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 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.

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.

Outcomes of the early endoscopic-assisted suturectomy for treatment of multisuture craniosynostosis.

To present the outcomes and adverse events associated with the endoscopic-assisted, minimally invasive suturectomy in patients with multisuture synostosis. This retrospective cohort study included children < 65 days of age who underwent endoscopic-assisted suturectomy (EAS) for multisuture craniosynostosis at a single tertiary referral center from 2013 to 2021. The primary outcome was calvarial expansion, and the secondary outcome was adverse events. The pre- and post-operative 3-dimensional brain computed tomography (CT) scan was used to calculate the intracranial volume and cephalic index. During a period of 2 years, 10 infants (10-64 days) diagnosed with multisuture synostosis underwent single-stage EAS of every affected suture in our center. The coronal suture was the most prevalent involved suture among our cases. The mean age and weight of the patients were 39 ± 17.5 days and 4.39 ± 0.8 kg, respectively. The surgical procedure took 42 ± 17.4 min of time and caused 46 ± 25.4 mL of bleeding on average. Ninety percent of the operations were considered successful (n = 9) regarding calvarial expansion. There were two complications, one requiring an open vault surgery and one repairing a leptomeningeal cyst. In the eight patients who did not necessitate further interventions, the mean pre-operative intracranial volume was 643.3 ± 189.4 cm3. The follow-up results within the average of 38.9 months after surgery showed that as age increases, the intracranial volume also increased significantly (R: 0.6, P < 0.0001), which suggests continued skull growth in patients who underwent EAS. With the low rate of intra- or post-operative complications and promising results on revising the restricted skull sutures, EAS seems both a safe and effective therapeutic modality in patients with multisuture synostosis, especially if completed in the first months after birth.

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.

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.

Predictors of survival and time to progression following operative management of intramedullary spinal cord astrocytomas.

PURPOSE: Surgical resection is considered standard of care for primary intramedullary astrocytomas, but the infiltrative nature of these lesions often precludes complete resection without causing new post-operative neurologic deficits. Radiotherapy and chemotherapy serve as potential adjuvants, but high-quality data evaluating their efficacy are limited. Here we analyze the experience at a single comprehensive cancer center to identify independent predictors of postoperative overall and progression-free survival. METHODS: Data was collected on patient demographics, tumor characteristics, pre-operative presentation, resection extent, long-term survival, and tumor progression/recurrence. Kaplan-Meier curves modeled overall and progression-free survival. Univariable and multivariable accelerated failure time regressions were used to compute time ratios (TR) to determine predictors of survival. RESULTS: 94 patients were included, of which 58 (62%) were alive at last follow-up. On multivariable analysis, older age (TR = 0.98; p = 0.03), higher tumor grade (TR = 0.12; p < 0.01), preoperative back pain (TR = 0.45; p < 0.01), biopsy [vs GTR] (TR = 0.18; p = 0.02), and chemotherapy (TR = 0.34; p = 0.02) were significantly associated with poorer survival. Higher tumor grade (TR = 0.34; p = 0.02) and preoperative bowel dysfunction (TR = 0.31; p = 0.02) were significant predictors of shorter time to detection of tumor growth. CONCLUSION: Tumor grade and chemotherapy were associated with poorer survival and progression-free survival. Chemotherapy regimens were highly heterogeneous, and randomized trials are needed to determine if any optimal regimens exist. Additionally, GTR was associated with improved survival, and patients should be counseled about the benefits and risks of resection extent.

Complex craniosynostosis in the context of Carpenter's syndrome.

Carpenter's syndrome or acrocephalopolysyndactyly type II is a rare genetic autosomal recessive disease, with an incidence estimated at 1 per 1 million births. Common findings of a brachydactyly, polysyndactyly, and a trefoil-like skull with extreme brachycephaly due to fusion of the bilateral coronal, sagittal and lambdoid sutures. We report a 12-month-old male who was referred to our care for evaluation of a craniofacial deformity-a trefoil-like skull, flattened and receding forehead, bulging of temporal bones, hypertelorism, exorbitism, and polysyndactyly in the upper and lower limbs and psychomotor delay. Head computed tomography (CT) with 3D reconstruction revealed craniosynostosis with fusion of the coronal, metopic, and sagittal sutures. Correction of the craniofacial deformity was performed with satisfactory aesthesis of the craniofacial bones at 2 years of follow-up. Early correction of craniofacial deformity in Carpenter's syndrome is usually safe within 6 to 12 months. Venous drainage abnormalities and ectatic emissary veins can lead to significant bleeding and may be detected on MR angiography. Significant skull weakening may lead to bony fragmentation while creating cranial flaps and is best evaluated with 3D CT imaging. Taking these pitfalls into consideration decreases the chances of aborting the surgery and may lead to better overall outcomes.

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.

Spontaneous regression of multiple intracranial capillary hemangiomas in a newborn-long-term follow-up and literature review.

BACKGROUND: Intracranial capillary hemangiomas (ICHs) have a natural history and behavior that is very different from intracranial cavernous malformations. The literature is not consistent as to the best management strategy for ICHs. CASE DESCRIPTION: Our patient is a 40-day-old male infant who presented with progressive increase in head circumference and multiple cutaneous capillary and ICHs. Obstructive hydrocephalus necessitated urgent cerebrospinal fluid (CSF) diversion, but no other surgical intervention was pursued due to the high risk-to-benefit ratio. All intracranial lesions spontaneously regressed by 11 years of age, albeit at a slower speed than the cutaneous lesions, with no functional or cognitive sequelae. We conducted a comprehensive literature review and provided a summary of all reported ICH cases. CONCLUSION: Asymptomatic patients with ICHs are best approached with close follow-up and serial imaging studies as the potential for spontaneous regression is relatively high. Patients with isolated lesions or unclear diagnoses may benefit from a stereotactic biopsy, and surgical resection should be reserved for symptomatic lesions only.

