Publications by authors named "Adam J Kundishora"

45 Publications

Genomics of human congenital hydrocephalus.

Childs Nerv Syst 2021 Jul 7. Epub 2021 Jul 7.

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of pathological cerebrospinal fluid (CSF) accumulation and, therefore, treated largely by neurosurgical CSF diversion. The persistence of ventriculomegaly and poor neurodevelopmental outcomes in some post-surgical patients highlights our limited knowledge of disease mechanisms. Recent whole-exome sequencing (WES) studies have shown that rare, damaging de novo and inherited mutations with large effect contribute to ~ 25% of sporadic CH. Interestingly, multiple CH genes are key regulators of neural stem cell growth and differentiation and converge in human transcriptional networks and cell types pertinent to fetal neurogliogenesis. These data implicate genetic disruption of early brain development as the primary pathomechanism in a substantial minority of patients with sporadic CH, shedding new light on human brain development and the pathogenesis of hydrocephalus. These data further suggest WES as a clinical tool with potential to re-classify CH according to a molecular nomenclature of increased precision and utility for genetic counseling, outcome prognostication, and treatment stratification.
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http://dx.doi.org/10.1007/s00381-021-05230-8DOI Listing
July 2021

DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.

JAMA Neurol 2021 Jun 14. Epub 2021 Jun 14.

Yale Center for Genome Analysis, West Haven, Connecticut.

Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals.

Objective: To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk.

Design, Setting, And Participants: A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants who met criteria and were presented with the option to join the study agreed to do so; none were excluded. Twenty-four probands (22 trios and 2 singletons) composed the discovery cohort, and 84 probands (29 trios and 55 singletons) composed the validation cohort.

Main Outcomes And Measures: Gene variants were identified and filtered using stringent criteria. Enrichment and case-control tests assessed gene-level variant burden. In silico modeling estimated the probability of variant association with protein structure. Integrative genomics assessed expression patterns of MMD risk genes derived from single-cell RNA sequencing data of human and mouse brain tissue.

Results: Of the 24 patients in the discovery cohort, 14 (58.3%) were men and 18 (75.0%) were of European ancestry. Three of 24 discovery cohort probands contained 2 do novo (1-tailed Poisson P = 1.1 × 10-6) and 1 rare, transmitted damaging variant (12.5% of cases) in DIAPH1 (mammalian diaphanous-1), a key regulator of actin remodeling in vascular cells and platelets. Four additional ultrarare damaging heterozygous DIAPH1 variants (3 unphased) were identified in 3 other patients in an 84-proband validation cohort (73.8% female, 77.4% European). All 6 patients were non-East Asian. Compound heterozygous variants were identified in ena/vasodilator-stimulated phosphoproteinlike protein EVL, a mammalian diaphanous-1 interactor that regulates actin polymerization. DIAPH1 and EVL mutant probands had severe, bilateral MMD associated with transfusion-dependent thrombocytopenia. DIAPH1 and other MMD risk genes are enriched in mural cells of midgestational human brain. The DIAPH1 coexpression network converges in vascular cell actin cytoskeleton regulatory pathways.

Conclusions And Relevance: These findings provide the largest collection to date of non-East Asian individuals with sporadic MMD harboring pathogenic variants in the same gene. The results suggest that DIAPH1 is a novel MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis, with diagnostic and therapeutic ramifications.
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http://dx.doi.org/10.1001/jamaneurol.2021.1681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204259PMC
June 2021

Impact of race on outcomes and healthcare utilization following spinal fusion for adolescent idiopathic scoliosis.

Clin Neurol Neurosurg 2021 Jul 4;206:106634. Epub 2021 May 4.

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA. Electronic address:

Objectives: Racial disparities in spine surgery have been shown to impact surgical management and postoperative complications. However, for adolescent patients with idiopathic scoliosis (AIS) treated by posterior spinal fusion (PSF), the influence of race on postoperative outcomes remains unclear. The aim of the study was to investigate the differences in baseline patient demographics, inpatient management, and postoperative complications for adolescents with AIS undergoing elective, posterior spinal surgery (≥ 4 levels).

Patients And Methods: The Kids' Inpatient Database year 2012 was queried. Adolescent patients (age 10-17 years old) with AIS undergoing elective, PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were divided into 4 cohorts: Black, White, Hispanic, and Other. Patient demographics, comorbidities, complications, length of hospital stay (LOS), discharge disposition and total cost were recorded. The primary outcome was the rate of intraoperative and postoperative complications and resource utilization after elective PSF intervention.

Results: Patient demographics significantly differed between the four cohorts. While age was similar (p = 0.288), the White cohort had a greater proportion of female patients (White: 79.0%; Black: 72.1%; Hispanic: 78.2%; Other: 75.9%, p = 0.006), and the Black cohort had the largest proportion of patients in the 0-25th income quartile (White: 16.1%; Black: 43.3%; Hispanic: 28.0%; Other: 15.3%, p < 0.001). There were significant differences in hospital region (p < 0.001) and bed size (p < 0.001) between the cohorts, with more Hispanic adolescents being treated in the West (White: 21.9%; Black: 8.9%; Hispanic: 40.3%; Other: 29.3%) at small hospitals (White: 14.0%; Black: 13.9%; Hispanic: 16.2%; Other: 7.1%). Baseline comorbidities were similar between the cohorts. The use of blood transfusions was significantly greater in the Black cohort compared to the other racial groups (White: 16.7%; Black: 25.0%; Hispanic: 24.5%; Other: 22.7%, p < 0.001). The number of vertebral levels involved differed significantly between the cohorts (p < 0.001), with the majority of patients having 9-levels or greater involved (White: 80.9%; Black: 81.7%; Hispanic: 84.3%; Other: 67.3%). The rate of complications encountered during admission was greatest in the Other cohort (White: 21.9%; Black: 23.6%; Hispanic: 22.2%; Other: 34.9%, p < 0.001). While LOS was similar between the cohorts (p = 0.702), median total cost of admission was highest for Hispanic patients (White: $49,340 [37,908-65,078]; Black: $47,787 [37,718-64,670]; Hispanic: $54,718 [40,689-69,266]; Other: $54,110 [41,292-71,540], p < 0.001).

