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Congenital hydrocephalus (CH), characterized by incomplete clearance of CSF and subsequent enlargement of brain ventricles, is the most common congenital brain disorder. The lack of curative strategies for CH reflects a poor understanding of the underlying pathogenesis. Herein, the authors present an overview of recent findings in the pathogenesis of CH from human genetic studies and discuss the implications of these findings for treatment of CH. Findings from these omics data have the potential to reclassify CH according to a molecular nomenclature that may increase precision for genetic counseling, outcome prognostication, and treatment stratification. Beyond the immediate patient benefits, genomic data may also inform future clinical trials and catalyze the development of nonsurgical, molecularly targeted therapies. Therefore, the authors advocate for further application of genomic sequencing in clinical practice by the neurosurgical community as a diagnostic adjunct in the evaluation and management of patients diagnosed with CH.

This study aimed to investigate the impact of race on hospital length of stay (LOS) and hospital complications among pediatric patients with cervical/thoracic injury.A retrospective cohort was performed using the 2017 admission year from 753 facilities utilizing the National Trauma Data Bank. All pediatric patients with cervical/thoracic spine injuries were identified using the ICD-10-CM diagnosis coding system. These patients were segregated by their race, non-Hispanic white (NHW), non-Hispanic black (NHB), non-Hispanic Asian (NHA), and Hispanic (H). Demographic, hospital variable, hospital complications, and LOS data were collected. A linear and logistic multivariate regression analysis was performed to determine the risk ratio for hospital LOS as well as complication rate, respectively.A total of 4,125 pediatric patients were identified. NHB cohort had a greater prevalence of cervical-only injuries (NHW: 37.39% vs. NHB: 49.93% vs. NHA: 34.29% vs. H: 38.71%, P0.001). While transport accident was most common injury etiology for both cohorts, NHB cohort had a greater prevalence of assault (NHW: 1.53% vs. NHB: 17.40% vs. NHA: 2.86% vs. H: 6.58%, P0.001) than the other cohorts. Overall complication rates were significantly higher among NHB patients (NHW: 9.39% vs. NHB: 15.12% vs. NHA: 14.29% vs. H: 13.60%, P0.001). Compared with the NHW cohort, NHB, NHA, and H had significantly longer hospital LOS (NHW: 6.15 ± 9.03 days vs. NHB: 9.24 ± 20.78 days vs. NHA: 9.09 ± 13.28 days vs. H: 8.05 ± 11.45 days, P0.001). NHB race was identified as a significant predictor of increased LOS on multivariate regression analysis (risk ratio: 1.14, 95% confidence interval: 0.46, 1.82; P = 0.001) but not hospital complications (P = 0.345).Race may significantly impact health care resource utilization following pediatric cervical/thoracic spinal trauma.

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).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.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; P0.001), 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; P0.001) but not postoperative complication or 30-day unplanned readmission.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.

Introduction Spontaneous cerebrospinal fluid (CSF) leaks represent a unique clinical presentation of idiopathic intracranial hypertension (IIH), lacking classical features of IIH, including severe headaches, papilledema, and markedly elevated opening pressures. Methods Following a single-institution retrospective review of patients undergoing spontaneous CSF leak repair, we performed a literature review of spontaneous CSF leak in patients previously undiagnosed with IIH, querying PubMed. Results Our literature review yielded 26 studies, comprising 716 patients. Average age was 51 years with 80.8% female predominance, and average body mass index was 35.5. Presenting symptoms included headaches (32.5%), visual disturbances (4.2%), and a history of meningitis (15.3%). Papilledema occurred in 14.1%. An empty sella was present in 77.7%. Slit ventricles and venous sinus stenosis comprised 7.7 and 31.8%, respectively. CSF leak most commonly originated from the sphenoid sinus (41.1%), cribriform plate (25.4%), and ethmoid skull base (20.4%). Preoperative opening pressures were normal at 22.4 cm H2O and elevated postoperatively to 30.8 cm H2O. 19.1% of patients underwent shunt placement. CSF leak recurred after repair in 10.5% of patients, 78.6% involving the initial site. A total of 85.7% of these patients were managed with repeat surgical intervention, and 23.2% underwent a shunting procedure. Conclusion Spontaneous CSF leaks represent a distinct variant of IIH, distinguished by decreased prevalence of headaches, lack of visual deficits, and normal opening pressures. Delayed measurement of opening pressure after leak repair may be helpful to diagnose IIH. Permanent CSF diversion may be indicated in patients exhibiting significantly elevated opening pressures postoperatively, refractory symptoms of IIH, or recurrent CSF leak.

