Intramedullary pediatric low-grade glioma of the spine.

PURPOSE: Pediatric intramedullary spinal cord low-grade gliomas (pLGGs) are rare diagnoses among central nervous system (CNS) tumors in the pediatric population. The classic presentation of the patients includes some degree of neurologic deficit, although many times the symptoms are vague which leads to delayed diagnosis. MATERIAL AND METHODS: The first step in the diagnosis includes special parameters in spinal imaging, particularly magnetic resonance imaging (MRI), and surgical resection remains the cornerstone for both diagnosis and treatment. Yet, recent years advancement in molecular and genetic understanding of CNS tumors allows for better adjustment of the treatment and follow-up regimens. Based on postoperative status, adjuvant therapy may provide additional therapeutic advantage for some types of tumors. CONCLUSION: Ultimately, patients have a very promising prognosis when treated appropriately in most of the cases of pediatric spinal cord LGG with continued advances arising. This manuscript summarizes the most contemporary evidence regarding clinical and treatment features of intramedullary pLGGs.

How modern treatments have modified the role of surgery in pediatric low-grade glioma.

Low-grade gliomas are the most common brain tumor of childhood, and complete resection offers a high likelihood of cure. However, in many instances, tumors may not be surgically accessible without substantial morbidity, particularly in regard to gliomas arising from the optic or hypothalamic regions, as well as the brainstem. When gross total resection is not feasible, alternative treatment strategies must be considered. While conventional chemotherapy and radiation therapy have long been the backbone of adjuvant therapy for low-grade glioma, emerging techniques and technologies are rapidly changing the landscape of care for patients with this disease. This article seeks to review the current and emerging modalities of treatment for pediatric low-grade glioma.

The role of neuromodulation in the management of drug-resistant epilepsy.

Drug-resistant epilepsy (DRE) poses significant challenges in terms of effective management and seizure control. Neuromodulation techniques have emerged as promising solutions for individuals who are unresponsive to pharmacological treatments, especially for those who are not good surgical candidates for surgical resection or laser interstitial therapy (LiTT). Currently, there are three neuromodulation techniques that are FDA-approved for the management of DRE. These include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Device selection, optimal time, and DBS and RNS target selection can also be challenging. In general, the number and localizability of the epileptic foci, alongside the comorbidities manifested by the patients, substantially influence the selection process. In the past, the general axiom was that DBS and VNS can be used for generalized and localized focal seizures, while RNS is typically reserved for patients with one or two highly localized epileptic foci, especially if they are in eloquent areas of the brain. Nowadays, with the advance in our understanding of thalamic involvement in DRE, RNS is also very effective for general non-focal epilepsy. In this review, we will discuss the underlying mechanisms of action, patient selection criteria, and the evidence supporting the use of each technique. Additionally, we explore emerging technologies and novel approaches in neuromodulation, such as closed-loop systems. Moreover, we examine the challenges and limitations associated with neuromodulation therapies, including adverse effects, complications, and the need for further long-term studies. This comprehensive review aims to provide valuable insights on present and future use of neuromodulation.

Intramedullary spinal cord tumors in pediatric patients presenting later with brain lesions: case series and systematic review of the literature.