Conclusions: Our study suggests that race may not have a significant impact on surgical outcomes after elective posterior spine surgery for adolescent idiopathic scoliosis. Further studies are necessary to corroborate our findings.
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http://dx.doi.org/10.1016/j.clineuro.2021.106634DOI Listing
July 2021

Somatic NF1 mutations in pituitary adenomas: Report of two cases.

Cancer Genet 2021 Aug 2;256-257:26-30. Epub 2021 Apr 2.

Department of Neurosurgery, Yale School of Medicine, 20 York Street, LCI8, New Haven, CT 06511, United States. Electronic address:

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http://dx.doi.org/10.1016/j.cancergen.2021.03.004DOI Listing
August 2021

Post-traumatic seizures following pediatric traumatic brain injury.

Clin Neurol Neurosurg 2021 Apr 10;203:106556. Epub 2021 Feb 10.

Department of Neurosurgery, Yale University School of Medicine, New Haven, 06520, CT, United States. Electronic address:

Objectives: The aim of this study was to investigate the national impact of demographic, hospital, and inpatient risk factors on post-traumatic seizure (PTS) development in pediatric patients who presented to the ED following a traumatic brain injury (TBI).

Patients And Methods: The Nationwide Emergency Department Sample database years 2010-2014 was queried. Patients (<21 years old) with a primary diagnosis of TBI and subsequent secondary diagnosis of PTS were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. We identified demographic variables, hospital characteristics, pre-existing medical comorbidities, etiology of injuries, and type of injury. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with post-traumatic seizures.

Results: We identified 1,244,087 patients who sustained TBI, of which 10,340 (0.83%) developed PTS. Of the patients who had seizures, the youngest cohort aged 0-5 years had the greatest proportion of seizure development (p < 0.001). Compared to those TBI patients with loss of consciousness (LOC), patients encountering no LOC after TBI had the smallest proportion of seizures while Prolonged LOC with baseline return had the greatest proportion. On univariate analysis of the effect of in-hospital complication on rate of seizures, respiratory, renal and urinary, hematoma, septicemia, and other neurological complications were all significantly associated with seizure development. On multivariate regression, age 6-10 years (OR: 0.48, p < 0.001) 11-15 years (OR: 0.41, p < 0.001), and 16-20 years (OR: 0.51, p < 0.001) were independently associated with decreased risk of developing seizures. Extended LOC with baseline return (OR: 6.33, p < 0.001), extended LOC without baseline return (OR: 1.95, p = 0.009), and Other LOC (OR: 3.02, p < 0.001) were independently associated with increased risk of developing seizures. Subarachnoid hemorrhage (OR: 4.14, p < 0.001), subdural hemorrhage [OR: 7.72, p < 0.001), and extradural hemorrhage (OR: 3.13, p < 0.001) were all independently associated with increased risk of developing seizures.

Conclusion: Out study demonstrates that various demographic, hospital, and clinical risk factors are associated with the development of seizures following traumatic brain injury. Enhancing awareness of these drivers may help provide greater awareness of patients likely to develop post-traumatic seizures such that this complication can be decreased in incidence so as to improve quality of care and decrease healthcare costs.
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http://dx.doi.org/10.1016/j.clineuro.2021.106556DOI Listing
April 2021

Hypermutated phenotype in gliosarcoma of the spinal cord.

NPJ Precis Oncol 2021 Feb 12;5(1). Epub 2021 Feb 12.

Department of Neurosurgery, Yale School of Medicine, New Haven, CT, 06511, USA.

Gliosarcoma is a variant of glioblastoma with equally poor prognosis and characterized by mixed glial and mesenchymal pathology. Metastasis is not uncommon but the involvement of the spinal cord is rare, and comprehensive genetic characterization of spinal gliosarcoma is lacking. We describe a patient initially diagnosed with a low-grade brain glioma via biopsy, followed by adjuvant radiation and temozolomide treatment. Nearly 2 years after diagnosis, she developed neurological deficits from an intradural, extramedullary tumor anterior to the spinal cord at T4, which was resected and diagnosed as gliosarcoma. Whole-exome sequencing (WES) of this tumor revealed a hypermutated phenotype, characterized by somatic mutations in key DNA mismatch repair (MMR) pathway genes, an abundance of C>T transitions within the identified somatic single nucleotide variations, and microsatellite stability, together consistent with temozolomide-mediated hypermutagenesis. This is the first report of a hypermutator phenotype in gliosarcoma, which may represent a novel genomic mechanism of progression from lower grade glioma.
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http://dx.doi.org/10.1038/s41698-021-00143-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881101PMC
February 2021

The Effects of Pulmonary Risk Factors on Hospital Resource Use After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis Correction.

World Neurosurg 2021 May 3;149:e737-e747. Epub 2021 Feb 3.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: The aim of this study was to determine the impact of preoperative pulmonary risk factors (PRFS) on surgical outcomes after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS).

Methods: A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database from 2016 to 2018. All pediatric patients with AIS undergoing PSF were identified. Patients were then categorized by whether they had recorded baseline PRF or no-PRF. Patient demographics, comorbidities, intraoperative variables, complications, length of stay, discharge disposition, and readmission rate were assessed.