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.

Fetal intracranial haemorrhage (ICH) is a pathophysiological process involving haemorrhagic and hypoxic–ischaemic insults resulting in antenatal brain damage. Insults to the central nervous system are usually not detected until the second or third trimester. In this case presentation, we present a possible prenatal ultrasound marker, ‘worm sign’, representing cortical disruption secondary to suspected ICH at 13 weeks’ gestation. According to current literature review, this is one of the first cases of ICH, diagnosed in the first‐trimester and highlights the importance of early neurovascular and structural evaluation of the fetal brain at the time of first‐trimester ultrasound screening.

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 (

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.

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.

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.

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. 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. 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. 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.

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 STAG2 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 EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, 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 STAG2 deficiency. As such, this case represents a novel report following the clinical and genetic progression of a STAG2 mutated glioblastoma, including treatment with a novel and emerging immunotherapy. Although STAG2 deficiency comprises only a small subset of gliomas, this case adds clinical evidence to existing preclinical data supporting a role for STAG2 mutations in gliomagenesis and resistance to standard therapies.

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.

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.

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

Pediatric midline tumors are devastating high-grade lesions with a dismal prognosis and no curative surgical options. Here, the authors report the clinical presentation, surgical management, whole-exome sequencing (WES), and clonality analysis of a patient with a radically resected H3K27M-mutant pineal parenchymal tumor (PPT) and spine metastases consistent with PPT of intermediate differentiation (PPTID). They identified somatic mutations in H3F3A (H3K27M), FGFR1, and NF1 both in the original PPT and in the PPTID metastases. They also found 12q amplification containing CDK4/MDM2 and chromosome 17 loss of heterozygosity overlapping with NF1 that resulted in biallelic NF1 loss. They noted a hypermutated phenotype with increased C>T transitions within the PPTID metastases and 2p amplification overlapping with the MYCN locus. Clonality analysis detected three founder clones maintained during progression and metastasis. Tumor clones present within the PPTID metastases but not the pineal midline tumor harbored mutations in APC and TIMP2.While the majority of H3K27M mutations are found in pediatric midline gliomas, it is increasingly recognized that this mutation is present in a wider range of lesions with a varied morphological appearance. The present case appears to be the first description of H3K27M mutation in PPTID. Somatic mutations in H3F3A, FGFR1, and NF1 have been suggested to be driver mutations in pediatric midline gliomas. Their clonality and presence in over 80% of tumor cells in our patient’s PPTID are consistent with similarly crucial roles in early tumorigenesis, with progression mediated by copy number variations and chromosomal aberrations involving known oncogenes and tumor suppressors. The roles of APC and TIMP2 mutations in progression and metastasis remain to be investigated.

OBJECTIVEIn the past decade, a gradual transition of health policy to value-based healthcare has brought increased attention to measuring the quality of care delivered. In spine surgery, adolescents with scoliosis are a population particularly at risk for depression, anxious feelings, and impaired quality of life related to back pain and cosmetic appearance of the deformity. With the rising prevalence of mental health ailments, it is necessary to evaluate the impact of concurrent affective disorders on patient care after spinal surgery in adolescents. The aim of this study was to investigate the impact that affective disorders have on perioperative complication rates, length of stay (LOS), and total costs in adolescents undergoing elective posterior spinal fusion (PSF) (≥ 4 levels) for idiopathic scoliosis.METHODSA retrospective study of the Kids’ Inpatient Database for the year 2012 was performed. Adolescent patients (age range 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 categorized into 2 groups at discharge: affective disorder or no affective disorder. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were assessed. The primary outcomes were perioperative complication rates, LOS, total cost, and discharge dispositions.RESULTSThere were 3759 adolescents included in this study, of whom 164 (4.4%) were identified with an affective disorder (no affective disorder: n = 3595). Adolescents with affective disorders were significantly older than adolescents with no affective disorders (affective disorder: 14.4 ± 1.9 years vs no affective disorder: 13.9 ± 1.8 years, p = 0.001), and had significantly different proportions of race (p = 0.005). Aside from hospital region (p = 0.016), no other patient- or hospital-level factors differed between the cohorts. Patient comorbidities did not differ significantly between cohorts. The number of vertebral levels involved was similar between the cohorts, with the majority of patients having 9 or more levels involved (affective disorder: 76.8% vs no affective disorder: 79.5%, p = 0.403). Postoperative complications were similar between the cohorts, with no significant difference in the proportion of patients experiencing a postoperative complication (p = 0.079) or number of complications (p = 0.124). The mean length of stay and mean total cost were similar between the cohorts. Moreover, the routine and nonroutine discharge dispositions were also similar between the cohorts, with the majority of patients having routine discharges (affective disorder: 93.9% vs no affective disorder: 94.9%, p = 0.591).CONCLUSIONSThis study suggests that affective disorders may not have a significant impact on surgical outcomes in adolescent patients undergoing surgery for scoliosis in comparison with adults. Further studies are necessary to elucidate how affective disorders affect adolescent patients with idiopathic scoliosis, which may improve provider approach in managing these patients perioperatively and at follow-up in hopes to better the overall patient satisfaction and quality of care delivered.

