Pediatric infectious aneurysms: individual patient pooled analysis on presentation, management and outcomes.

BACKGROUND: Infectious intracranial aneurysms (IIAs) are a rare sequel of systemic infection and occur most commonly in patients with infective endocarditis (IE). Despite the increasing use of non-invasive screening angiography in patients with IE, the incidence remains low, yielding limited data on the management of IIAs in pediatric populations. We performed a pooled analysis of all published series of pediatric patients with IIAs to study the disease landscape including presentation, management, and outcomes. METHODS: Data included in this study were pooled from published literature on IIAs between 1960 and 2023. Abstracts were selected for full review to include only manuscripts reporting at least one case of pediatric IIA (age 0-18 years). RESULTS: A total of 145 pediatric patients with 178 IIAs were included. Patients presented with rupture in 68% of cases, of which 36% had intraparenchymal hemorrhage and 39% had subarachnoid hemorrhage. Using multivariate logistic regression, independent predictors of rupture were posterior location (aOR 10, P=0.041) and history of IE (aOR 7.2, P=0.001). Primary medical management was successful in 82% of cases with unruptured aneurysms while, in those with ruptured IIAs, medical management was successful in 26% of cases. The 90-day mortality rate was 28%. Using multivariate logistic regression, ruptured IIAs (aOR 5.4, P<0.01) and failure of medical management (aOR 11.1, P<0.05) were independent predictors of 90-day mortality. CONCLUSION: Pediatric IIAs remain a rare complication of systemic or localized CNS infection in the pediatric population. Medical management of unruptured aneurysms is highly successful, while ruptured aneurysms have a remarkably high rate of failure of medical management and should be treated by early surgical or endovascular intervention when feasible.

Application of a Halo Fixator for the Treatment of Pediatric Spinal Deformity.

BACKGROUND: In spine surgery, the halo fixator was initially utilized to stabilize cervical fusions in patients with poliomyelitis. More recently, the indications for halo fixation have evolved to include stabilization and definitive treatment for upper cervical spine injuries (Jefferson fractures, atlanto-occipital dissociations, odontoid fractures, etc.), treatment of atlantoaxial rotatory subluxation, stabilization of long cervical fusions, and preoperative traction. In the realm of pediatric spinal deformity, halo fixation has proved to be a valuable resource for severe or neglected spinal deformities. In this video article, we demonstrate the application of a halo fixator in a pediatric patient with severe scoliosis. DESCRIPTION: The procedure includes appropriate pin placement in the safe zones of the skull performed under either general anesthesia or local anesthesia. Pins are secured to a halo frame that is sized to be 2 cm larger than the circumference of the skull and are tightened according to age-specific torque guidelines. ALTERNATIVES: Alternative treatments vary from cervical spine immobilization to definitive surgical treatment in the spine, or even spinal osteotomies, depending on the underlying spinal pathology. RATIONALE: The halo fixator works by limiting motion of the cervical spine in flexion, extension, and axial rotation. The halo is also able to control and correct translational injuries of the cervical spine. In the setting of spinal deformity, the halo fixator can also be utilized to overcome the effects of gravity and lengthen the spine. EXPECTED OUTCOMES: For spinal deformities, the halo fixator can be expected to lengthen the spine and increase deformity flexibility prior to definitive surgical treatment in the spine or growth-friendly spinal instrumentation. IMPORTANT TIPS: Correct identification of safe zones for pin placement is vital to correct pin placement.For pediatric patients, it is important to obtain fixation with a minimum of 6 to 8 pins.Pins should be tightened with use of a torque-limiting wrench, up to no more than 1 in/lb (55.9 mm/kg) per year of age, up to a maximum of 8 in/lb (447.9 mm/kg).Applied traction should be a maximum of 50% of the body weight of the patient.Neurovascular examination is vital following application of weight.

Utility of ventriculogallbladder shunts in complex cases of hydrocephalus related to extreme prematurity.

