Primary intraosseous xanthoma of the frontal bone in a child: illustrative case.

BACKGROUND: Skull lesions are a common finding in children, with dermoid cysts and eosinophilic granulomas observed most frequently. However, primary intraosseous xanthomas of the calvaria, which are lytic, expansile lesions that develop without underlying hyperlipidemic disease, are rare in children, with only one prior case reported. OBSERVATIONS: The authors describe the case of a healthy 6-year-old male who presented with a 2-month history of an enlarging midline skull mass that developed after a recent minor trauma. Imaging showed a full-thickness, lytic frontal bone lesion with an aggressive appearance and heterogeneous contrast enhancement. The patient underwent gross-total resection of the lesion with placement of a mesh cranioplasty. Histopathology revealed a primary intraosseous xanthoma. The patient was discharged on postoperative day 2 and required no further treatment at the 1-month follow-up. LESSONS: This is the first reported case of a primary intraosseous xanthoma in the frontal bone of a pediatric patient. It emphasizes the need to include primary xanthomas in the differential diagnosis for pediatric skull lesions, particularly when the lesion has an aggressive radiographic appearance or the patient has a history of focal trauma. Furthermore, our findings indicate that resection, together with subsequent monitoring for lesion reccurrence, is an adequate first-line treatment.

Multiomic analyses implicate a neurodevelopmental program in the pathogenesis of cerebral arachnoid cysts.

Cerebral arachnoid cysts (ACs) are one of the most common and poorly understood types of developmental brain lesion. To begin to elucidate AC pathogenesis, we performed an integrated analysis of 617 patient-parent (trio) exomes, 152,898 human brain and mouse meningeal single-cell RNA sequencing transcriptomes and natural language processing data of patient medical records. We found that damaging de novo variants (DNVs) were highly enriched in patients with ACs compared with healthy individuals (P = 1.57 × 10-33). Seven genes harbored an exome-wide significant DNV burden. AC-associated genes were enriched for chromatin modifiers and converged in midgestational transcription networks essential for neural and meningeal development. Unsupervised clustering of patient phenotypes identified four AC subtypes and clinical severity correlated with the presence of a damaging DNV. These data provide insights into the coordinated regulation of brain and meningeal development and implicate epigenomic dysregulation due to DNVs in AC pathogenesis. Our results provide a preliminary indication that, in the appropriate clinical context, ACs may be considered radiographic harbingers of neurodevelopmental pathology warranting genetic testing and neurobehavioral follow-up. These data highlight the utility of a systems-level, multiomics approach to elucidate sporadic structural brain disease.

Management of dynamic cervical kyphosis with dorsal epidural lipomatosis: a Hirayama disease variant? Illustrative case.

BACKGROUND: Hirayama disease, a cervical myelopathy characterized most commonly by a self-limiting atrophic weakness of the upper extremities, is a rare entity, scarcely reported in the literature. Diagnosis is made by spinal magnetic resonance imaging (MRI), which typically shows loss of normal cervical lordosis, anterior displacement of the cord during flexion, and a large epidural cervical fat pad. Treatment options include observation or cervical immobilization by collar or surgical decompression and fusion. OBSERVATIONS: Here, the authors report an unusual case of a Hirayama-like disease in a young White male athlete who presented with rapidly progressive paresthesia in all 4 extremities and no weakness. Imaging showed characteristic findings of Hirayama disease as well as worsened cervical kyphosis and spinal cord compression in cervical neck extension, which has not previously been reported. Two-level anterior cervical discectomy and fusion and posterior spinal fusion improved both cervical kyphosis on extension and symptoms. LESSONS: Given the disease's self-limiting nature, and a lack of current reporting, there remains no consensus on how to manage these patients. Such findings presented here demonstrate the potentially heterogeneous MRI findings that can be observed in Hirayama disease and emphasize the utility of aggressive surgical management in young, active patients whereby a cervical collar may not be tolerated.

Familial and syndromic forms of arachnoid cyst implicate genetic factors in disease pathogenesis.

Arachnoid cysts (ACs) are the most common space-occupying lesions in the human brain and present significant challenges for clinical management. While most cases of ACs are sporadic, nearly 40 familial forms have been reported. Moreover, ACs are seen with increased frequency in multiple Mendelian syndromes, including Chudley-McCullough syndrome, acrocallosal syndrome, and autosomal recessive primary ciliary dyskinesia. These findings suggest that genetic factors contribute to AC pathogenesis. However, traditional linkage and segregation approaches have been limited in their ability to identify causative genes for ACs because the disease is genetically heterogeneous and often presents asymptomatically and sporadically. Here, we comprehensively review theories of AC pathogenesis, the genetic evidence for AC formation, and discuss a different approach to AC genomics that could help elucidate this perplexing lesion and shed light on the associated neurodevelopmental phenotypes seen in a significant subset of these patients.

