Publications by authors named "Elizabeth Tyler-Kabara"

82 Publications

Long-term outcomes in the treatment of pediatric skull base chordomas in the endoscopic endonasal era.

J Neurosurg Pediatr 2020 Nov 20:1-10. Epub 2020 Nov 20.

Departments of1Neurological Surgery and.

Objective: Pediatric skull base chordoma is a rare entity that is traditionally considered to display aggressive behavior with an increased risk of recurrence. There is an absence of literature examining outcomes in the pediatric population in general and using the endoscopic endonasal approach (EEA).

Methods: The authors retrospectively reviewed all patients with skull base chordomas presenting by the age of 18 years to the Children's Hospital of Pittsburgh or the University of Pittsburgh Medical Center from 2004 to 2019. Clinical outcomes, the number and location of recurrences, and progression-free survival time were determined.

Results: Twenty patients met the study criteria. The most common presenting complaints were diplopia (n = 7), headache (n = 6), and swallowing difficulty (n = 4). Three cases were incidentally discovered. Twelve patients underwent single-stage EEA alone, 2 patients had two-stage EEA, and 6 patients had combined EEA with open far-lateral or extreme-lateral approaches. Fourteen patients underwent gross-total resection (GTR), and 6 patients had near-total resection. Larger tumors were more likely to require staging or a combined approach (86% vs 7%) and were less likely to receive GTR (33% vs 86%) but had comparable recurrence and mortality rates. Five patients developed CSF leaks requiring reoperation, 2 patients developed a permanent abducens nerve palsy, 1 patient suffered an internal carotid artery injury, 1 patient developed an epidural hematoma, and 1 patient developed a subdural empyema. Four (20%) patients had recurrence during follow-up (mean radiographic follow-up 59 months and mean time to local recurrence 19 months). Two patients with recurrence underwent further resection, and 1 patient elected to stop treatment. Both patients who underwent repeat resection experienced a second recurrence, one of whom elected to stop treatment. Both patients who died had an elevated Ki-67 (p = 0.039), one of whom developed de-differentiated histology. A third patient died of progressive spinal metastases without local recurrence and is one of 2 patients who developed postoperative spinal metastases. Both patients whose tumors became de-differentiated progressed from tumors with an initial Ki-67 of 15 or greater (p = 0.035) and received prior radiotherapy to the bulk tumor (p = 0.03).

Conclusions: The majority of pediatric skull base chordomas, when managed at a specialized center with a goal of GTR, may have a better outcome than traditionally believed. Elevated Ki-67 rates may predict poor outcome and progression to de-differentiation.
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http://dx.doi.org/10.3171/2020.6.PEDS19733DOI Listing
November 2020

Robust deep learning classification of adamantinomatous craniopharyngioma from limited preoperative radiographic images.

Sci Rep 2020 10 9;10(1):16885. Epub 2020 Oct 9.

Division of Pediatric Neurosurgery, Children's Hospital Colorado, Aurora, 80045, USA.

Deep learning (DL) is a widely applied mathematical modeling technique. Classically, DL models utilize large volumes of training data, which are not available in many healthcare contexts. For patients with brain tumors, non-invasive diagnosis would represent a substantial clinical advance, potentially sparing patients from the risks associated with surgical intervention on the brain. Such an approach will depend upon highly accurate models built using the limited datasets that are available. Herein, we present a novel genetic algorithm (GA) that identifies optimal architecture parameters using feature embeddings from state-of-the-art image classification networks to identify the pediatric brain tumor, adamantinomatous craniopharyngioma (ACP). We optimized classification models for preoperative Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and combined CT and MRI datasets with demonstrated test accuracies of 85.3%, 83.3%, and 87.8%, respectively. Notably, our GA improved baseline model performance by up to 38%. This work advances DL and its applications within healthcare by identifying optimized networks in small-scale data contexts. The proposed system is easily implementable and scalable for non-invasive computer-aided diagnosis, even for uncommon diseases.
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http://dx.doi.org/10.1038/s41598-020-73278-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547020PMC
October 2020

Endoscopic Endonasal Approach for Craniopharyngiomas with Intraventricular Extension: Case Series, Long-Term Outcomes, and Review.

World Neurosurg 2020 Dec 2;144:e447-e459. Epub 2020 Sep 2.

Department of Neurological Surgery, University of Pittsburgh Medical Center, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania, USA.

Background: Traditionally, craniopharyngiomas with intraventricular extension were approached transcranially; however, endoscopic approaches are now increasingly used. We sought to study the endoscopic endonasal approach (EEA) in the setting of complex craniopharyngiomas with intraventricular extension and to compare it with existing literature.

Methods: Patients undergoing EEA for resection of craniopharyngioma with ventricular involvement from 2002 to 2015 were retrospectively reviewed. Outcomes were compared with previously published EEA and transcranial approach (TCA) studies for all craniopharyngioma locations.

Results: Sixty-two patients were included. Average tumor and intraventricular volume were 13.93 cm and 2.61 cm, respectively. Patients presented with visual impairment, endocrinopathy, and, headache. Gross total resection (GTR) was achieved in 47% of all cases and increased to 77% after 2012 Approximately 98% experienced improvement or stability of vision. Postoperative cerebrospinal fluid (CSF) leak and meningitis rates were 19% and 8.1%, respectively. However, nasoseptal flap (NSF) use reduced CSF leak rate to 10%. Six (9.6%) patients required shunting before resection and 25% were shunted postoperatively. Seven of 10 patients (70%) treated before NSF use required shunting, whereas only 7 of 46 (15%) required shunting with NSF reconstruction. Review demonstrated similar outcomes between the present cohort and EEA or TCA for all craniopharyngioma locations. TCA had a greater GTR, however, with large study variation. EEA showed improved visual outcomes but also increased CSF leaks.