OBJECTIVE: The management of hydrocephalus resulting from intraventricular hemorrhage related to extreme prematurity remains demanding. Given the complexities of controlling hydrocephalus in this population, less commonly used procedures may be required. The authors examined the utility of ventriculogallbladder (VGB) shunts in a series of such children. METHODS: The authors retrospectively reviewed the medical records of all children who underwent surgery for hydrocephalus in the period from 2011 through 2019 at Children's Healthcare of Atlanta. Six patients who underwent VGB shunt placement were identified among a larger cohort of 609 patients who had either a new shunt or a newly changed distal terminus site. The authors present an analysis of this series, including a case of laparoscopy-assisted distal VGB shunt revision. RESULTS: The mean age at initial shunt placement was 5.1 months (range 3.0-9.4 months), with patients undergoing a mean of 11.8 shunt procedures (range 5-17) prior to the initial VGB shunt placement at a mean age of 5.3 years (range 7.9 months-12.8 years). All 6 patients with VGB shunt placement had hydrocephalus related to extreme prematurity (gestational age < 28 weeks). At the time of VGB shunt placement, all had complex medical and surgical histories, including poor venous access due to congenital or iatrogenic thrombosis or thrombophlebitis and a peritoneum hostile to distal shunt placement related to severe necrotizing enterocolitis. VGB complications included 1 case of shunt infection, identified at postoperative day 6, and 2 cases of distal shunt failure due to retraction of the distal end of the VGB shunt. In all, there were 3 conversions back to ventriculoperitoneal or ventriculoatrial shunts due to the 2 previously mentioned complications, plus 1 patient who outgrew their initial VGB shunt. Three of 6 patients remain with a VGB shunt, including 1 who underwent laparoscopy-assisted distal shunt revision 110.5 months after initial VGB shunt insertion. CONCLUSIONS: Placement of VGB shunts should be considered in the armamentarium of procedures that may be used in the particularly difficult cohort of children with hydrocephalus related to extreme prematurity. VGB shunts show utility as both a definitive treatment and as a "bridge" procedure until the patient is larger and comorbid abdominal and/or vascular issues have resolved sufficiently to allow conversion back to ventriculoperitoneal or ventriculoatrial shunts, if needed.

Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma.

Background: Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods: Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment. Results: Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%-97%). Conclusions: Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.

Successful Retreatment of a Child with a Refractory Brainstem Ganglioglioma with Vemurafenib.

A child with brainstem ganglioglioma underwent subtotal resection and focal radiation. Magnetic resonance imaging confirmed tumor progression 6 months later. Another partial resection revealed viable BRAF V600E-positive residual tumor. Vemurafenib (660 mg/m(2) /dose) was administered twice daily, resulting in >70% tumor reduction with sustained clinical improvement for 1 year. Vemurafenib was then terminated, but significant tumor progression occurred 3 months later. Vemurafenib was restarted, resulting in partial response. Toxicities included Grade I pruritus and Grade II rash. Vemurafenib was effectively crushed and administered in solution via nasogastric tube. We demonstrate benefit from restarting vemurafenib therapy.

Outcome of Transsphenoidal Surgery for Cushing Disease: A Single-Center Experience Over 32 Years.

BACKGROUND: Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness. OBJECTIVE: To analyze results of transsphenoidal surgery in 276 consecutive patients, including 19 children. METHODS: Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 µg/dL; type 2 = morning cortisol normal). RESULTS: Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths. CONCLUSION: Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.

Evans blue nanocarriers visually demarcate margins of invasive gliomas.