Results: A total of 4929 patients were identified, of whom 280 (5.7%) had baseline PRF. Compared with the no-PRF cohort, the PRF cohort had higher rates of complications (PRF, 4.3% vs. no-PRF, 2.2%; P = 0.03) and longer hospital stays (PRF, 4.6 ± 4.3 days vs. no-PRF, 3.8 ± 2.3 days; P < 0.001), yet, discharge disposition was similar between cohorts (P = 0.70). Rates of 30-day unplanned readmission were significantly higher in the PRF cohort (PRF, 6.3% vs. no-PRF, 2.7%; P = 0.009), yet, days to readmission (P = 0.76) and rates of 30-day reoperation (P = 0.16) were similar between cohorts. On multivariate analysis, PRF was found to be a significant independent risk factor for longer hospital stays (risk ratio, 0.74; 95% confidence interval, 0.44-1.04; P < 0.001) but not postoperative complication or 30-day unplanned readmission.

Conclusions: Our study showed that PRF may be a risk factor for slightly longer hospital stays without higher rates of complication or unplanned readmission for patients with AIS undergoing PSF and thus should not preclude surgical management.
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http://dx.doi.org/10.1016/j.wneu.2021.01.109DOI Listing
May 2021

Thirty- and 90-day Readmissions After Spinal Surgery for Spine Metastases: A National Trend Analysis of 4423 Patients.

Spine (Phila Pa 1976) 2021 Jun;46(12):828-835

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT.

Study Design: Retrospective cohort study.

Objective: The aim of this study was to investigate differences in 30- and 90-day readmissions for spine metastases treated with decompression and/or fusion spine surgery in a nationwide readmission database.

Summary Of Background Data: Patients with metastases to the spine represent a particularly vulnerable patient group that may encounter frequent readmissions. However, the 30- and 90-day rates for readmission following surgery for spine metastases have not been well described.

Methods: The Nationwide Readmission Database years 2013 to 2015 was queried. Patients were grouped by no readmission (non-R), readmission within 30 days (30-R), and readmission within 31 to 90 days (90-R). Weighted multivariate analysis assessed impact of treatment approach and clinical factors associated with 30- and 90-day readmissions.

Results: There were a total of 4423 patients with a diagnosis of spine metastases identified who underwent spine surgery, of which 1657 (37.5%) encountered either a 30-or 90-day unplanned readmission (30-R: n = 1068 [24-.1%]; 90-R: n = 589 [13.3%]; non-R: n = 2766). The most prevalent inpatient complications observed were postoperative infection (30-R: 16.3%, 90-R: 14.3%, non-R: 11.5%), acute post-hemorrhagic anemia (30-R: 13.4%, 90-R: 14.2%, non-R: 14.5%), and genitourinary complication (30-R: 5.7%, 90-R: 2.9%, non-R: 6.2%). The most prevalent 30-day and 90-day reasons for admission were sepsis (30-R: 10.2%, 90-R: 10.8%), postoperative infection (30-R: 13.7%, 90-R: 6.5%), and genitourinary complication (30-R: 3.9%, 90-R: 4.1%). On multivariate regression analysis, surgery type, age, hypertension, and renal failure were independently associated with 30-day readmission; rheumatoid arthritis/collagen vascular diseases, and coagulopathy were independently associated with 90-day readmission.

Conclusion: In this study, we demonstrate several patient-level factors independently associated with unplanned hospital readmissions after surgical treatment intervention for spine metastases. Furthermore, we find that the most common reasons for readmission are sepsis, postoperative infection, and genitourinary complications.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278805PMC
June 2021

Case Report: Suprasellar Pituitary Adenoma Presenting With Temporal Lobe Seizures.

Front Surg 2020 1;7:598138. Epub 2020 Dec 1.

Department of Neurosurgery, Yale School of Medicine, New Haven, CT, United States.

Seizures in patients with pituitary pathology are uncommon and typically secondary to electrolyte disturbances. Rarely, seizures have been described from mass effect related to large prolactinomas undergoing medical treatment. We describe a 54 year-old male who presented with a first-time generalized seizure, secondary to a pituitary macroadenoma compressing the left temporal lobe. His seizures abated after endoscopic endonasal debulking of the tumor. This report highlights isolated seizures as a potential sole presenting symptom of pituitary macroadenomas without visual or endocrine dysfunction. Prompt surgical debulking to relieve mass effect on the temporal lobe may effectively prevent further seizure activity.
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http://dx.doi.org/10.3389/fsurg.2020.598138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736041PMC
December 2020

Genetic characterization of a case of sellar metastasis from bronchial carcinoid neuroendocrine tumor.

Surg Neurol Int 2020 25;11:303. Epub 2020 Sep 25.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, United States.

Background: Metastasis to the pituitary gland from neuroendocrine tumors is a rare occurrence that may originate from primary tumors the lung, gastrointestinal tract, thyroid, and pancreas, among others. Patients may present with signs of endocrine dysfunction secondary to pituitary involvement, as well as mass effect-related symptoms including headaches and visual deficits. Despite a small but accumulating body of literature describing the clinical and histopathological correlates for pituitary metastases from neuroendocrine tumors, the genetic basis underlying this presentation remains poorly characterized.

Case Description: We report the case of a 68-year-old with a history of lung carcinoid tumor who developed a suprasellar lesion, causing mild visual deficits but otherwise without clinical or biochemical endocrine abnormalities. She underwent endoscopic endonasal resection of her tumor with final pathology confirming metastasis from her original neuroendocrine tumor. Whole-exome sequencing was performed on the resected sellar tumor and matching blood, revealing increased genomic instability and key mutations in and that have been previously implicated in both systemic neuroendocrine and primary pituitary tumors with potentially actionable therapeutic targets.