PURPOSE: Intramedullary spinal cord tumors are an uncommon pathology in adults and children. Most descriptive studies of intramedullary spinal cord tumors have not focused on a possible association with future brain lesions. To the best of our knowledge, few reports describe this potential relationship. This is one of the most extensive case series of secondary brain lesions of intramedullary spinal cord tumors in the pediatric population. METHODS: Retrospective chart review was performed on pediatric patients (21 years old and younger) who underwent resection of an intramedullary spinal cord tumor at two tertiary care hospitals from 2001 to 2020. Patients previously treated or diagnosed with spinal cord tumor, and subsequent development of intracranial manifestation of the same or different tumor, were included. Data regarding epidemiology, surgical intervention, and clinical and follow-up course were gathered. Data analysis was performed according to a standardized clinical protocol with a literature review. RESULT: More than 500 patients underwent intradural spinal tumor resection surgeries at participating hospitals from 2001 to 2020. After excluding adult patients (older than 21 years old) and those with extramedullary lesions, 103 pediatric patients were identified who underwent resection of an intramedullary spinal cord tumor. Four underwent resection of an intermedullary tumor and later in their follow-up course developed a secondary intracranial neoplasm. In every case, the secondary neoplasm had the same pathology as the intramedullary tumor. Three of the patients had tumors at the cervico-thoracic junction, and one patient had a high cervical tumor. These patients had a negative primary workup for any metastatic disease at the time of the presentation or diagnosis. Complete and near complete resection was performed in three patients and subtotal in one patient. CONCLUSION: Secondary brain tumors disseminated after initial spinal cord tumor are extremely rare. This study aims to allow specialists to better understand these pathologies and treat these rare tumors with more certainty and better expectations of unusual associated lesions and conditions.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

The evolution of spinal cord surgery: history, people, instruments, and results.

INTRODUCTION: Spinal cord surgery has and always will be a challenging operation with satisfying results, but also with potentially devastating results. Over the last century, there has been an evolution in the way we perceive and conduct spinal cord surgery. The phenomenal evolution in technology from the very first x-ray pictures helps to localize the spinal pathology through the use of high-resolution MRI and ultrasonography that allows for high precision surgery with relatively minimal exposure. METHODS: The advancements in the surgical technique and the utilization of neuromonitoring allow for maximal safe resection of these delicate and intricate tumors. We also are beginning to understand the biology of spinal cord tumors and vascular lesions, as in the recent 2021 WHO classification which identifies specific entities such as spinal ependymomas, MYCN-amplified, as separate entity from the other subtypes of ependymomas. Surgeons have also accepted the importance of maximal safe resection for most of the spinal cord pathologies rather than just performing biopsy and adjuvant treatment. CONCLUSION: There have been significant advances since the first resection of an intramedullary tumor including diagnosis, imaging, and surgical technique for children. These advances have improved the prognosis and outcome in these children.

Accuracy and Utility of Frameless Stereotactic Placement of Stereoelectroencephalography Electrodes.

BACKGROUND: Successful surgery for epilepsy hinges on identification of the epileptogenic focus. Stereoelectroencephalography (sEEG) is the most effective way to identify most seizure foci. There are multiple methods of inserting depth electrodes, including frame-based, frameless, and robot-assisted techniques. Studies have shown the accuracy of frame-based and robotic-assisted techniques to be statistically similar, while only one study has detailed the frameless sEEG insertion technique. METHODS: Patients underwent placement of sEEG depth electrodes using frameless stereotaxy from September 2019 to September 2021 at Geisinger Medical Center by a single surgeon. Seizure history, electrode placement accuracy relative to the planned trajectories, surgical times, success rate of identifying the epileptogenic focus, and subsequent seizure control rates after surgical treatment were documented. RESULTS: Data were available for 21 patients and 181 electrodes inserted using the VarioGuide frameless stereotactic system. Each insertion took an average of 14.5 minutes per lead. Average entry variance was 2.7 mm with an average target variance of 4.6 mm. The epileptogenic focus was identified in 19 of 21 patients, and further surgical treatment was performed in 18 of 21 patients (85.7%). CONCLUSIONS: VarioGuide frameless stereotaxy for sEEG placement is comparable to frame-based and robotic-assisted techniques with statistically similar rates of epileptic focus identification. Lead placement accuracy is slightly lower and time per lead is slightly higher relative to robot-assisted surgeries. When a robot system is unavailable, surgeons can consider using a frameless stereotactic technique for sEEG insertion, allowing patients to benefit from a similarly high rate of epileptic zone identification.

Knowledge Review of Spinal Deformity and the Need for Fusion and Fixation following Treatment for Spinal Tumors among the Pediatric Age Group.