Aggressive surgical resection is the primary therapy for glioma. However, aggressive resection may compromise functional healthy brain tissue. Currently, there are no objective cues for surgeons to distinguish healthy tissue from tumor and determine tumor borders; surgeons skillfully rely on subjective means such as tactile feedback. This often results in incomplete resection and recurrence. The objective of the present study was to design, develop, and evaluate, in vitro and in vivo, a nanoencapsulated visible dye for intraoperative, visual delineation of tumor margins in an invasive tumor model. Liposomal nanocarriers containing Evans blue dye (nano-EB) were developed, characterized, and tested for safety in vitro and in vivo. 3RT1RT2A glioma cells were implanted into brains of Fischer 344 rats. Nano-EB or EB solution was injected via tail vein into tumor-bearing animals. To assess tumor staining, tissue samples were analyzed visibly and using fluorescence microscopy. Area, perimeter ratios, and Manders overlap coefficients were calculated to quantify extent of staining. Nano-EB clearly marked tumor margins in the invasive tumor model. Area ratio of nano-EB staining to tumor was 0.89 ± 0.05, perimeter ratio was 0.94 ± 0.04, Manders R was 0.51 ± 0.08, and M1 was 0.97 ± 0.06. Microscopic tumor border inspection under high magnification verified that nano-EB did not stain healthy tissue. Nano-EB clearly aids in distinguishing tumor tissue from healthy tissue in an invasive tumor model, while injection of unencapsulated EB results in false identification of healthy tissue as tumor due to diffusion of dye from the tumor into healthy tissue.

Utility of surveillance imaging after minor blunt head trauma.

OBJECT: Nonoperative blunt head trauma is a common reason for admission in a pediatric hospital. Adverse events, such as growing skull fracture, are rare, and the incidence of such morbidity is not known. As a result, optimal follow-up care is not clear. METHODS: Patients admitted after minor blunt head trauma between May 1, 2009, and April 30, 2013, were identified at a single institution. Demographic, socioeconomic, and clinical characteristics were retrieved from administrative and outpatient databases. Clinical events within the 180-day period following discharge were reviewed and analyzed. These events included emergency department (ED) visits, need for surgical procedures, clinic visits, and surveillance imaging utilization. Associations among these clinical events and potential contributing factors were analyzed using appropriate statistical methods. RESULTS: There were 937 admissions for minor blunt head trauma in the 4-year period. Patients who required surgical interventions during the index admission were excluded. The average age of the admitted patients was 5.53 years, and the average length of stay was 1.7 days; 15.7% of patients were admitted for concussion symptoms with negative imaging findings, and 26.4% of patients suffered a skull fracture without intracranial injury. Patients presented with subdural, subarachnoid, or intraventricular hemorrhage in 11.6%, 9.19%, and 0.53% of cases, respectively. After discharge, 672 patients returned for at least 1 follow-up clinic visit (71.7%), and surveillance imaging was obtained at the time of the visit in 343 instances. The number of adverse events was small and consisted of 34 ED visits and 3 surgeries. Some of the ED visits could have been prevented with better discharge instructions, but none of the surgery was preventable. Furthermore, the pattern of postinjury surveillance imaging utilization correlated with physician identity but not with injury severity. Because the number of adverse events was small, surveillance imaging could not be shown to positively influence outcomes. CONCLUSIONS: Adverse events after nonoperative mild traumatic injury are rare. The routine use of postinjury surveillance imaging remains controversial, but these data suggest that such imaging does not effectively identify those who require operative intervention.

Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres.

Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

Return to system within 30 days of pediatric neurosurgery.

OBJECT: Quality assessment measures have not been well developed for pediatric neurosurgical patients. This report documents the authors' experience in extracting information from an administrative database to establish the rate of return to system within 30 days of pediatric neurosurgical procedures. METHODS: Demographic, socioeconomic, and clinical characteristics were prospectively collected in administrative, business, and operating room databases. The primary end point was an unexpected return to the hospital system within 30 days from the date of a pediatric neurosurgical procedure. Statistical methods were used to identify clinical and demographic factors associated with the primary end point. RESULTS: There were 1358 pediatric neurosurgical procedures performed in the Children's Healthcare of Atlanta operating rooms in 2012, with 37.4% of these surgeries being preceded by admissions through the emergency department. Medicare or Medicaid was the payor for 54.9% of surgeries, and 37.6% of surgeries were shunt related. There were 148 unexpected returns to the system within 30 days after surgery, and in 109 of these cases, the patient had a presenting complaint that was attributable to the index surgery (related returns). The most common complaints were headache, nausea, vomiting, or seizure after shunt revision or cranial procedures (n = 62). The next most common reason for re-presentation was for wound concerns (n = 30). Thirty-seven of the 109 related returns resulted in a reoperation. The monthly rate of related returns was 8.1% ± 2.5% over the 12-month study period. When using related returns as the dependent variable, the authors found that patients who underwent a shunt-related surgery were both more likely to unexpectedly return to the system (OR 1.86, p = 0.008) and to require surgery upon readmission (OR 3.28, p = 0.004). Because an extended hospitalization shortened the window of time for readmission after surgery, extended length of stay was protective against return to system within 30 days of surgery. Importantly, if related and unrelated returns were analyzed together as the dependent variable (n = 148), no independent clinical and demographic risk factor could be identified. CONCLUSIONS: Quality assessment measures need to be clearly and carefully defined, as the definition itself will impact the analytical results. Clinicians must play a leading role in the development of these measures to ensure their clinical meaningfulness.