Conclusion: This is the first genomic characterization of a metastatic tumor to the sella and reports potential genetic insight, implicating and mutations, into the pathophysiology of sellar metastasis from primary systemic tumors.
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http://dx.doi.org/10.25259/SNI_265_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568119PMC
September 2020

Impact of Preoperative Anemia on Outcomes After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

World Neurosurg 2021 02 19;146:e214-e224. Epub 2020 Oct 19.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: The aim of this study was to investigate the relationship of preoperative anemia and outcomes after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS).

Methods: A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database from 2016 to 2018. All pediatric patients (age 10-18 years) with AIS undergoing PSF were identified. Two cohorts were categorized into anemic and nonanemic cohorts based on age-based and sex-based criteria for anemia. Thirty-day outcomes and readmission rates were evaluated.

Results: A total of 4929 patients were identified, of whom 592 (12.0%) were found to have preoperative anemia. The anemic cohort had a greater prevalence of comorbidities and longer operative times. Compared with the nonanemic cohort, the anemic cohort experienced significantly higher rates of perioperative bleed/transfusion (nonanemic, 67.4% vs. anemic, 73.5%; P = 0.004) and required a greater total amount of blood transfused (nonanemic, 283.2 ± 265.5 mL vs. anemic, 386.7 ± 342.6 mL; P < 0.001). The anemic cohort experienced significantly longer hospital stays (nonanemic, 3.8 ± 2.2 days vs. anemic, 4.2 ± 3.9 days; P = 0.001), yet discharge disposition (P = 0.58), 30-day complication rates (P = 0.79) and unplanned reoperation rates (P = 0.90) were similar between cohorts. On multivariate analysis, anemia was found to be an independent predictor of perioperative bleed/transfusion (odds ratio, 1.36; 95% confidence interval, 1.12-1.66; P = 0.002) as well as a longer length of hospital stay (relative risk, 0.46; 95% confidence interval, 0.25-0.67; P < 0.001) but was not an independent predictor for postoperative complications (P = 0.85).

Conclusions: Our study suggests that preoperative anemia may be a risk factor for a greater perioperative bleed/transfusion event and slightly longer length of stay; however, it was not associated with greater 30-day complication and readmission rates in patients with AIS undergoing PSF.
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http://dx.doi.org/10.1016/j.wneu.2020.10.074DOI Listing
February 2021

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

iScience 2020 Oct 11;23(10):101552. Epub 2020 Sep 11.

Yale Center for Genome Analysis, West Haven, CT, USA.

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated mutation (p.Cys188Trp) in the GABA receptor Cl channel γ-1 subunit () exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na and Ca channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca channel Ca3.2 (). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.
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http://dx.doi.org/10.1016/j.isci.2020.101552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554653PMC
October 2020

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.

Nat Med 2020 11 19;26(11):1754-1765. Epub 2020 Oct 19.

Departments of Neurosurgery, Engineering Science & Mechanics, and Physics; Center for Neural Engineering and Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA, USA.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
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http://dx.doi.org/10.1038/s41591-020-1090-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871900PMC
November 2020

Laser interstitial thermal therapy in neuro-oncology applications.

Surg Neurol Int 2020 8;11:231. Epub 2020 Aug 8.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, United States.

Background: Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment for multiple intracranial pathologies that are of growing interest to neurosurgeons and their patients and is emerging as an effective alternative to standard of care open surgery in the neurosurgical armamentarium. This option was initially considered for those patients with medical comorbidities and lesion-specific characteristics that confer excessively high risk for resection through a standard craniotomy approach but indications are changing.

Methods: The PubMed database was searched for studies in the English literature on LITT for the treatment of primary and metastatic brain tumors, meningiomas, as well as for radiation necrosis (RN) in previously irradiated brain tumors.

Results: This review provides an update of the relevant literature regarding application of LITT in neurosurgical oncology for the treatment of and recurrent primary gliomas and brain metastases radiographically regrowing after previous irradiation as recurrent tumor or RN. In addition, this review details the limited experience of LITT with meningiomas and symptomatic peritumoral edema after radiosurgery. The advantages and disadvantages, indications, and comparisons to standard of care treatments such as craniotomy for open surgical resection are discussed for each pathology. Finally, the literature on cost-benefit analyses for LITT are reviewed.

Conclusion: The studies discussed in this review have helped define the role of LITT in neurosurgical oncology and delineate optimal patient selection and tumor characteristics most suitable to this intervention.
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http://dx.doi.org/10.25259/SNI_496_2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451173PMC
August 2020

Thalamic Stimulation Improves Postictal Cortical Arousal and Behavior.

J Neurosci 2020 09 21;40(38):7343-7354. Epub 2020 Aug 21.

Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520

The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy. The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.
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http://dx.doi.org/10.1523/JNEUROSCI.1370-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534908PMC
September 2020

Laser interstitial thermal therapy for treatment of cerebral radiation necrosis.

Int J Hyperthermia 2020 07;37(2):68-76

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.