OBJECTIVEHealth policy changes have led to increased emphasis on value-based care to improve resource utilization and reduce inpatient hospital length of stay (LOS). Recently, LOS has become a major determinant of quality of care and resource utilization. For adolescent idiopathic scoliosis (AIS), the determinants of extended LOS after elective posterior spinal fusion (PSF) remain relatively unknown. In the present study, the authors investigated the impact of patient and hospital-level risk factors on extended LOS following elective PSF surgery (≥ 4 levels) for AIS.METHODSThe Kids’ Inpatient Database (KID) was queried for the year 2012. Adolescent patients (age range 10–17 years) with AIS undergoing elective PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended hospital LOS was defined as greater than the 75th percentile for the entire cohort (> 6 days), and patients were dichotomized as having normal LOS or extended LOS. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were recorded. A multivariate logistic regression model 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.RESULTSComorbidities were overall significantly higher in the extended-LOS cohort than the normal-LOS cohort. Patients with extended LOS had a significantly greater proportion of blood transfusion (p < 0.001) and ≥ 9 vertebral levels fused (p < 0.001). The overall complication rates were greater in the extended-LOS cohort (20.3% [normal-LOS group] vs 43.5% [extended-LOS group]; p < 0.001). On average, the extended-LOS cohort incurred $18,916 more in total cost than the normal-LOS group ($54,697 ± $24,217 vs $73,613 ± $38,689, respectively; p < 0.001) and had more patients discharged to locations other than home (p < 0.001) than did patients in the normal-LOS cohort. On multivariate logistic regression, several risk factors were associated with extended LOS, including female sex, obesity, hypertension, fluid electrolyte disorder, paralysis, blood transfusion, ≥ 9 vertebrae fused, dural injury, and nerve cord injury. The odds ratio for extended LOS was 1.95 (95% CI 1.50–2.52) for patients with 1 complication and 5.43 (95% CI 3.35–8.71) for patients with > 1 complication.CONCLUSIONSThe authors’ study using the KID demonstrates that patient comorbidities and intra- and postoperative complications all contribute to extended LOS after spinal fusion for AIS. Identifying multimodality interventions focused on reducing LOS, bettering patient outcomes, and lowering healthcare costs are necessary to improve the overall value of care for patients undergoing spinal fusion for AIS.