Diffuse leptomeningeal neuroepithelial tumor: 9 pediatric cases with chromosome 1p/19q deletion status and IDH1 (R132H) immunohistochemistry.

Leptomeningeal dissemination in children is typical of high-grade, and occasionally low-grade, neoplasms. Rare cases of widely disseminated oligodendroglia-like leptomeningeal tumors, sometimes with associated spinal cord lesions, have been described that respond to treatment and follow an indolent course. Whether these lesions represent an established tumor category or are a unique entity remains to be established. We present 9 pediatric cases of such diffuse leptomeningeal neuroepithelial tumors (DLNT), 8 with assessment of 2 common genetic alterations seen in oligodendrogliomas, 1p and 19q chromosomal deletions and isocitrate dehydrogenase-1 (IDH1) R132H mutations. Four patients were male and 5 female, with a mean age at presentation of 4 years (range, 2 to 7 y). All presented with signs of increased intracranial pressure and diffuse contrast enhancement of the leptomeninges by magnetic resonance imaging. Three had a cervical or upper thoracic spinal cord tumor, and another had a small cerebellar lesion. Leptomeningeal biopsies showed a thickened and fibrotic arachnoid infiltrated by monotonous cells with round nuclei and prominent perinuclear clearing. All cases were strongly immunoreactive for S100 protein, and most showed faint granular synaptophysin reactivity. Six of 8 cases showed deletions of chromosome arm 1p by fluorescence in situ hybridization, 2 of which also had loss of 19q. None of the lesions reacted with IDH1-R132H antibodies. Although the clinicopathologic features show overlap of these DLNT lesions with oligodendroglioma and extraventricular neurocytoma, they do not exactly match either one, suggesting that DLNTs are a distinct tumor entity.

The use of inside-outside screws for occipitocervical fusion in pediatric patients.

OBJECT: The authors describe the use of inside-outside occipital screws in 21 children with occipitocervical instability requiring occipitocervical fusion. METHODS: The ages of the patients were from 2 to 15 years, and patients presented with a variety of causes of occipitocervical instability, including congenital disorders, posttraumatic instability, idiopathic degeneration, and postoperative instability. Surgeries frequently included foramen magnum decompression, duraplasty, and laminectomy, but all patients required occipitocervical instrumentation and arthrodesis. Postoperative orthosis included the use of either a cervical collar or halo device. In all but one case, patients were followed postoperatively for at least 12 months. RESULTS: The mean age of patients was 9.93 years. Inside-outside screws were used in all reported cases. Rib autograft was used in all patients. In addition, demineralized bone matrix was used in 2 cases, and bone morphogenetic protein was used in 2 patients. Two patients required halo placement, and the other 19 were placed in cervical collars. The average time postoperative orthotics were used was 2.82 months. Arthrodesis was determined radiographically and was noted in all patients. No operative complications were noted; however, postoperative complications included 1 wound infection, 2 cases of hardware loosening, and the need for tracheostomy in 2 patients. CONCLUSIONS: Inside-outside screws were found to be a useful component of occipitocervical instrumentation in pediatric patients ranging from 2 to 15 years of age. Arthrodesis was demonstrated in all cases.