BACKGROUND: Spinal tumors are rare pathology in the pediatric population. The tumors can be classified as extradural, intradural extramedullary, or intramedullary. Any of the spinal tumors can eventually lead to spinal deformity. The progressive spinal deformity can be part of the initial presentation or evolve on long follow-up, even years after the initial intervention and treatment. SUMMARY: Management of spinal deformity associated with spinal tumors in children is not well defined. Patients with progressive symptoms and even neurological deficits need correction for their deformity when diagnosed. Patients that do not have pain or related neurological deficits should be evaluated for the severity of their deformity and followed long-term. Special consideration is needed for young patients who need multilevel surgery or have deformity at presentation. KEY MESSAGES: When considering the need for instrumentation and fusion, the surgeon should consider the age of the patient, expected future growth of the spine, neurologic status, extent of initial deformity, and the number of vertebral levels involved by tumor. Providers should also consider how surgery may fix or prevent deformity, especially when instrumentation can affect imaging at follow-up.

Malignant Spinal Tumors.

Malignant spinal tumors constitute around 22% of all primary spinal tumors. The most common location of metastases to the spinal region is the extradural compartment. The molecular and genetic characterization of these tumors was the basis for the updated WHO classification of CNS tumors in 2016, where many CNS tumors are now diagnosed according to their genetic profile rather than relying solely on the histopathological appearance. Magnetic resonance imaging (MRI) is the current gold standard for the initial evaluation and subsequent follow-up on intradural spinal cord tumors, and the imaging sequences must include T2-weighted images (WI), short time inversion recovery (STIR), and pre- and post-contrast T1-WI in the axial, sagittal, and coronal planes. The clinical presentation is highly variable and depends on the tumor size, growth rate, type, infiltrative, necrotic and hemorrhagic potential as well as the exact location within the spinal compartment. Surgical intervention remains the mainstay of management of symptomatic and radiographically enlarging spinal tumors, where the goal is to achieve maximal safe resection. Tumor recurrences are managed with repeat surgical resection (preferred whenever possible and safe), radiotherapy, chemotherapy, or any combination of these therapies.

Benign Spinal Tumors.

Benign spinal intradural tumors are relatively rare and include intramedullary tumors with a favorable histology such as low-grade astrocytomas and ependymomas, as well as intradural extramedullary tumors such as meningiomas and schwannomas. The effect on the neural tissue is usually a combination of mass effect and neuronal involvement in cases of infiltrative tumors. The new understanding of molecular profiling of different tumors allowed us to better define central nervous system tumors and tailor treatment accordingly. The mainstay of management of many intradural spinal tumors is maximal safe surgical resection. This goal is more achievable with intradural extramedullary tumors; yet, with a meticulous surgical approach, many of the intramedullary tumors are amenable for safe gross-total or near-total resection. The nature of these tumors is benign; hence, a different way to measure outcome success is pursued and usually depends on functional rather than oncological or survival outcomes.

Review and update on pediatric ependymoma.

Since our last Special Annual Issue dedicated to the topic of ependymoma in 2009, critical advancements have been made in the understanding of this disease which is largely confined to childhood. In the era of molecular profiling, the prior classification of ependymoma based on histology has become largely irrelevant, with multiple new subtypes of this disease now being described in the newest 2021 WHO CNS Tumor Classification System. Despite our advancements in understanding the underlying biology of these tumors, the mainstays of treatment-gross total surgical resection followed by confocal radiation therapy-have continued to yield the best treatment results across multiple studies and centers. Here, we provide an update on our understanding of the advancements made in tumor biology, surgical, and oncologic management of this disease. As we move into an era of more personalized medicine, it is critical to reflect on our historical understanding of different disease entities, to better understand the future directions of our treatments.

The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas.