Radiation necrosis is a well described complication after radiosurgical treatment of intracranial pathologies - best recognized after the treatment of patients with arteriovenous malformations and brain metastases but possibly also affecting patients treated with radiosurgery for meningioma. The pathophysiology of radiation necrosis is still not well understood but is most likely a secondary local tissue inflammatory response to brain tissue injured by radiation. Radiation necrosis in brain metastases patients may present radiographically and behave clinically like recurrent tumor. Differentiation between radiation necrosis and recurrent tumor has been difficult based on radiographic changes alone. Biopsy or craniotomy therefore remains the gold standard method of diagnosis. For symptomatic patients, corticosteroids are first-line therapy, but patients may fail medical management due to intolerance of chronic steroids or persistence of symptoms. In these cases, open surgical resection has been shown to be successful in management of surgically amenable lesions but may be suboptimal in patients with deep-seated lesions or extensive prior cranial surgical history, both carrying high risk for peri-operative morbidity. Laser interstitial thermal therapy has emerged as a viable, alternative surgical option. In addition to allowing access to tissue for diagnosis, thermal treatment of the lesion can also be delivered precisely and accurately under real-time imaging guidance. This review highlights the pertinent studies that have shaped the impetus for use of laser interstitial thermal therapy in the treatment of radiation necrosis, reviewing indications, outcomes, and nuances toward successful application of this technology in patients with suspected radiation necrosis.
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http://dx.doi.org/10.1080/02656736.2020.1760362DOI Listing
July 2020

Comparison of epidemiology, treatments, and outcomes in pediatric versus adult ependymoma.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa019. Epub 2020 Feb 21.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

Background: Mounting evidence supports the presence of heterogeneity in the presentation of ependymoma patients with respect to location, histopathology, and behavior between pediatric and adult patients. However, the influence of age on treatment outcomes in ependymoma remains obscure.

Methods: The SEER database years 1975-2016 were queried. Patients with a diagnosis of ependymoma were identified using the International Classification of Diseases for Oncology, Third Edition, coding system. Patients were classified into one of 4 age groups: children (age 0-12 years), adolescents (age 13-21 years), young adults (age 22-45 years), and older adults (age >45 years). The weighed multivariate analysis assessed the impact of age on survival outcomes following surgical treatment.

Results: There were a total of 6076 patients identified with ependymoma, of which 1111 (18%) were children, 529 (9%) were adolescents, 2039 (34%) were young adults, and 2397 (40%) were older adults. There were statistically significant differences between cohorts with respect to race ( < .001), anatomical location ( < .001), extent of resection ( < .001), radiation use ( < .001), tumor grade ( < .001), histological classification ( < .001), and all-cause mortality ( < .001). There was no significant difference between cohorts with respect to gender ( = .103). On multivariate logistic regression, factors associated with all-cause mortality rates included males (vs females), supratentorial location (vs spinal cord tumors), and radiation treatment (vs no radiation).

Conclusions: Our study using the SEER database demonstrates the various demographic and treatment risk factors that are associated with increased rates of all-cause mortality between the pediatric and adult populations following a diagnosis of ependymoma.
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http://dx.doi.org/10.1093/noajnl/vdaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212900PMC
February 2020

Patient Risk Factors Associated With 30- and 90-Day Readmission After Cervical Discectomy: A Nationwide Readmission Database Study.

Clin Spine Surg 2020 11;33(9):E434-E441

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT.

Study Design: This is a retrospective cohort study.

Objective: The aim of this study was to assess the patient-level risk factors associated with 30- and 90-day unplanned readmissions following elective anterior cervical decompression and fusion (ACDF) or cervical disk arthroplasty (CDA).

Summary Of Background Data: For cervical disk pathology, both ACDF and CDA are increasingly performed nationwide. However, relatively little is known about the adverse complications and rates of readmission for ACDF and CDA.

Methods: A retrospective cohort study was performed using the Nationwide Readmission Database from the years 2013 to 2015. All patients undergoing either CDA or ACDF were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Unique patient linkage numbers were used to follow patients and to identify 30- and 31-90-day readmission rates. Patients were grouped by no readmission (Non-R), readmission within 30 days (30-R), and readmission within 31-90 days (90-R).

Results: There were a total of 13,093 index admissions with 856 (6.5%) readmissions [30-R: n=532 (4.0%); 90-R: n=324 (2.5%)]. Both overall length of stay and total cost were greater in the 30-R cohort compared with 90-R and Non-R cohorts. The most prevalent 30- and 90-day complications seen among the readmitted cohorts were infection, genitourinary complication, and device complication. On multivariate regression analysis, age, Medicaid status, medium and large hospital bed size, deficiency anemia, and any complication during index admission were independently associated with increased 30-day readmission. Whereas age, large hospital bed size, coagulopathy, and any complication during the initial hospitalization were independently associated with increased 90-day readmission.

Conclusion: Our nationwide study identifies the 30- and 90-day readmission rates and several patient-related risk factors associated with unplanned readmission after common anterior cervical spine procedures.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BSD.0000000000001030DOI Listing
November 2020

Persistent mutation despite multimodal therapy in recurrent pediatric glioblastoma.

NPJ Genom Med 2020 1;5:23. Epub 2020 Jun 1.

Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06511 USA.

Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently mutated clone, with rare mutations in and , the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the known underlying deficiency. As such, this case represents a novel report following the clinical and genetic progression of a mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for mutations in gliomagenesis and resistance to standard therapies.
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http://dx.doi.org/10.1038/s41525-020-0130-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264170PMC
June 2020

Pre-operative headaches and obstructive hydrocephalus predict an extended length of stay following suboccipital decompression for pediatric Chiari I malformation.

Childs Nerv Syst 2021 01 9;37(1):91-99. Epub 2020 Jun 9.

Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06520, USA.

Purpose: For young children and adolescents with Chiari malformation type I (CM-I), the determinants of extended length of hospital stay (LOS) after neurosurgical suboccipital decompression are obscure. Here, we investigate the impact of patient- and hospital-level risk factors on extended LOS following surgical decompression for CM-I in young children to adolescents.

Methods: The Kids' Inpatient Database year 2012 was queried. Pediatric CM-I patients (6-18 years) undergoing surgical decompression were identified. Weighted patient demographics, comorbidities, complications, LOS, disposition, and total cost were recorded. A multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree patient comorbidities or post-operative complications correlated with extended LOS.