Conclusions: EEA for craniopharyngiomas with intraventricular extension shows similar outcomes to TCA and EEA for all craniopharyngiomas, expanding this anatomic limit. Given ventricular involvement, CSF leak rates are expectedly high. GTR increased and CSF leak rates dramatically decreased with time, suggestive of the steep learning curve to complex resection.
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http://dx.doi.org/10.1016/j.wneu.2020.08.184DOI Listing
December 2020

Stabilization of a brain-computer interface via the alignment of low-dimensional spaces of neural activity.

Nat Biomed Eng 2020 07 20;4(7):672-685. Epub 2020 Apr 20.

Department of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.

The instability of neural recordings can render clinical brain-computer interfaces (BCIs) uncontrollable. Here, we show that the alignment of low-dimensional neural manifolds (low-dimensional spaces that describe specific correlation patterns between neurons) can be used to stabilize neural activity, thereby maintaining BCI performance in the presence of recording instabilities. We evaluated the stabilizer with non-human primates during online cursor control via intracortical BCIs in the presence of severe and abrupt recording instabilities. The stabilized BCIs recovered proficient control under different instability conditions and across multiple days. The stabilizer does not require knowledge of user intent and can outperform supervised recalibration. It stabilized BCIs even when neural activity contained little information about the direction of cursor movement. The stabilizer may be applicable to other neural interfaces and may improve the clinical viability of BCIs.
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http://dx.doi.org/10.1038/s41551-020-0542-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822646PMC
July 2020

Classification of Individual Finger Movements Using Intracortical Recordings in Human Motor Cortex.

Neurosurgery 2020 09;87(4):630-638

Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Intracortical microelectrode arrays have enabled people with tetraplegia to use a brain-computer interface for reaching and grasping. In order to restore dexterous movements, it will be necessary to control individual fingers.

Objective: To predict which finger a participant with hand paralysis was attempting to move using intracortical data recorded from the motor cortex.

Methods: A 31-yr-old man with a C5/6 ASIA B spinal cord injury was implanted with 2 88-channel microelectrode arrays in left motor cortex. Across 3 d, the participant observed a virtual hand flex in each finger while neural firing rates were recorded. A 6-class linear discriminant analysis (LDA) classifier, with 10 × 10-fold cross-validation, was used to predict which finger movement was being performed (flexion/extension of all 5 digits and adduction/abduction of the thumb).

Results: The mean overall classification accuracy was 67% (range: 65%-76%, chance: 17%), which occurred at an average of 560 ms (range: 420-780 ms) after movement onset. Individually, thumb flexion and thumb adduction were classified with the highest accuracies at 92% and 93%, respectively. The index, middle, ring, and little achieved an accuracy of 65%, 59%, 43%, and 56%, respectively, and, when incorrectly classified, were typically marked as an adjacent finger. The classification accuracies were reflected in a low-dimensional projection of the neural data into LDA space, where the thumb-related movements were most separable from the finger movements.

Conclusion: Classification of intention to move individual fingers was accurately predicted by intracortical recordings from a human participant with the thumb being particularly independent.
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http://dx.doi.org/10.1093/neuros/nyaa026DOI Listing
September 2020

Extensive tumor calcification in response to pre-operative reductive chemotherapy in pediatric esthesioneuroblastoma: a case report.

Childs Nerv Syst 2020 09 26;36(9):2099-2102. Epub 2020 Feb 26.

Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA.

Esthesioneuroblastomas are uncommon tumors in pediatric patients and are typically treated with multimodal therapy. Changes in gross tumor quality and character in response to adjuvant treatment have not been clearly reported. We report the case of a 15-year-old female with a diagnosis of Kadish stage C esthesioneuroblastoma who was treated with neoadjuvant chemotherapy and surgical resection. The patient's tumor demonstrated cytoreduction after chemotherapy but also was found to have calcified. A combined trans-frontal sinus craniotomy with endoscopic endonasal resection was performed and resulted in negative margins and good clinical outcome.
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http://dx.doi.org/10.1007/s00381-020-04545-2DOI Listing
September 2020

Radiological and clinical predictors of scoliosis in patients with Chiari malformation type I and spinal cord syrinx from the Park-Reeves Syringomyelia Research Consortium.

J Neurosurg Pediatr 2019 Aug 16:1-8. Epub 2019 Aug 16.

1Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.

Objective: Scoliosis is frequently a presenting sign of Chiari malformation type I (CM-I) with syrinx. The authors' goal was to define scoliosis in this population and describe how radiological characteristics of CM-I and syrinx relate to the presence and severity of scoliosis.

Methods: A large multicenter retrospective and prospective registry of pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for clinical and radiological characteristics of CM-I, syrinx, and scoliosis (coronal curve ≥ 10°).