OBJECTIVE: Intramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Anticipating a subependymoma on preoperative imaging can inform surgical decision-making and improve patient counseling. Here, we present our experience recognizing IMSC subependymomas on preoperative magnetic resonance imaging (MRI) based on a distinctive characteristic termed the "ribbon sign." METHODS: We retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The "ribbon sign" was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense tumor. The ribbon sign was confirmed by an expert neuroradiologist. RESULTS: MRIs from 151 patients were reviewed, including 10 patients with IMSC subependymomas. The ribbon sign was demonstrated on 9 (90%) patients with histologically proven subependymomas. Other tumor types did not display the ribbon sign. CONCLUSION: The ribbon sign is a potentially distinctive imaging feature of IMSC subependymomas and indicates the presence of spinal cord tissue between eccentrically located tumors. Recognition of the ribbon sign should prompt clinicians to consider a diagnosis of subependymoma, aiding the neurosurgeon in planning the surgical approach and adjusting the surgical outcome expectation. Consequently, the risks and benefits of gross-versus subtotal resection for palliative debulking should be carefully considered and discussed with patients.

Approaches to Incidental Intradural Tumors of the Spine in the Pediatric Population.

BACKGROUND: Incidental intradural tumors of the spine in the pediatric population are rare lesions whose management remains unclear. Surgeons must balance the risks of iatrogenic deficits and complications after surgical resection against the risks from progressive growth of the tumor. Moreover, the natural history of an incidental finding can be difficult to predict. Here, we review the literature on incidental intradural tumors of the spine and present considerations for their management. SUMMARY: Growth of the tumor or changes in radiographic features are usually indications for resection. Asymptomatic lesions can be found in patients with genetic syndromes that predispose to tumor formation, such as neurofibromatosis type 1 and 2, schwannomatosis, and Von-Hippel-Lindau syndrome, and careful workup of a genetic cause is warranted in any patient presenting with multiple tumors and/or cutaneous features. Close follow-up is generally favored given the heavy tumor burden; however, some recommend pre-emptive resection to prevent permanent neurological deficits. Incidental intradural tumors can also occur in association with hydrocephalus, significant syringomyelia, and cord compression, and surgical treatment is usually warranted. Tumors may also be discovered as part of the workup for scoliosis, where they are not truly incidental to the scoliosis but rather are contributing to curve deformation. KEY MESSAGES: Thorough workup of patients for associated genetic syndromes or comorbidities should be undertaken in pediatric patients with incidental intradural tumors. Further research is needed into the natural history of these incidental lesions. Incidental tumors can often be managed conservatively with close follow-up, with surgical intervention warranted for expanding tumors or new-onset symptoms.

Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics.

Intramedullary astrocytomas represent approximately 30%-40% of all intramedullary tumors and are the most common intramedullary tumor in children. Surgical resection is considered the mainstay of treatment in symptomatic patients with neurological deficits. Gross total resection (GTR) can be difficult to achieve as astrocytomas frequently present as diffuse lesions that infiltrate the cord. Therefore, GTR carries a substantial risk of new post-operative deficits. Consequently, subtotal resection and biopsy are often the only surgical options attempted. A midline or paramedian sulcal myelotomy is frequently used for surgical resection, although a dorsal root entry zone myelotomy can be used for lateral tumors. Intra-operative neuromonitoring using D-wave integrity, somatosensory, and motor evoked potentials is critical to facilitating a safe resection. Adjuvant radiation and chemotherapy, such as temozolomide, are often administered for high-grade recurrent or progressive lesions; however, consensus is lacking on their efficacy. Biopsied tumors can be analyzed for molecular markers that inform clinicians about the tumor's prognosis and response to conventional as well as targeted therapeutic treatments. Stratification of intramedullary tumors is increasingly based on molecular features and mutational status. The landscape of genetic and epigenetic mutations in intramedullary astrocytomas is not equivalent to their intracranial counterparts, with important difference in frequency and type of mutations. Therefore, dedicated attention is needed to cohorts of patients with intramedullary tumors. Targeted therapeutic agents can be designed and administered to patients based on their mutational status, which may be used in coordination with traditional surgical resection to improve overall survival and functional status.

Neurophysiologic monitoring during cervical traction in a pediatric patient with severe cognitive disability and atlantoaxial instability.