Objective Previous studies have identified the impact of affective disorders on preoperative and postoperative perception of pain. However, there is a scarcity of data identifying the impact of affective disorders on postdischarge narcotic refills. The aim of this study was to determine whether patients with affective disorders have more narcotic refills after complex spinal fusion for deformity correction. Methods The medical records of 121 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (≥5 level) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. Patient demographics, comorbidities, intraoperative and postoperative complication rates, baseline and postoperative patient-reported pain scores, ambulatory status, and narcotic refills were collected for each patient. The primary outcome was the rate of 6-week and 3-month narcotic refills. Results Of the 121 patients, 43 (35.5%) had a clinical diagnosis of anxiety or depression (affective disorder) (AD n = 43; No-AD n = 78). Preoperative narcotic use was significantly higher in the AD cohort (AD 65.9% vs. No-AD 37.7%, P = 0.0035). The AD cohort had significantly higher pain scores at baseline (AD 6.5 ± 2.9 vs. No-AD 4.7 ± 3.1, P = 0.004) and at the first postoperative pain score reported (AD 6.7 ± 2.6 vs. No-AD 5.6 ± 2.9, P = 0.049). However, there were no significant differences in narcotic refills at 6 weeks (AD 34.9% vs. No-AD 25.6%, P = 0.283) and 3 months (AD 23.8% vs. No-AD 17.4%, P = 0.411) after discharge between the cohorts. Conclusions Our study suggests that whereas spinal deformity patients with affective disorders may have a higher baseline perception of pain and narcotic use, the impact of affective disorders on narcotic refills at 6 weeks and 3 months may be minimal after complex spinal fusion.

Background: For complex surgery, intraoperative ketamine administration is readily used to reduce post-operative pain. However, there have been a few studies suggesting that intraoperative ketamine may have deleterious effects and impact post-operative delirium. Therefore, we sought to identify the impact that intraoperative ketamine has on post-operative outcomes after complex spinal surgery involving ≥5 level fusions. Methods: The medical records of 138 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (≥5 level) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. We identified 98 (71.0%) who had intraoperative ketamine administration and 40 (29%) who did not (Ketamine-Use: n=98; No-Ketamine: n=40). Patient demographics, comorbidities, intra- and post-operative complication rates were collected for each patient. The primary outcome investigated in this study was the rate of post-operative delirium. A multivariate nominal-logistic regression analysis was used to determine the independent association between intraoperative ketamine and post-operative delirium. Results: Patient demographics and comorbidities were similar between both cohorts, including age, gender, and BMI. The median number of fusion levels operated, length of surgery, estimated blood loss, and proportion of patients requiring blood transfusions were similar between both cohorts. Postoperative complication profile was similar between the cohorts, except for the Ketamine-Use cohort having significantly higher proportion of patients experiencing delirium (Ketamine-Use: 14.3% vs . No-Ketamine: 2.6%, P=0.047). In a multivariate nominal-logistic regression analysis, intraoperative Ketamine-Use was independently associated with post-operative delirium (OR: 9.475, 95% CI: 1.026–87.508, P=0.047). Conclusions: Our study suggests that the intraoperative use of ketamine may increase the risk of post-operative delirium. Further studies are necessary to understand the physiological effect intraoperative ketamine has on patients undergoing complex spinal fusions in order to better overall patient care and reduce healthcare resources.

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.

The lack of effective treatments for autism spectrum disorder (ASD) and congenital hydrocephalus (CH) reflects the limited understanding of the biology underlying these common neurodevelopmental disorders. Although ASD and CH have been extensively studied as independent entities, recent human genomic and pre-clinical animal studies have uncovered shared molecular pathophysiology. Here, we review and discuss phenotypic, genomic, and molecular similarities between ASD and CH, and identify the PTEN-PI3K-mTOR (phosphatase and tensin homolog-phosphoinositide 3-kinase-mammalian target of rapamycin) pathway as a common underlying mechanism that holds diagnostic, prognostic, and therapeutic promise for individuals with ASD and CH.

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.

Absence seizures are characterized by a brief behavioural impairment including apparent loss of consciousness. Neuronal mechanisms determining the behavioural impairment of absence seizures remain unknown, and their elucidation might highlight therapeutic options for reducing seizure severity. However, recent studies have questioned the similarity of animal spike-wave-discharges (SWD) to human absence seizures both behaviourally and neuronally. Here, we report that Genetic Absence Epilepsy Rats from Strasbourg recapitulate the decreased neuroimaging signals and loss of consciousness characteristic of human absence seizures. Overall neuronal firing is decreased but rhythmic in the somatosensory cortex and thalamus during these seizures. Interestingly, individual neurons in both regions tend to consistently express one of four distinct patterns of seizure-associated activity. These patterns differ in firing rate dynamics and in rhythmicity during seizure. One group of neurons showed a transient initial peak in firing at SWD onset, accounting for the brief initial increase in overall neuronal firing seen in cortex and thalamus. The largest group of neurons in both cortex and thalamus showed sustained decreases in firing during SWD. Other neurons showed either sustained increases or no change in firing. These findings suggest that certain classes of cortical and thalamic neurons may be particularly responsible for the paroxysmal oscillations and consequent loss of consciousness in absence epilepsy.