Results: Based on available imaging of patients with CM-I and syrinx, 260 of 825 patients (31%) had a clear diagnosis of scoliosis based on radiographs or coronal MRI. Forty-nine patients (5.9%) did not have scoliosis, and in 516 (63%) patients, a clear determination of the presence or absence of scoliosis could not be made. Comparison of patients with and those without a definite scoliosis diagnosis indicated that scoliosis was associated with wider syrinxes (8.7 vs 6.3 mm, OR 1.25, p < 0.001), longer syrinxes (10.3 vs 6.2 levels, OR 1.18, p < 0.001), syrinxes with their rostral extent located in the cervical spine (94% vs 80%, OR 3.91, p = 0.001), and holocord syrinxes (50% vs 16%, OR 5.61, p < 0.001). Multivariable regression analysis revealed syrinx length and the presence of holocord syrinx to be independent predictors of scoliosis in this patient cohort. Scoliosis was not associated with sex, age at CM-I diagnosis, tonsil position, pB-C2 distance (measured perpendicular distance from the ventral dura to a line drawn from the basion to the posterior-inferior aspect of C2), clivoaxial angle, or frontal-occipital horn ratio. Average curve magnitude was 29.9°, and 37.7% of patients had a left thoracic curve. Older age at CM-I or syrinx diagnosis (p < 0.0001) was associated with greater curve magnitude whereas there was no association between syrinx dimensions and curve magnitude.

Conclusions: Syrinx characteristics, but not tonsil position, were related to the presence of scoliosis in patients with CM-I, and there was an independent association of syrinx length and holocord syrinx with scoliosis. Further study is needed to evaluate the nature of the relationship between syrinx and scoliosis in patients with CM-I.
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http://dx.doi.org/10.3171/2019.5.PEDS18527DOI Listing
August 2019

New neural activity patterns emerge with long-term learning.

Proc Natl Acad Sci U S A 2019 07 10;116(30):15210-15215. Epub 2019 Jun 10.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213;

Learning has been associated with changes in the brain at every level of organization. However, it remains difficult to establish a causal link between specific changes in the brain and new behavioral abilities. We establish that new neural activity patterns emerge with learning. We demonstrate that these new neural activity patterns cause the new behavior. Thus, the formation of new patterns of neural population activity can underlie the learning of new skills.
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http://dx.doi.org/10.1073/pnas.1820296116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660765PMC
July 2019

The Incidence of Chiari Malformations in Patients with Isolated Sagittal Synostosis.

Plast Reconstr Surg Glob Open 2019 Feb 12;7(2):e2090. Epub 2019 Feb 12.

Department of Ophthalmology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.

Background: We report the incidence of Chiari malformation I (CMI) in a cohort of 377 patients with isolated sagittal synostosis (ISS), which is to the best of our knowledge the largest such series reported to date.

Methods: A retrospective review of patients seen at a single institution from 2007 to 2017 was completed. ISS, Chiari malformations (CMI and CMII) and hydrocephalus were diagnosed by a senior neuroradiologist (G.Z.). Patients who met the inclusion criteria were divided into early (group A) and late (group B) presenting groups, as well as operated (group I) and unoperated (group II) groups. The patients were further subdivided into group AI (early operated), group AII (early unoperated), group BI (late operated), and group BII (late unoperated). Once identified, patient notes were examined for the following data sets: date of birth, age of presentation, age at last follow-up, other systemic conditions as well as molecular testing results. Surgical interventions, ophthalmological, and other relevant data were recorded. Statistical analysis was run in the form of a chi-square test to identify a significant difference between each subgroup. A literature review of the incidence of Chiari malformations in patients with ISS was conducted.

Results: Three hundred seventy-seven patients constitute the study's total cohort (272 were males and 105 females). This cohort was divided into patients who underwent surgical repair of ISS (group 1: n = 200), and patients who did not (group 2: n = 177). The entire cohort was also divided into early (group A: n = 161) and late (group B: n = 216) presenting craniosynostosis. In the total cohort, 22/377 (5.8%) patients with CMI were identified. CMI was found in 14/200 (7.0%) patients in group I, and 8/177 (4.5%) patients in group II. CMI was found in 2/161 (1%) patients in group A, and 20/216 (9.2%) patients in group B. The incidence of CMI in group AI (early operated) was 2/151 (1.3%), in group AII (early unoperated) was 0/10, in group BI (late operated) was 11/49 (21%), and in group BII (late unoperated) was 9/167 (5.4%). Chi-square analysis revealed a significant difference between the incidence of CMI in the early-presenting (group A) and late-presenting (group B) groups ( = 0.001) and between the late-presenting operated (BI) and late-presenting unoperated (BII) groups ( = 0.001). The incidence of hydrocephalus was 1.6% (6/377) in the total cohort. However, all patients diagnosed with hydrocephalus came from group II (no surgical ISS correction). The incidence of hydrocephalus in group II was 3.3% (6/177). The incidence of hydrocephalus in group BII (late unoperated ISS) was 3.0% (5/167). The incidence of hydrocephalus in group AII (early unoperated ISS) was 9.0% (1/11).

Conclusions: We noted the highest incidence of CMI-21%-in group BI (late-presenting operated). We noted hydrocephalus in group II (nonoperated), with the highest incidence of hydrocephalus found in the group BII (late-presenting unoperated) subgroup. We therefore recommend patients with ISS receive funduscopic examination to screen for raised intracranial pressure (ICP) associated with CMI and hydrocephalus, especially patients with late-presenting ISS.
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http://dx.doi.org/10.1097/GOX.0000000000002090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416108PMC
February 2019

Long-term impact of pediatric endoscopic endonasal skull base surgery on midface growth.

J Neurosurg Pediatr 2019 01;23(4):523-530

Departments of1Plastic Surgery.