Results: A total of 1592 pediatric CM-I patients were identified for which 328 (20.6%) patients had extended LOS (normal LOS, 1264; extended LOS, 328). Age, gender, race, median household income quartile, and healthcare coverage distributions were similar between the two cohorts. Patients with extended LOS had significantly greater admission comorbidities including headache symptoms, nausea and vomiting, obstructive hydrocephalus, lack of coordination, deficiency anemias, and fluid and electrolyte disorders. On multivariate logistic regression, several risk factors were associated with extended LOS, including headache symptoms, obstructive hydrocephalus, and fluid and electrolyte disorders.

Conclusions: Our study using the Kids' Inpatient Database demonstrates that presenting symptoms and signs, including headaches and obstructive hydrocephalus, respectively, are significantly associated with extended LOS following decompression for pediatric CM-I.
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http://dx.doi.org/10.1007/s00381-020-04688-2DOI Listing
January 2021

Associated risk factors for extended length of stay following anterior cervical discectomy and fusion for cervical spondylotic myelopathy.

Clin Neurol Neurosurg 2020 08 4;195:105883. Epub 2020 May 4.

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, United States.

Objectives: There is a paucity of literature describing the predictors associated with extended length of hospital stay (LOS) for patients undergoing anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy. The aim of this study was to identify the patient- and hospital-level factors associated with extended LOS for patients with cervical spondylotic myelopathy undergoing ACDF.

Patients And Methods: The National Inpatient Sample database was queried to identify patients with a diagnosis of cervical spondylotic myelopathy undergoing ACDF between 2010 and 2014. Updated trend weights were used to assess patient demographics, comorbidities, complications, LOS, discharge disposition and total cost. Multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree to which patient comorbidities or postoperative complications correlated with extended LOS (>3 days).

Results: We identified 144,514 patients with 29,947 (20.7%) experiencing an extended LOS (Normal LOS: 114,567; Extended LOS: 29,947). Comorbidities were overall significantly higher in the extended LOS cohort compared to the normal LOS cohort. Patients with extended LOS had a significantly greater proportion of blood transfusion (p < 0.001) and 2-3 vertebral levels fused (p < 0.001). The overall complication rates were greater in the extended LOS cohort (Normal LOS: 7.4% vs. Extended LOS: 44.8%, p < 0.001). The extended LOS cohort incurred $14,489 more in total cost (Normal LOS: $15,486 [11,787-20,623] vs. Extended LOS: $29,975 [21,286-45,285], p < 0.001) and had more patients discharged to non-routine locations (p < 0.001) compared to the normal LOS cohort. On multivariate logistic regression, several risk-factors were associated with extended LOS including: age, male gender, Black and Hispanic race, patient income, insurance, multiple comorbidities, blood transfusion, and number of complications. The odds ratio for extended LOS was 5.15 (95% CI: 4.68-5.67) for patients with 1 complication and 25.54 (95% CI: 20.54-31.75) for patients with >1 complication.

Conclusion: Our national cohort study demonstrated multiple patient- and hospital-level factors associated with extended LOS (>3 days) after ACDF for CSM. Specifically, patients with an extended LOS had lower socioeconomic status, higher rate of comorbidities, greater percentage of postoperative complications and non-routine discharges, with greater overall costs. Further investigational studies are necessary to identify quality improvement strategies targeted to better optimizing patients preoperatively and reducing perioperative complications in order to improve quality of patient care and reduce hospital LOS.
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http://dx.doi.org/10.1016/j.clineuro.2020.105883DOI Listing
August 2020

Risk Factors for the Development of Post-Traumatic Hydrocephalus in Children.

World Neurosurg 2020 09 7;141:e105-e111. Epub 2020 May 7.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: The aim of this study was to investigate the national impact of demographic, hospital, and inpatient risk factors on posttraumatic hydrocephalus (PTH) development in pediatric patients who presented to the emergency department after a traumatic brain injury (TBI).

Methods: The Nationwide Emergency Department Sample database 2010-2014 was queried. Patients (<21 years old) with a primary diagnosis of TBI and subsequent secondary diagnosis of PTH were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system.

Results: We identified 1,244,087 patients who sustained TBI, of whom 930 (0.07%) developed PTH. The rates of subdural hemorrhage and subarachnoid hemorrhage were both significantly higher for the PTH cohort. On multivariate regression, age 6-10 years (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.38-0.93; P = 0.022), 11-15 years (OR, 0.32; 95% CI, 0.21-0.48; P < 0.0001), and 16-20 years (OR, 0.24; 95% CI, 0.15-0.37; P < 0.0001) were independently associated with decreased risk of developing hydrocephalus, compared with ages 0-5 years. Extended loss of consciousness with baseline return and extended loss of consciousness without baseline return were independently associated with increased risk of developing hydrocephalus. Respiratory complication (OR, 28.35; 95% CI, 15.75-51.05; P < 0.0001), hemorrhage (OR, 37.12; 95% CI, 4.79-287.58; P = 0.0001), thromboembolic (OR, 8.57; 95% CI, 1.31-56.19; P = 0.025), and neurologic complication (OR, 64.64; 95% CI, 1.39-3010.2; P = 0.033) were all independently associated with increased risk of developing hydrocephalus.

Conclusions: Our study using the Nationwide Emergency Department Sample database shows that various demographic, hospital, and clinical risk factors are associated with the development of hydrocephalus after traumatic brain injury.
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http://dx.doi.org/10.1016/j.wneu.2020.04.216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484270PMC
September 2020

Influence of gender on discharge disposition after spinal fusion for adult spine deformity correction.

Clin Neurol Neurosurg 2020 07 1;194:105875. Epub 2020 May 1.

Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.