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.

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.

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 similar 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.

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 PTCH1 and BCOR 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 PTCH1 and BCOR mutations, into the pathophysiology of sellar metastasis from primary systemic tumors.

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 de novo 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.

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 (P < .001), anatomical location (P < .001), extent of resection (P < .001), radiation use (P < .001), tumor grade (P < .001), histological classification (P < .001), and all-cause mortality (P < .001). There was no significant difference between cohorts with respect to gender (P = .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.

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. SIGNIFICANCE STATEMENT 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.

Background/Aims: Interventional MRI (iMRI) allows real-time confirmation of electrode and microcatheter location in anesthetized patients; however, MRI-compatible pneumatic compression devices (PCD) to reduce the periprocedural venous thromboembolism (VTE) risk are not commercially available. Given the paucity of literature on VTE following iMRI surgery, better characterizing patients suffering this complication and the incidence of this event following iMRI procedures is pivotal for defining best surgical practices. We aim to investigate the incidence of postoperative VTE in iMRI procedures without the use of PCD. Methods: Medical records and operative times of patients were retrospectively reviewed. Patient demographics and mean surgical durations were reported with statistical comparisons via ANOVA and the 2-tailed Student t test, an α of 0.05, and the Bonferroni correction. Patients experiencing postoperative VTE underwent an in-depth chart review. Results: Two out of two hundred ten (0.95%) iMRI procedures resulted in postoperative VTE events. There were statistically significant differences in procedure times between unilateral electrode (157.5 ± 5.7 min), bilateral electrode (193.6 ± 2.9 min), and bilateral gene therapy procedures (467.3 ± 26.5 min). Both patients had longer-than-average operative times for their respective procedures. Conclusions: The incidence of postoperative VTE is low following iMRI procedures, even without the use of PCD during surgery.

Radiation necrosis (RN) is a well described complication seen after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVM). First-line medical therapies are not always successful in alleviating symptoms and management of some cases may require open surgical resection of the lesion. Surgery is often thought of however as a last resort given its associated morbidity especially in the setting of potential concern for residual live AVM. Magnetic resonance imaging (MRI)-guided laser interstitial thermotherapy (LITT) is a minimally invasive surgical procedure that is being increasingly considered for RN lesions and is best established for treatment of symptomatic RN that can develop after stereotactic radiosurgical treatment of metastatic brain tumors. Its ability to treat RN from other primary pathologies remains unclear. Here, we present 2 cases that show successful use of LITT in patients with biopsy-confirmed RN post-radiosurgery for AVMs. As with tumor-associated RN, LITT can result in rapid improvement of symptoms related to reduction in perilesional edema and then shrinkage and eventual stabilization of the RN lesion.

The aim of this study was to evaluate regional variations in the management, complications, and total cost of admission for adolescent idiopathic scoliosis (AIS) treated by elective posterior spinal surgery (PSF, ≥4 levels).The Kids' Inpatient Database year 2012 was queried and adolescent patients (age 10-17 years old) with AIS undergoing elective PSF (≥4 levels) were selected. The primary outcome was regional variations for intraoperative and postoperative complications, length of surgery, and total cost of admission after elective PSF intervention.In our cohort of 3759 adolescent patients identified, 704 (18.7%) patients were treated in the Northeast, 917 (24.4%) in the Midwest, 1329 (35.4%) in the South, and 809 (21.5%) in the West (Northeast: n = 704; Midwest: n = 917; South: n = 1329; West: n = 809). The Northeast had the greatest complication rate, followed by the Midwest, South, and West region cohorts (Northeast: 27.7% vs. Midwest: 24.5% vs. South: 23.0% vs. West: 17.2%, P 0.001). On average, length of surgery was shortest in the South (Northeast: 5.3 ± 2.7 days vs. Midwest: 5.3 ± 3.1 days vs. South: 4.9 ± 3.1 days vs. West: 5.3 ± 2.1 days, P 0.001), while the total cost of admission was greatest in the West (Northeast: $51,760 ± $25,177 vs. Midwest: $55,201 ± $23,750 vs. South: $58,847 ± $28,227 vs. West: $60,636 ± $29,372, P0.001).Our study suggests that there may be regional variations in health care resource utilization in AIS patients undergoing multilevel posterior spinal fusions. Further study is warranted to determine the specific factors contributing to disparities in regional outcomes.