Transient enlargement of craniopharyngioma after radiation therapy: pattern of magnetic resonance imaging response following radiation.

Clinical experience suggests that craniopharyngiomas may temporarily increase in size after radiation therapy (RT). The study goal is to determine the incidence and natural history of this response in a cohort of patients managed at Children's Healthcare of Atlanta (CHOA) or Emory Healthcare (EHC). Between 08/1998 and 06/2009, 41 children and young adults were diagnosed with craniopharyngioma at CHOA and/or EHC. Of these, 21 received external-beam radiation and were included in our analysis. Serial magnetic resonance imaging (MRI) studies were evaluated volumetrically to assess response to RT. Median age at diagnosis was 8.2 years (range 3.2-23.5 years). Median radiation dose was 54.0 Gy using standard fractionation (1.8-2.0 Gy/day). With median follow-up of 41.3 months (range 7.2-121.8 months), actuarial local control and overall survival rates at 5 years were 78.7 % and 100 %, respectively. Of subjects, 52.4 % of subjects (11 of 21) were noted on serial MRI evaluation to have tumor enlargement (mostly cystic component) after radiation before eventual shrinkage without further intervention. For tumors that expanded, the median volume increase was 33.9 % (range 15.6-224.4 %). Median time to maximal tumor/cyst expansion was 1.5 months (range 1.0-5.0 months). Finally, nearly all patients (20 of 21) showed a measurable objective response to therapy by MRI regardless of ultimate disease control. Median time to maximal response post-radiation, as defined by MRI, was 9.5 months (range 3.5-39.9 months). In summary, RT is effective for managing craniopharyngioma. However, despite good ultimate responses, approximately 50 % of the patients show tumor/cyst expansion on MRI over the first few months post-radiation. Caution should be taken not to subject these patients to "salvage surgery" or cyst aspiration during this early time unless there are other overriding surgical indications. Understanding the natural history of this phenomenon could potentially help guide the management of these craniopharyngioma patients.

Imaging of idiopathic spinal cord herniation.

Idiopathic spinal cord herniation, unlike spinal cord herniation with a known traumatic or postoperative origin, is a relatively rare condition; however, it has been diagnosed and reported with increasing frequency in recent years. Such herniation most often occurs in the thoracic spine, between the T4 and T7 vertebrae. Brown-Séquard syndrome is the most frequently reported clinical feature. Early manifestations may include numbness and decreased temperature sensation in the legs, gait disturbances, pain, and incontinence. Symptoms often worsen over time, but timely diagnosis and treatment may allow the reversal of neurologic deficits. Surgical reduction typically is performed in patients with a history of symptom progression, but patients whose symptoms are less severe may be eligible for less invasive therapy and monitoring. Imaging features of spinal cord herniation generally include a dural tear through which a portion of the cord protrudes. Cerebrospinal fluid flows freely through the defect, causing increased turbulence in the fluid just dorsal to the site of herniation. The observation of this feature may allow the differentiation of spinal cord herniation from an arachnoid cyst. In addition, the calcification of nucleus pulposus leakage from a herniated disk may produce a linear area of hyperattenuation at computed tomography or signal hyperintensity at magnetic resonance imaging, an imaging feature known as the "nuclear trail" sign.

Peripheral nerve injuries in weight training: sites, pathophysiology, diagnosis, and treatment.

Direct trauma, compression caused by muscle hypertrophy or other soft tissue changes, or excessive stretching of a peripheral nerve in the upper extremity may lead to uncommon-but potentially serious-complications. Clinicians are seeing more of these injuries as weight training, power lifting, bodybuilding, cross-training, and general physical conditioning with weights become more popular. Symptoms of pain, weakness, paresthesia, or palsy; physical exam findings; electromyography; and nerve conduction studies are used to make the diagnosis. Most conditions respond well to conservative measures, such as rest from the offending exercise and correction of poor technique, but surgery may be required for complete clinical resolution in severe cases.