Objective: Cranial base development plays a large role in anterior and vertical maxillary growth through 7 years of age, and the effect of early endonasal cranial base surgery on midface growth is unknown. The authors present their experience with pediatric endoscopic endonasal surgery (EES) and long-term midface growth.

Methods: This is a retrospective review of cases where EES was performed from 2000 to 2016. Patients who underwent their first EES of the skull base before age 7 (prior to cranial suture fusion) and had a complete set of pre- and postoperative imaging studies (CT or MRI) with at least 1 year of follow-up were included. A radiologist performed measurements (sella-nasion [S-N] distance and angles between the sella, nasion, and the most concave points of the anterior maxilla [A point] or anterior mandibular synthesis [B point], the SNA, SNB, and ANB angles), which were compared to age- and sex-matched Bolton standards. A Z-score test was used; significance was set at p < 0.05.

Results: The early surgery group had 11 patients, with an average follow-up of 5 years; the late surgery group had 33 patients. Most tumors were benign; 1 patient with a panclival arteriovenous malformation was a significant outlier for all measurements. Comparing the measurements obtained in the early surgery group to Bolton standard norms, the authors found no significant difference in postoperative SNA (p = 0.10), SNB (p = 0.14), or ANB (0.67) angles. The S-N distance was reduced both pre- and postoperatively (SD 1.5, p = 0.01 and p = 0.009). Sex had no significant effect. Compared to patients who had surgery after the age of 7 years, the early surgery group demonstrated no significant difference in pre- to postoperative changes with regard to S-N distance (p = 0.87), SNA angle (p = 0.89), or ANB angle (p = 0.14). Lesion type (craniopharyngioma, angiofibroma, and other types) had no significant effect in either age group.

Conclusions: Though our cohort of patients with skull base lesions demonstrated some abnormal measurements in the maxillary-mandibular relationship before their operation, their postoperative cephalometrics fell within the normal range and showed no significant difference from those of patients who underwent operations at an older age. Therefore, there appears to be no evidence of impact of endoscopic endonasal skull base surgery on craniofacial development within the growth period studied.
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http://dx.doi.org/10.3171/2018.8.PEDS18183DOI Listing
January 2019

Bilateral endoscopic optic nerve decompression in an infant with osteopetrosis.

J AAPOS 2019 02 29;23(1):40-42. Epub 2018 Aug 29.

Department of Ophthalmology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.

Osteopetrosis is a rare disorder of bone remodeling characterized by defective resorption leading to excessive skeletal mass including optic canal. Compression of the optic nerve from the narrowed optic canal is the most common cause of vision loss in children with osteopetrosis. We report the case of a 6-month old girl with osteopetrosis who underwent bilateral optic canal decompression via endoscopic transcaruncular approach for progressive deterioration of visual function secondary to compressive optic neuropathy from narrowed optic canals. The patient showed improvement in visual function postoperatively.
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http://dx.doi.org/10.1016/j.jaapos.2018.05.012DOI Listing
February 2019

Constraints on neural redundancy.

Elife 2018 08 15;7. Epub 2018 Aug 15.

Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, United States.

Millions of neurons drive the activity of hundreds of muscles, meaning many different neural population activity patterns could generate the same movement. Studies have suggested that these redundant (i.e. behaviorally equivalent) activity patterns may be beneficial for neural computation. However, it is unknown what constraints may limit the selection of different redundant activity patterns. We leveraged a brain-computer interface, allowing us to define precisely which neural activity patterns were redundant. Rhesus monkeys made cursor movements by modulating neural activity in primary motor cortex. We attempted to predict the observed distribution of redundant neural activity. Principles inspired by work on muscular redundancy did not accurately predict these distributions. Surprisingly, the distributions of redundant neural activity and task-relevant activity were coupled, which enabled accurate predictions of the distributions of redundant activity. This suggests limits on the extent to which redundancy may be exploited by the brain for computation.
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http://dx.doi.org/10.7554/eLife.36774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130976PMC
August 2018

Publisher Correction: Learning by neural reassociation.

Nat Neurosci 2018 Aug;21(8):1138

Department of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.

In the version of this article initially published, equation (10) contained cos Θ instead of sin Θ as the bottom element of the right-hand vector. The error has been corrected in the HTML and PDF versions of the article.
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http://dx.doi.org/10.1038/s41593-018-0185-2DOI Listing
August 2018

Endoscopic endonasal surgery for epidermoid and dermoid cysts: a 10-year experience.

J Neurosurg 2018 Mar 1:1-11. Epub 2018 Mar 1.

1Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

OBJECTIVEEpidermoid and dermoid cysts may be found along the cranial base and are commonly resected via open transcranial approaches. The use of endoscopic endonasal approaches for resection of these tumors has been rarely reported.METHODSThe authors retrospectively reviewed the medical records of 21 patients who underwent endoscopic endonasal surgery for epidermoid and dermoid cyst resection at the University of Pittsburgh Medical Center between January 2005 and June 2014. Surgical outcomes and variables that might affect the extent of resection and complications were analyzed.RESULTSTotal resection (total removal of cyst contents and capsule) was achieved in 8 patients (38.1%), near-total resection (total removal of cyst contents, incomplete removal of cyst capsule) in 9 patients (42.9%), and subtotal resection (incomplete removal of cyst contents and capsule) in 4 patients (19%). Larger cyst volume (≥ 3 cm3) and intradural location (15 cysts) were significantly associated with nontotal resection (p = 0.008 and 0.0005, respectively). In the whole series, surgical complications were seen in 6 patients (28.6%). No complications were observed in patients with extradural cysts. Among the 15 patients with intradural cysts, the most common surgical complication was postoperative CSF leak (5 patients, 33.3%), followed by postoperative intracranial infection (4 patients, 26.7%). Larger cysts and postoperative CSF leak were associated with intracranial infection (p = 0.012 and 0.028, respectively). Subtotal resection was marginally associated with intracranial infection when compared with total resection (p = 0.091). All patients with neurological symptoms improved postoperatively with the exception of 1 patient with unchanged abducens nerve palsy.CONCLUSIONSEndoscopic endonasal approaches may be effectively used for resection of epidermoid and dermoid cysts in carefully selected cases. These approaches are recommended for cases in which a total or near-total resection is possible in addition to a multilayer cranial base reconstruction with vascularized tissue to minimize the risk of intracranial infection.
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http://dx.doi.org/10.3171/2017.7.JNS162783DOI Listing
March 2018

Learning by neural reassociation.

Nat Neurosci 2018 04 12;21(4):607-616. Epub 2018 Mar 12.

Department of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.

Behavior is driven by coordinated activity across a population of neurons. Learning requires the brain to change the neural population activity produced to achieve a given behavioral goal. How does population activity reorganize during learning? We studied intracortical population activity in the primary motor cortex of rhesus macaques during short-term learning in a brain-computer interface (BCI) task. In a BCI, the mapping between neural activity and behavior is exactly known, enabling us to rigorously define hypotheses about neural reorganization during learning. We found that changes in population activity followed a suboptimal neural strategy of reassociation: animals relied on a fixed repertoire of activity patterns and associated those patterns with different movements after learning. These results indicate that the activity patterns that a neural population can generate are even more constrained than previously thought and might explain why it is often difficult to quickly learn to a high level of proficiency.
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http://dx.doi.org/10.1038/s41593-018-0095-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5876156PMC
April 2018

Cervical Spine Injury From Unrecognized Craniocervical Instability in Severe Pierre Robin Sequence Associated With Skeletal Dysplasia.

Cleft Palate Craniofac J 2018 05 28;55(5):773-777. Epub 2018 Feb 28.

1 Division of Pediatric Plastic Surgery, University of Pittsburgh School of Medicine, Pennsylvania, PA, USA.

Pierre Robin Sequence (PRS) can be associated with skeletal dysplasias, presenting with craniocervical instability and devastating spinal injury if unrecognized. The authors present the case of an infant with PRS and a type II collagenopathy who underwent multiple airway-securing procedures requiring spinal manipulation before craniocervical instability was identified. This resulted in severe cervical cord compression due to odontoid fracture and occipitoatlantoaxial instability. This case highlights the importance of early cervical spine imaging and cautious manipulation in infants with PRS and suspected skeletal dysplasia.
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http://dx.doi.org/10.1177/1055665618758102DOI Listing
May 2018

Motor cortical activity changes during neuroprosthetic-controlled object interaction.

Sci Rep 2017 12 5;7(1):16947. Epub 2017 Dec 5.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Brain-computer interface (BCI) controlled prosthetic arms are being developed to restore function to people with upper-limb paralysis. This work provides an opportunity to analyze human cortical activity during complex tasks. Previously we observed that BCI control became more difficult during interactions with objects, although we did not quantify the neural origins of this phenomena. Here, we investigated how motor cortical activity changed in the presence of an object independently of the kinematics that were being generated using intracortical recordings from two people with tetraplegia. After identifying a population-wide increase in neural firing rates that corresponded with the hand being near an object, we developed an online scaling feature in the BCI system that operated without knowledge of the task. Online scaling increased the ability of two subjects to control the robotic arm when reaching to grasp and transport objects. This work suggests that neural representations of the environment, in this case the presence of an object, are strongly and consistently represented in motor cortex but can be accounted for to improve BCI performance.
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http://dx.doi.org/10.1038/s41598-017-17222-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717217PMC
December 2017

In-vivo effects of intraocular and intracranial pressures on the lamina cribrosa microstructure.

PLoS One 2017 21;12(11):e0188302. Epub 2017 Nov 21.

New York University Langone Eye Center, New York University School of Medicine, New York, New York, United States of America.

There is increasing clinical evidence that the eye is not only affected by intraocular pressure (IOP), but also by intracranial pressure (ICP). Both pressures meet at the optic nerve head of the eye, specifically the lamina cribrosa (LC). The LC is a collagenous meshwork through which all retinal ganglion cell axons pass on their way to the brain. Distortion of the LC causes a biological cascade leading to neuropathy and impaired vision in situations such as glaucoma and idiopathic intracranial hypertension. While the effect of IOP on the LC has been studied extensively, the coupled effects of IOP and ICP on the LC remain poorly understood. We investigated in-vivo the effects of IOP and ICP, controlled via cannulation of the eye and lateral ventricle in the brain, on the LC microstructure of anesthetized rhesus monkeys eyes using the Bioptigen spectral-domain optical coherence tomography (OCT) device (Research Triangle, NC). The animals were imaged with their head upright and the rest of their body lying prone on a surgical table. The LC was imaged at a variety of IOP/ICP combinations, and microstructural parameters, such as the thickness of the LC collagenous beams and diameter of the pores were analyzed. LC microstructure was confirmed by histology. We determined that LC microstructure deformed in response to both IOP and ICP changes, with significant interaction between the two. These findings emphasize the importance of considering both IOP and ICP when assessing optic nerve health.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188302PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697865PMC
December 2017

Remapping cortical modulation for electrocorticographic brain-computer interfaces: a somatotopy-based approach in individuals with upper-limb paralysis.