Background: Surgical management of atlantoaxial instability (AAI) in pediatric patients with Down syndrome is associated with high neurological morbidity. Moreover, Down syndrome cognitive impairment coupled to AAI removes traditional verbal communication to relay evolving symptoms and aid in neurologic examination. It is not clear whether surgical adjuncts can alter clinical outcomes in this vulnerable population. Case Description: Herein, we report the case of a 6-year-old patient with significant developmental delay and severe AAI that was successfully managed by stabilization with guidance of neurophysiologic investigations in the perioperative phase. Conclusion: Perioperative neurophysiologic monitoring is safe, useful, and reliable in pediatric patients with trisomy 21 undergoing cervical traction and occipitocervical instrumented fusion for AAI.

Posterior Fossa Tumours in the First Year of Life: A Two-Centre Retrospective Study.

Posterior fossa tumours (PFTs) in infants are very rare, and information on these tumours is scarce in the literature. This retrospective study reports their pathological characteristics and describes surgical aspects and treatment outcomes. A two-centre cohort of infants with PFTs treated from 2007 to 2018 was retrospectively reviewed. Patient characteristics, clinical, and treatment data were reviewed. Survival curves for progression-free survival (PFS) and overall survival (OS) were generated. Thirty-three infants were retrieved. There were 11 low grade and 22 high-grade tumours. The most common presenting symptom was intracranial hypertension. Fifteen children out of thirty-three progressed. Five-year PFS was significantly lower in children with high-grade tumours (38.3%) than those with low-grade tumours (69.3%), p = 0.030. High-grade pathology was the only predictor of progression (HR 3.7, 95% CI 1.1-13.31), p = 0.045. Fourteen children with high-grade tumours died, with a 5-year OS of 55.25%. PFTs in children below one year of age still represent a unique challenge. Infants with high-grade tumours display the worst outcomes and the lowest survival, indicating that more effective strategies are needed.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Pediatric mild head trauma: is outpatient follow-up imaging necessary or beneficial?

OBJECTIVE: Pediatric traumatic brain injury (TBI) is the leading cause of death among children and is a significant cause of morbidity. However, the majority of injuries are mild (Glasgow Coma Scale score 13-15) without any need for neurosurgical intervention, and clinically significant neurological decline rarely occurs. Although the question of repeat imaging within the first 24 hours has been discussed in the past, the yield of short-term follow-up imaging has never been thoroughly described. In this paper, the authors focus on the yield of routine repeat imaging for pediatric mild TBI (mTBI) at the first clinic visit following hospital discharge. METHODS: The authors conducted a retrospective review of patients with pediatric brain trauma who had been admitted to Johns Hopkins All Children's Hospital (JHACH). Patients with mTBI were identified, and their presentation, hospital course, and imaging results were reviewed. Those pediatric patients with mTBI who had undergone no procedure during their initial admission (only conservative treatment) were eligible for inclusion in the study. Two distinct groups were identified: patients who underwent repeated imaging at their follow-up clinic visit and those who underwent only clinical evaluation. Each case was assessed on whether the follow-up imaging had changed the follow-up course. RESULTS: Between 2010 and 2015, 725 patients with TBI were admitted to JHACH. Of those, 548 patients qualified for analysis (i.e., those with mTBI who received conservative treatment without any procedure and were seen in the clinic for follow-up evaluation within 8 weeks after the trauma). A total of 392 patients had only clinic follow-up, without any diagnostic imaging study conducted as part of their clinic visit, whereas the other 156 patients underwent repeat MRI. Only 1 patient had a symptomatic change and was admitted after undergoing imaging. For 30 patients (19.2%), it was decided after imaging to continue the neurosurgical follow-up, which is a change from the institutional paradigm after mTBI. None of these patients had a change in neurological status, and all had a good functional status. All of these patients had one more follow-up in the clinic with new MRI, and none of them required further follow-up. CONCLUSIONS: Children with mTBI are commonly followed up in the ambulatory clinic setting. The authors believe that for children with mTBI, normal clinical examination, and no new symptoms, there is no need for routine ambulatory imaging since the clinical yield of such is relatively low.