Objectives: Gender has been shown to impact several aspects of spine surgical care. However, the influence of gender disparities on discharge disposition after adult spine deformity correction (ASD) is relatively understudied. The aim of this study was to investigate the influence of gender on discharge disposition after elective spinal fusion involving ≥4 levels for ASD correction.

Patients And Methods: The Nationwide Inpatient Sample database (2011-2014) was queried for patients with ASD (≥26 years-old) and elective spine fusion surgery involving ≥4 levels using ICD-9 codes. Patients were stratified by gender: Male or Female. Multivariate linear and logistic regressions were used to assess the impact of gender on length of hospital stay and discharge disposition.

Results: A total of 4972 patients were identified of which 3282 (66.0%) were Female and 1690 (34.0%) were Male. The Male cohort had a higher prevalence of comorbidities than the Female cohort. There was a difference in the number of levels operated on between cohorts, with the Female cohort having fewer 4-8-level fusions (77.6% vs. 86.8%) and more 9+-level fusions (23.0% vs. 13.6%) compared to Males. The Female cohort had greater rates of postoperative UTI (5.5% vs. 2.5%) and surgical site hematomas (2.6% vs. 1.3%), while the Male cohort had more postoperative MI (5.4% vs. 1.5%). The Female cohort spent slightly more time in the hospital than Male cohort (6.2 days vs. 5.9 days, P = 0.035). Female patients had a significantly greater proportion of non-routine discharge disposition (F: 48.5% vs. M: 40.3%, P < 0.001) compared to Male patients. However, in a multivariate analysis including patient and hospital factors, gender was not an independent predictor of discharge disposition (OR: 0.976, CI: 0.865-1.101, P = 0.688), but was independently associated with increased LOS [female (RR: 0.331, CI: 0.106-0.556, P = 0.004)].

Conclusion: Our study suggests gender disparities may not have a significant impact on discharge disposition after spinal fusion for ASD involving four levels or greater. Further studies are necessary to understand risk factors for non-routine discharges in ASD patients to improve quality of patient care and reduced healthcare costs.
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http://dx.doi.org/10.1016/j.clineuro.2020.105875DOI Listing
July 2020

Thirty- and 90-Day Readmissions After Treatment of Traumatic Subdural Hematoma: National Trend Analysis.

World Neurosurg 2020 07 6;139:e212-e219. Epub 2020 Apr 6.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Radiology & Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Objective: Subdural hematoma (SDH), a form of traumatic brain injury, is a common disease that requires extensive patient management and resource utilization; however, there remains a paucity of national studies examining the likelihood of readmission in this patient population. The aim of this study is to investigate differences in 30- and 90-day readmissions for treatment of traumatic SDH using a nationwide readmission database.

Methods: The Nationwide Readmission Database years 2013-2015 were queried. Patients with a diagnosis of traumatic SDH and a primary procedure code for incision of cerebral meninges for drainage were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Patients were grouped by no readmission (Non-R), readmission within 30 days (30-R), and readmission within 31-90 days (90-R).

Results: We identified a total of 14,355 patients, with 3106 (21.6%) patients encountering a readmission (30-R: n = 2193 [15.3%]; 90-R: n = 913 [6.3%]; Non-R: n = 11,249). The most prevalent 30- and 90-day diagnoses seen among the readmitted cohorts were postoperative infection (30-R: 10.5%, 90-R: 13.0%) and epilepsy (30-R: 3.7%, 90-R: 1.1%). On multivariate logistic regression analysis, Medicare, Medicaid, hypertension, diabetes, renal failure, congestive heart failure, and coagulopathy were independently associated with 30-day readmission; Medicare and rheumatoid arthritis/collagen vascular disease were independently associated with 90-day readmission.

Conclusions: In this study, we determine the relationship between readmission rates and complications associated with surgical intervention for traumatic subdural hematoma.
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http://dx.doi.org/10.1016/j.wneu.2020.03.168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380544PMC
July 2020

Risk Factors Portending Extended Length of Stay After Suboccipital Decompression for Adult Chiari I Malformation.

World Neurosurg 2020 06 5;138:e515-e522. Epub 2020 Mar 5.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut. Electronic address:

Objective: For adult patients undergoing surgical decompression for Chiari malformation type I (CM-I), the patient-level factors that influence extended length of stay (LOS) are relatively unknown. The aim of this study was to investigate the impact of patient-baseline comorbidities, demographics, and postoperative complications on extended LOS after intervention after adult CM-I decompression surgery.

Methods: A retrospective cohort study using the National Inpatient Sample years 2010-2014 was performed. Adults (≥18 years) with a primary diagnosis of CM-I undergoing surgical decompression were identified. Weighted patient demographics, comorbidities, complications, LOS, disposition, and total cost were recorded. A multivariate logistic regression was used to determine the odds ratio for risk-adjusted LOS.

Results: A total of 29,961 patients were identified, 6802 of whom (22.7%) had extended LOS. The extended LOS cohort had a significantly greater overall complication rate (normal LOS, 10.6% vs. extended LOS, 29.1%; P < 0.001) and total cost (normal LOS, $14,959 ± $6037 vs. extended LOS, $25,324 ± $21,629; P < 0.001) compared with the normal LOS cohort. On multivariate logistic regression, black race, income quartiles, private insurance, obstructive hydrocephalus, lack of coordination, fluid and electrolyte disorders, and paralysis were all independently associated with extended LOS. Additional duraplasty (P = 0.132) was not significantly associated with extended LOS after adjusting for other variables. The odds ratio for extended LOS was 2.07 (95% confidence interval, 1.59-2.71) for patients with 1 complication and 9.47 (95% confidence interval, 5.86-15.30) for patients with >1 complication.