A neural stem cell paradigm of pediatric hydrocephalus.

Pediatric hydrocephalus, the leading reason for brain surgery in children, is characterized by enlargement of the cerebral ventricles classically attributed to cerebrospinal fluid (CSF) overaccumulation. Neurosurgical shunting to reduce CSF volume is the default treatment that intends to reinstate normal CSF homeostasis, yet neurodevelopmental disability often persists in hydrocephalic children despite optimal surgical management. Here, we discuss recent human genetic and animal model studies that are shifting the view of pediatric hydrocephalus from an impaired fluid plumbing model to a new paradigm of dysregulated neural stem cell (NSC) fate. NSCs are neuroprogenitor cells that comprise the germinal neuroepithelium lining the prenatal brain ventricles. We propose that heterogenous defects in the development of these cells converge to disrupt cerebrocortical morphogenesis, leading to abnormal brain-CSF biomechanical interactions that facilitate passive pooling of CSF and secondary ventricular distention. A significant subset of pediatric hydrocephalus may thus in fact be due to a developmental brain malformation leading to secondary enlargement of the ventricles rather than a primary defect of CSF circulation. If hydrocephalus is indeed a neuroradiographic presentation of an inborn brain defect, it suggests the need to focus on optimizing neurodevelopment, rather than CSF diversion, as the primary treatment strategy for these children.

Child Neurology: Functional Reorganization Mediating Supplementary Motor Area Syndrome Recovery in Agenesis of the Corpus Callosum.

Supplementary motor area (SMA) syndrome is a typically transient condition resulting from damage to the medial premotor cortex. The exact mechanism of recovery remains unknown but is traditionally described as a process involving functional compensation by the contralateral SMA through corpus callosal fibers. The purpose of this case study is to highlight a distinct extra-callosal mechanism of functional recovery from SMA syndrome in a patient with agenesis of the corpus callosum (ACC). We present the clinical presentation and perioperative functional neuroimaging features of a 16-year-old patient with complete ACC who exhibited recovery from an SMA syndrome resulting from surgical resection of a right-sided low-grade glioma. Preoperative functional MRI (fMRI) revealed anatomically concordant activation areas during finger and toe tapping tasks bilaterally. Three months following surgery, the patient had fully recovered, and a repeat fMRI revealed shift of the majority of the left toe tapping area from the expected contralateral hemisphere to the ipsilateral left paracentral lobule and SMA. The fMRI signal remodeling observed in this acallosal patient suggests that within-hemisphere plasticity of the healthy hemisphere may constitute an alternative critical process in SMA syndrome resolution and challenges the traditional view that transcallosal fibers are necessary for functional recovery.

A Unique Subset: Idiopathic Intracranial Hypertension Presenting as Spontaneous CSF Leak of the Anterior Skull Base.

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 H 2 O and elevated postoperatively to 30.8 cm H 2 O. 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.

Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus.

Hydrocephalus, characterized by cerebral ventricular dilatation, is routinely attributed to primary defects in cerebrospinal fluid (CSF) homeostasis. This fosters CSF shunting as the leading reason for brain surgery in children despite considerable disease heterogeneity. In this study, by integrating human brain transcriptomics with whole-exome sequencing of 483 patients with congenital hydrocephalus (CH), we found convergence of CH risk genes in embryonic neuroepithelial stem cells. Of all CH risk genes, TRIM71/lin-41 harbors the most de novo mutations and is most specifically expressed in neuroepithelial cells. Mice harboring neuroepithelial cell-specific Trim71 deletion or CH-specific Trim71 mutation exhibit prenatal hydrocephalus. CH mutations disrupt TRIM71 binding to its RNA targets, causing premature neuroepithelial cell differentiation and reduced neurogenesis. Cortical hypoplasia leads to a hypercompliant cortex and secondary ventricular enlargement without primary defects in CSF circulation. These data highlight the importance of precisely regulated neuroepithelial cell fate for normal brain-CSF biomechanics and support a clinically relevant neuroprogenitor-based paradigm of CH.

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

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.

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

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.

Hypermutated phenotype in gliosarcoma of the spinal cord.

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.

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

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.

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

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.

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

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.

Laser interstitial thermal therapy in neuro-oncology applications.

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.

Laser interstitial thermal therapy for treatment of cerebral radiation necrosis.

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.

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

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.

Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma.

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.

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

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.