J Neural Eng 2018 04;15(2):026021

Systems Neuroscience Center, University of Pittsburgh, PA, United States of America. Center for the Neural Basis of Cognition, Pittsburgh, PA, United States of America.

Objective: Brain-computer interface (BCI) technology aims to provide individuals with paralysis a means to restore function. Electrocorticography (ECoG) uses disc electrodes placed on either the surface of the dura or the cortex to record field potential activity. ECoG has been proposed as a viable neural recording modality for BCI systems, potentially providing stable, long-term recordings of cortical activity with high spatial and temporal resolution. Previously we have demonstrated that a subject with spinal cord injury (SCI) could control an ECoG-based BCI system with up to three degrees of freedom (Wang et al 2013 PLoS One). Here, we expand upon these findings by including brain-control results from two additional subjects with upper-limb paralysis due to amyotrophic lateral sclerosis and brachial plexus injury, and investigate the potential of motor and somatosensory cortical areas to enable BCI control.

Approach: Individuals were implanted with high-density ECoG electrode grids over sensorimotor cortical areas for less than 30 d. Subjects were trained to control a BCI by employing a somatotopic control strategy where high-gamma activity from attempted arm and hand movements drove the velocity of a cursor.

Main Results: Participants were capable of generating robust cortical modulation that was differentiable across attempted arm and hand movements of their paralyzed limb. Furthermore, all subjects were capable of voluntarily modulating this activity to control movement of a computer cursor with up to three degrees of freedom using the somatotopic control strategy. Additionally, for those subjects with electrode coverage of somatosensory cortex, we found that somatosensory cortex was capable of supporting ECoG-based BCI control.

Significance: These results demonstrate the feasibility of ECoG-based BCI systems for individuals with paralysis as well as highlight some of the key challenges that must be overcome before such systems are translated to the clinical realm. ClinicalTrials.gov Identifier: NCT01393444.
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http://dx.doi.org/10.1088/1741-2552/aa9bfbDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841472PMC
April 2018

Posterior Communicating Artery Giving Rise to Shared-Origin Anterior Choroidal Artery: Case Illustration.

World Neurosurg 2018 Jan 15;109:413-415. Epub 2017 Nov 15.

Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Background: The origin point of the anterior choroidal artery (AChA) is variable, typically arising from the supraclinoid internal carotid artery (ICA) distal to the posterior communicating artery (PComA) on either the posterolateral or posterior aspect of the ICA. Variations of AChA origin have important clinical implications, and rare origins reported previously include the ICA bifurcation and middle cerebral artery. We provide illustrations of a case of a shared-origin PComA and AChA.

Case Description: A young girl presented with intracranial hemorrhage and underwent angiography to evaluate for an underlying cause. Ultimately, 3-dimensional rotational angiography incidentally demonstrated a common origin of the AChA with the PComA.

Conclusions: A rare case of a shared-origin AChA and PComA is reported for angiographic illustration. The radiologic findings, embryology behind the development of the AChA, and neurosurgical and neurovascular relevance of this variant are discussed. The importance of recognizing the origin of the AChA is emphasized.
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http://dx.doi.org/10.1016/j.wneu.2017.10.098DOI Listing
January 2018

Sensorimotor experience and verb-category mapping in human sensory, motor and parietal neurons.

Cortex 2017 07 6;92:304-319. Epub 2017 May 6.

Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for the Neural Basis of Cognition, Pittsburgh, PA, USA; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA; Barnes-Jewish Hospital, St. Louis, MO, USA. Electronic address:

Semantic grounding is the process of relating meaning to symbols (e.g., words). It is the foundation for creating a representational symbolic system such as language. Semantic grounding for verb meaning is hypothesized to be achieved through two mechanisms: sensorimotor mapping, i.e., directly encoding the sensorimotor experiences the verb describes, and verb-category mapping, i.e., encoding the abstract category a verb belongs to. These two mechanisms were investigated by examining neuronal-level spike (i.e. neuronal action potential) activities from the motor, somatosensory and parietal areas in two human participants. Motor and a portion of somatosensory neurons were found to be involved in primarily sensorimotor mapping, while parietal and some somatosensory neurons were found to be involved in both sensorimotor and verb-category mapping. The time course of the spike activities and the selective tuning pattern of these neurons indicate that they belong to a large neural network used for semantic processing. This study is the first step towards understanding how words are processed by neurons.
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http://dx.doi.org/10.1016/j.cortex.2017.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543720PMC
July 2017

Human perception of electrical stimulation on the surface of somatosensory cortex.

PLoS One 2017 10;12(5):e0176020. Epub 2017 May 10.

Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Recent advancement in electrocorticography (ECoG)-based brain-computer interface technology has sparked a new interest in providing somatosensory feedback using ECoG electrodes, i.e., cortical surface electrodes. We conducted a 28-day study of cortical surface stimulation in an individual with arm paralysis due to brachial plexus injury to examine the sensation produced by electrical stimulation of the somatosensory cortex. A high-density ECoG grid was implanted over the somatosensory and motor cortices. Stimulation through cortical surface electrodes over the somatosensory cortex successfully elicited arm and hand sensations in our participant with chronic paralysis. There were three key findings. First, the intensity of perceived sensation increased monotonically with both pulse amplitude and pulse frequency. Second, changing pulse width changed the type of sensation based on qualitative description provided by the human participant. Third, the participant could distinguish between stimulation applied to two neighboring cortical surface electrodes, 4.5 mm center-to-center distance, for three out of seven electrode pairs tested. Taken together, we found that it was possible to modulate sensation intensity, sensation type, and evoke sensations across a range of locations from the fingers to the upper arm using different stimulation electrodes even in an individual with chronic impairment of somatosensory function. These three features are essential to provide effective somatosensory feedback for neuroprosthetic applications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176020PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425101PMC
September 2017

Absent pedicles in campomelic dysplasia.

Childs Nerv Syst 2017 Jun 26;33(6):987-992. Epub 2017 Apr 26.

Neurological Surgery, Bioengineering and Physical Medicine and Rehabilitation, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.

Objectives: The objective of the present study is to report a case of campomelic dysplasia illustrating the absence of cervical and thoracic pedicles. This report reiterates the importance of this clinical peculiarity in the setting of spine instrumentation.

Materials And Methods: A 10-year-old female patient with campomelic dysplasia presented with progressive kyphoscoliosis and signs of neural compromise. Imaging studies confirmed thoracic level stenosis and demonstrated absence of multiple pedicles in cervical and thoracic spine. The patient underwent decompression and instrumentation/fusion for her spinal deformity.

Results: The patient was instrumented between C2 and L4 with pedicle screws and sublaminar cables. However, pedicle fixation was not possible for the lower cervical and upper-mid thoracic spine. Also, floating posterior elements precluded the use of laminar fixation in the lower cervical spine. Cervicothoracic lumbosacral orthosis (CTLSO) was used for external immobilization to supplement the tenuous fixation in the cervicothoracic area. The patient improved neurologically with no signs of implant failure at the 2-year follow-up.

Conclusions: Absence of pedicles and floating posterior elements present a challenge during spine surgery in campomelic dysplasia. Surgeons should prepare for alternative fixation methods and external immobilization when planning on spinal instrumentation in affected patients.

Level Of Evidence: Level IV Case Report.
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http://dx.doi.org/10.1007/s00381-017-3375-4DOI Listing
June 2017

A Pediatric Tumor Found Frequently in the Adult Population: A Case of Anaplastic Astroblastoma in an Elderly Patient and Review of the Literature.

Case Rep Neurol Med 2017 23;2017:1607915. Epub 2017 Jan 23.

Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, PA, USA.

Astroblastomas are rare, potentially curable primary brain tumors which can be difficult to diagnose. We present the case of astroblastoma in a 73-year-old male, an atypical age for this tumor, more classically found in pediatric and young adult populations. Through our case and review of the literature, we note that this tumor is frequently reported in adult populations and the presentation of this tumor in the elderly is well described. This tumor is an important consideration in the differential diagnosis when managing both pediatric and adult patients of any age who present with the imaging findings characteristic of this rare tumor.
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http://dx.doi.org/10.1155/2017/1607915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292372PMC
January 2017

Risk factors for cerebrospinal fluid leak in pediatric patients undergoing endoscopic endonasal skull base surgery.

Int J Pediatr Otorhinolaryngol 2017 Feb 26;93:163-166. Epub 2016 Dec 26.

Department of Otolaryngology Head and Neck Surgery, University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh of UPMC, United States.

Objectives: To determine the risk factors associated with cerebrospinal fluid (CSF) leak following endoscopic endonasal surgery (EES) for pediatric skull base lesions.

Methods: Retrospective chart review of pediatric patients (ages 1 month to 18 years) treated for skull base lesions with EES from 1999 to 2014. Five pathologies were reviewed: craniopharyngioma, clival chordoma, pituitary adenoma, pituitary carcinoma, and Rathke's cleft cyst. Fisher's exact tests were used to evaluate the different factors to determine which had a statistically higher risk of leading to a post-operative CSF leak.

Results: 55 pediatric patients were identified who underwent 70 EES's for tumor resection. Of the 70 surgeries, 47 surgeries had intraoperative CSF leaks that were repaired at the time of surgery. 11 of 47 (23%) surgeries had post-operative CSF leaks that required secondary operative repair. Clival chordomas had the highest CSF leak rate at 36%. There was no statistical difference in leak rate based on the type of reconstruction, although 28% of cases that used a vascularized flap had a post-operative leak, whereas only 9% of those cases not using a vascularized flap had a leak. Post-operative hydrocephalus and perioperative use of a lumbar drain were not significant risk factors.

Conclusions: Pediatric patients with an intra-operative CSF leak during EES of the skull base have a high rate of post-operative CSF leaks. Clival chordomas appear to be a particularly high-risk group. The use of vascularized flaps and perioperative lumbar drains did not statistically decrease the rate of post-operative CSF leak.
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http://dx.doi.org/10.1016/j.ijporl.2016.12.019DOI Listing
February 2017

The Burden of Ionizing Radiation Studies in Children with Ventricular Shunts.

J Pediatr 2017 03 15;182:210-216.e1. Epub 2016 Dec 15.

Department of Pediatrics, Division of Pediatric Emergency Medicine and Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objectives: To quantify the number of shunt-related imaging studies that patients with ventricular shunts undergo and to calculate the proportion of computed tomography (CT) scans associated with a surgical intervention.