Conclusions: Our study shows that extended LOS after adult CM-I decompression surgery may be influenced by multiple patient-level factors.
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http://dx.doi.org/10.1016/j.wneu.2020.02.158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379177PMC
June 2020

MRI-Guided Laser Interstitial Thermal Therapy for Radiation Necrosis in Previously Irradiated Brain Arteriovenous Malformations.

Pract Radiat Oncol 2020 Jul - Aug;10(4):e298-e303. Epub 2020 Feb 14.

Departments of Neurosurgery, Yale School of Medicine, New Haven, Connecticut; Departments of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1016/j.prro.2020.02.003DOI Listing
March 2021

Laser Interstitial Thermotherapy for Treatment of Symptomatic Peritumoral Edema After Radiosurgery for Meningioma.

World Neurosurg 2020 Apr 27;136:295-300. Epub 2020 Jan 27.

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address:

Background: Symptomatic peritumoral edema (PTE) is a known complication after radiosurgical treatment of meningiomas. Although the edema in most patients can be successfully managed conservatively with corticosteroid therapy or bevacizumab, some medically refractory cases may require surgical resection of the underlying lesion when feasible. Laser interstitial thermotherapy (LITT) continues to gain traction as an effective therapeutic modality for the treatment of radiation necrosis where its biggest impact is through the control of peritumoral edema.

Case Description: A 56-year-old woman with neurofibromatosis 2 presented with a symptomatic, regrowing left frontotemporal lesion that had previously been radiated, then resected with confirmed recurrence of grade I meningioma, and subsequently radiated again for lesion recurrence. Given her history of 2 prior same-side craniotomies, including a complication of wound infection, she was not a candidate for further open surgical resection. Having failed conservative management, she underwent LITT with intraoperative biopsy demonstrating viable grade I meningioma. Postoperatively, she demonstrated radiographic marked, serial reduction of PTE and experienced resolution of her symptoms.

Conclusions: This case demonstrates that LITT may be a viable alternative treatment for patients with meningioma with symptomatic PTE who have failed medical therapy and require surgical intervention.
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http://dx.doi.org/10.1016/j.wneu.2020.01.143DOI Listing
April 2020

Independent Association Between Type of Intraoperative Blood Transfusion and Postoperative Delirium After Complex Spinal Fusion for Adult Deformity Correction.

Spine (Phila Pa 1976) 2020 Feb;45(4):268-274

Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina.

Study Design: Retrospective cohort study.

Objective: To determine whether type of intraoperative blood transfusion used is associated with increased incidence of postoperative delirium after complex spine fusion involving five levels or greater.

Summary Of Background Data: Postoperative delirium after spine surgery has been associated with age, cognitive status, and several comorbidities. Intraoperative allogenic blood transfusions have previously been linked to greater complication risks and length of hospital stay. However, whether type of intraoperative blood transfusion used increases the risk for postoperative delirium after complex spinal fusion remains relatively unknown.

Methods: The medical records of 130 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (more than or equal to five levels) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. We identified 104 patients who encountered an intraoperative blood transfusion. Of the 104, 15 (11.5%) had Allogenic-only, 23 (17.7%) had Autologous-only, and 66 (50.8%) had Combined transfusions. The primary outcome investigated was the rate of postoperative delirium.

Results: There were significant differences in estimated blood loss (Combined: 2155.5 ± 1900.7 mL vs. Autologous: 1396.5 ± 790.0 mL vs. Allogenic: 1071.3 ± 577.8 mL vs. None: 506.9 ± 427.3 mL, P < 0.0001) and amount transfused (Combined: 1739.7 ± 1127.6 mL vs. Autologous: 465.7 ± 289.7 mL vs. Allogenic: 986.9 ± 512.9 mL, P < 0.0001). The Allogenic cohort had a significantly higher proportion of patients experiencing delirium (Combined: 7.6% vs. Autologous: 17.4% vs. Allogenic: 46.7% vs. None: 11.5%, P = 0.002). In multivariate nominal-logistic regression analysis, Allogenic (odds ratio [OR]: 24.81, 95% confidence interval [CI] [3.930, 156.702], P = 0.0002) and Autologous (OR: 6.43, 95% CI [1.156, 35.772], P = 0.0335) transfusions were independently associated with postoperative delirium.

Conclusion: Our study suggests that there may be an independent association between intraoperative autologous and allogenic blood transfusions and postoperative delirium after complex spinal fusion. Further studies are necessary to identify the physiological effect of blood transfusions to better overall patient care and reduce healthcare expenditures.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003260DOI Listing
February 2020

Glymphatic System Impairment in Alzheimer's Disease and Idiopathic Normal Pressure Hydrocephalus.

Trends Mol Med 2020 03 18;26(3):285-295. Epub 2020 Jan 18.

Departments of Neurosurgery, Pediatrics, and Cellular and Molecular Physiology; and Yale-Rockefeller National Institutes of Health (NIH) Centers for Mendelian Genomics, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address:

Approximately 10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer's disease (AD) both exhibit sleep disturbances, build-up of brain metabolic wastes and amyloid-β (Aβ) plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte aquaporin-4 (AQP4). The glia-lymphatic (glymphatic) system facilitates brain fluid clearance and waste removal during sleep via glia-supported perivascular channels. Human studies have implicated impaired glymphatic function in both AD and iNPH. Continued investigation into the role of glymphatic system biology in AD and iNPH models could lead to new strategies to improve brain health by restoring homeostatic brain metabolism and CSF dynamics.
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http://dx.doi.org/10.1016/j.molmed.2019.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489754PMC
March 2020

Novel EWSR1-VGLL1 fusion in a pediatric neuroepithelial neoplasm.

Clin Genet 2020 05 16;97(5):791-792. Epub 2020 Jan 16.

Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1111/cge.13703DOI Listing
May 2020
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