Three of the patients also performed active motor tasks during the fMR imaging study. All patients were evaluated using passive ROM of the hand and/or foot; 3 patients were evaluated for passive touch of the face. In 9 cases, intraoperative electrocorticography (ECoG) was used. Five of the patients underwent intraoperative ECoG to evaluate for seizure activity. Four patients had intraoperative ECoG for motor mapping. Five of the patients had subdural grids placed for extraoperative monitoring.

Results

In 3 cases, the active and passive ROMs colocalized. In 4 patients ECoG was used to identify motor cortex, and in all 4 motor ECoG yielded results consistent with the passive ROM localization. Thirteen of 16 children have undergone resection based on passive ROM fMR imaging findings with no unanticipated deficits.

Conclusions

These preliminary data suggest that passive ROM fMR imaging can accurately detect functional hand, leg, and face regions of the sensorimotor cortex in the sedated child. This extends current extraoperative mapping capabilities to patients unable or unwilling to cooperate for active motor tasks.

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John W. Thompson, Omar Elwardany, David J. McCarthy, Dallas L. Sheinberg, Carlos M. Alvarez, Ahmed Nada, Brian M. Snelling, Stephanie H. Chen, Samir Sur, and Robert M. Starke

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.

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Anshit Goyal, Stephanie Payne, Lindsey R. Sangaralingham, Molly Moore Jeffery, James M. Naessens, Halena M. Gazelka, Elizabeth B. Habermann, William Krauss, Robert J. Spinner, and Mohamad Bydon

OBJECTIVE

Sustained postoperative opioid use after elective surgery is a matter of growing concern. Herein, the authors investigated incidence and predictors of long-term opioid use among patients undergoing elective lumbar spine surgery, especially as a function of opioid prescribing practices at postoperative discharge (dose in morphine milligram equivalents [MMEs] and type of opioid).

METHODS

The OptumLabs Data Warehouse (OLDW) was queried for postdischarge opioid prescriptions for patients undergoing elective lumbar decompression and discectomy (LDD) or posterior lumbar fusion (PLF) for degenerative spine disease. Only patients who received an opioid prescription at postoperative discharge and those who had a minimum of 180 days of insurance coverage prior to surgery and 180 days after surgery were included. Opioid-naive patients were defined as those who had no opioid fills in 180 days prior to surgery. The following patterns of long-term postoperative use were investigated: additional fills (at least one opioid fill 90–180 days after surgery), persistent fills (any span of opioid use starting in the 180 days after surgery and lasting at least 90 days), and Consortium to Study Opioid Risks and Trends (CONSORT) criteria for persistent use (episodes of opioid prescribing lasting longer than 90 days and 120 or more total days’ supply or 10 or more prescriptions in 180 days after the index fill). Multivariable logistic regression was performed to identify predictors of long-term use.

RESULTS

A total of 25,587 patients were included, of whom 52.7% underwent PLF (n = 13,486) and 32.5% (n = 8312) were opioid-naive prior to surgery. The rates of additional fills, persistent fills, and CONSORT use were 47%, 30%, and 23%, respectively, after PLF and 35.4%, 19%, and 14.2%, respectively, after LDD. The rates among opioid-naive patients were 18.9%, 5.6%, and 2.5% respectively, after PLF and 13.3%, 2.0%, and 0.8%, respectively, after LDD. Using multivariable logistic regression, the following were identified to be significantly associated with higher risk of long-term opioid use following PLF: discharge opioid prescription ≥ 500 MMEs, prescription of a long-acting opioid, female sex, multilevel surgery, and comorbidities such as depression and drug abuse (all p < 0.05). Elderly (age ≥ 65 years) and opioid-naive patients were found to be at lower risk (all p < 0.05). Similar results were obtained on analysis for LDD with the following significant additional risk factors identified: discharge opioid prescription ≥ 400 MMEs, prescription of tramadol alone at discharge, and inpatient surgery (all p < 0.05).

CONCLUSIONS

In an analysis of pharmacy claims from a national insurance database, the authors identified incidence and predictors of long-term opioid use after elective lumbar spine surgery.