Study Design: Retrospective longitudinal cohort analysis of patients up to age 22 years with a shunt placed January 2002 through December 2003 at a pediatric hospital. Primary outcome was the number of head CT scans, shunt series radiograph, skull radiographs, nuclear medicine, and brain magnetic resonance imaging studies for 10 years following shunt placement. Secondary outcome was surgical interventions performed within 7 days of a head CT. Descriptive statistics were used for analysis.

Results: Patients (n = 130) followed over 10 years comprised the study cohort. The most common reasons for shunt placement were congenital hydrocephalus (30%), obstructive hydrocephalus (19%), and atraumatic hemorrhage (18%), and 97% of shunts were ventriculoperitoneal. Patients underwent a median of 8.5 head CTs, 3.0 shunt series radiographs, 1.0 skull radiographs, 0 nuclear medicine studies, and 1.0 brain magnetic resonance imaging scans over the 10 years following shunt placement. The frequency of head CT scans was greatest in the first year after shunt placement (median 2.0 CTs). Of 1411 head CTs in the cohort, 237 resulted in surgical intervention within 7 days (17%, 95% CI 15%-19%).

Conclusions: Children with ventricular shunts have been exposed to large numbers of imaging studies that deliver radiation and most do not result in a surgical procedure. This suggests a need to improve the process of evaluating for ventricular shunt malfunction and minimize radiation exposure.
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http://dx.doi.org/10.1016/j.jpeds.2016.11.051DOI Listing
March 2017

Intracortical microstimulation of human somatosensory cortex.

Sci Transl Med 2016 10 13;8(361):361ra141. Epub 2016 Oct 13.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Intracortical microstimulation of the somatosensory cortex offers the potential for creating a sensory neuroprosthesis to restore tactile sensation. Whereas animal studies have suggested that both cutaneous and proprioceptive percepts can be evoked using this approach, the perceptual quality of the stimuli cannot be measured in these experiments. We show that microstimulation within the hand area of the somatosensory cortex of a person with long-term spinal cord injury evokes tactile sensations perceived as originating from locations on the hand and that cortical stimulation sites are organized according to expected somatotopic principles. Many of these percepts exhibit naturalistic characteristics (including feelings of pressure), can be evoked at low stimulation amplitudes, and remain stable for months. Further, modulating the stimulus amplitude grades the perceptual intensity of the stimuli, suggesting that intracortical microstimulation could be used to convey information about the contact location and pressure necessary to perform dexterous hand movements associated with object manipulation.
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http://dx.doi.org/10.1126/scitranslmed.aaf8083DOI Listing
October 2016

Visual Outcomes after Endoscopic Endonasal Approach for Craniopharyngioma: The Pittsburgh Experience.

J Neurol Surg B Skull Base 2016 Aug 9;77(4):326-32. Epub 2016 Feb 9.

UPMC Department of Neurosurgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.

This series of patients has been published in the neurosurgical literature earlier this year, detailing multiple aspects of both the surgical technique and postoperative outcomes. Our aim in this series is not to revisit all the aspects of this publication, but rather to analyze more specifically the benefits of this procedure as it pertains to the preservation of neurological structures of vision-specifically the optic chiasm-and provide a more detailed analysis of visual outcomes in these patients.
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http://dx.doi.org/10.1055/s-0036-1571333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949065PMC
August 2016

Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate.

J Neural Eng 2016 08 28;13(4):046019. Epub 2016 Jun 28.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. Center for the Neural Basis of Cognition, Pittsburgh, PA, USA. Systems Neuroscience Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Objective: Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue.

Approach: We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d.

Main Results: Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation.

Significance: These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.
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http://dx.doi.org/10.1088/1741-2560/13/4/046019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993459PMC
August 2016

Validation of the Pittsburgh Infant Brain Injury Score for Abusive Head Trauma.

Pediatrics 2016 07 23;138(1). Epub 2016 Jun 23.

Safar Center for Resuscitation Research, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;

Background: Abusive head trauma is the leading cause of death from physical abuse. Misdiagnosis of abusive head trauma as well as other types of brain abnormalities in infants is common and contributes to increased morbidity and mortality. We previously derived the Pittsburgh Infant Brain Injury Score (PIBIS), a clinical prediction rule to assist physicians deciding which high-risk infants should undergo computed tomography of the head.

Methods: Well-appearing infants 30 to 364 days of age with temperature <38.3°C, no history of trauma, and a symptom associated with an increased risk of having a brain abnormality were eligible for enrollment in this prospective, multicenter clinical prediction rule validation. By using a predefined neuroimaging paradigm, subjects were classified as cases or controls. The sensitivity, specificity, and negative and positive predictive values of the rule for prediction of brain injury were calculated.

Results: A total of 1040 infants were enrolled: 214 cases and 826 controls. The 5-point PIBIS included abnormality on dermatologic examination (2 points), age ≥3.0 months (1 point), head circumference >85th percentile (1 point), and serum hemoglobin <11.2g/dL (1 point). At a score of 2, the sensitivity and specificity for abnormal neuroimaging was 93.3% (95% confidence interval 89.0%-96.3%) and 53% (95% confidence interval 49.3%-57.1%), respectively.

Conclusions: Our data suggest that the PIBIS accurately identifies infants who would benefit from neuroimaging to evaluate for brain injury. An implementation analysis is needed before the PIBIS can be integrated into clinical practice.
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http://dx.doi.org/10.1542/peds.2015-3756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925074PMC
July 2016