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.

A 10-year-old girl presented with excessive sweating overlying her right scapula (figure) and stable right leg weakness due to an underlying solid cystic pilocytic astrocytoma spanning T3–T12, debulked 5 months earlier, subsequently re-decompressed with syringosubarachnoid shunt placement secondary to intrasyrinx hemorrhage. MRI demonstrated mild tumor and syrinx progression at T5–T8, limited to the right side (figure, B–E). Focal segmental hyperhidrosis is rare, previously reported in Chiari and trauma-related syringomyelia.1,2 Here, unilateral hyperhidrosis was caused by ipsilateral tumor and syrinx progression. The pathophysiology may be from local tissue damage causing hyperactivity of preganglionic sympathetic neurons or disinhibition of inhibitory local interneurons.2

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).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.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).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.

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).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.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 (p0.001). 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, p0.001) 11-15 years (OR: 0.41, p0.001), and 16-20 years (OR: 0.51, p0.001) were independently associated with decreased risk of developing seizures. Extended LOC with baseline return (OR: 6.33, p0.001), extended LOC without baseline return (OR: 1.95, p = 0.009), and Other LOC (OR: 3.02, p0.001) were independently associated with increased risk of developing seizures. Subarachnoid hemorrhage (OR: 4.14, p0.001), subdural hemorrhage [OR: 7.72, p0.001), and extradural hemorrhage (OR: 3.13, p0.001) were all independently associated with increased risk of developing seizures.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.

Impaired breathing, cardiac function, and arousal during and after seizures are important causes of morbidity and mortality. Previous work suggests that these changes are associated with depressed brainstem function in the ictal and post-ictal periods. Lower brainstem serotonergic systems are postulated to play an important role in cardiorespiratory changes during and after seizures, whereas upper brainstem serotonergic and other systems regulate arousal. However, direct demonstration of seizure-associated neuronal activity changes in brainstem serotonergic regions has been lacking. Here, we performed multiunit and single-unit recordings from medullary raphe and midbrain dorsal raphe nuclei in an established rat seizure model while measuring changes in breathing rate and depth as well as heart rate. Serotonergic neurons were identified by immunohistochemistry. Respiratory rate, tidal volume, and minute ventilation were all significantly decreased during and after seizures in this model. We found that population firing of neurons in the medullary and midbrain raphe on multiunit recordings was significantly decreased during the ictal and post-ictal periods. Single-unit recordings from identified serotonergic neurons in the medullary raphe revealed highly consistently decreased firing during and after seizures. In contrast, firing of midbrain raphe serotonergic neurons was more variable, with a mixture of increases and decreases. The markedly suppressed firing of medullary serotonergic neurons supports their possible role in simultaneously impaired cardiorespiratory function in seizures. Decreased arousal likely arises from depressed population activity of several neuronal pools in the upper brainstem and forebrain. These findings have important implications for preventing morbidity and mortality in people living with epilepsy.SIGNIFICANCE STATEMENTSeizures often cause impaired breathing, cardiac dysfunction, and loss of consciousness. The brainstem and, specifically, brainstem serotonin neurons are thought to play an important role in controlling breathing, cardiac function, and arousal. We used an established rat seizure model to study the overall neuronal activity in the brainstem as well as firing of specific serotonin neurons while measuring cardiorespiratory function. Our results demonstrated overall decreases in brainstem neuronal activity and marked downregulation of lower brainstem serotonin neuronal firing in association with decreased breathing and heart rate during and after seizures. These findings point the way toward new treatments to augment brainstem function and serotonin, aiming to prevent seizure complications and reduce morbidity and mortality in people living with epilepsy.

Summary 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 de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel γ-1 subunit (GABRG1) 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 Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis., Graphical Abstract, Highlights • Genomic analysis of trigeminal neuralgia (TN) using exome sequencing • Rare mutations in GABA signaling and ion transport genes are enriched in TN cases • Generation of a genetic TN mouse model engineered with a patient-specific mutation, Neuroscience; Structural Biology; Genomics

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.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).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 with1 complication.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.

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.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.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)].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.