Split cord malformation and tethered cord syndrome: case series with long-term follow-up and literature review.

PURPOSE: To date, the description of the natural course of concurrent tethered cord syndrome with a low-lying conus medullaris and split cord malformation is lacking in the literature. We report a cohort of adult and pediatric patients with concurrent malformations and long-term follow-up. METHODS: Patients with concurrent diagnoses of split cord malformation and tethered cord (radiographic evidence supporting clinical symptomatology) were identified between 2000 and 2020. Patients without sufficient documentation or at least 6-month follow-up were excluded. RESULTS: Nine patients were identified with an average of 8.9 years follow-up (range 2-31 years). The most common symptoms were radiating leg pain and lower extremity paresthesias, occurring in 44% of patients; and bladder/bowel dysfunction, worsening scoliosis, and acute motor deterioration were less common. Two patients were successfully treated conservatively for mild leg pain and paresthesias. For those who underwent surgery, all experienced symptomatic relief upon first follow-up. Two had late symptomatic recurrence; one 4 and 8 years after initial surgery; and the other, 11, 26, and 31 years after initial surgery. CONCLUSION: The rarity of concurrent split cord and tethered cord syndrome with a low-lying conus makes management difficult to formulate. This series supplements our knowledge of the long-term outcomes and lessons learned from the management of these patients. Approximately 25% of patients were managed conservatively and had symptomatic improvement. For surgically managed patients, with intractable pain or worsening neurological function, symptoms can still recur over a decade after intervention. Reoperation, however, can still be beneficial, can provide years of relief, and should be considered.

Percutaneous lumbar pedicle fixation in young children with flexion-distraction injury-case report and operative technique.

Thoracolumbar fractures in children are relatively uncommon and should be regarded as a separate entity from those in adults. While percutaneous pedicle fixation has emerged as an effective alternative to open fixation in adults with unstable thoracolumbar fractures, this technique is rarely applied in children. We report a 6-year-old girl with an L3 chance fracture, which was treated via short-segment percutaneous pedicle fixation. We also discussed the technical challenges and caveats of this surgical technique in young children. While potentially more challenging, percutaneous pedicle fixation is feasible in young children with thoracolumbar fractures. Specific differences between the developing and mature spine in regard to anatomical and biomechanical characteristics, including ligamentous laxity and intrinsic elasticity, should be taken into consideration. Future studies are needed to compare outcomes of minimally invasive spinal techniques to open surgery in children.

Exoscope aided trans-sulcal minimally invasive parafascicular resection of a paediatric brainstem pilocytic astrocytoma using a tubular retractor system.

The surgical management of brainstem glioma is challenging and has significant morbidity. Advances in surgical armamentarium has presented the opportunity to tackle these lesions. We present the case of a paediatric patient with a 2.3cm midbrain pilocytic astrocytoma. With the aid of tractography, neuro-navigation, 3-dimensional exoscope and a tubular retractor, near total resection of the tumour was achieved through a trans-sulcal para-fascicular approach without permanent injury to the corticospinal tract. To our knowledge this is the first report of a brainstem tumour resected using this approach and demonstrates what can be achieved with synergistic utility of evolving technologies in neurosurgery.

Scoliosis in patients with Chiari malformation type I.

The literature about the association between Chiari malformations (CMs) and scoliosis has been growing over the last three decades; yet, no consensus on the optimal management approach in this patient population has been reached. Spinal anomalies such as isolated syrinxes, isolated CM, and CM with a syrinx are relatively common among patients with presumed idiopathic scoliosis (IS), a rule that also applies to scoliosis among CM patients as well. In CM patients, scoliosis presents with atypical features such as early onset, left apical or kyphotic curvature, and neurological deficits. While spinal X-rays are essential to confirm the diagnosis of scoliosis among CM patients, a magnetic resonance imaging (MRI) is also recommended in IS patients with atypical presentations. Hypotheses attempting to explain the occurrence of scoliosis in CM patients include cerebellar tonsillar compression of the cervicomedullary junction and uneven expansion of a syrinx in the horizontal plane of the spinal cord. Early detection of scoliosis on routine spinal examination and close follow-up on curve stability and progression are essential initial steps in the management of scoliosis, especially in patients with CM, who may require full spine MRI to screen for associated neuro-axial anomalies; bracing and spinal fusion may be subsequently pursued in high-risk patients.

Use of computer-assisted design and manufacturing to localize dural venous sinuses during reconstructive surgery for craniosynostosis.

OBJECTIVE: Cranial vault remodeling surgery for craniosynostosis carries the potential risk of dural venous sinus injury given the extensive bony exposure. Identification of the dural venous sinuses can be challenging in patients with craniosynostosis given the lack of accurate surface-localizing landmarks. Computer-aided design and manufacturing (CAD/CAM) has allowed surgeons to pre-operatively plan these complex procedures in an effort to increase reconstructive efficiency. An added benefit of this technology is the ability to intraoperatively map the dural venous sinuses based on pre-operative imaging. We utilized CAD/CAM technology to intraoperatively map the dural venous sinuses for patients undergoing reconstructive surgery for craniosynostosis in an effort to prevent sinus injury, increase operative efficiency, and enhance patient safety. Here, we describe our experience utilizing this intraoperative technology in pediatric patients with craniosynostosis. METHODS: We retrospectively reviewed the charts of children undergoing reconstructive surgery for craniosynostosis using CAD/CAM surgical planning guides at our institution between 2012 and 2016. Data collected included the following: age, gender, type of craniosynostosis, estimated blood loss, sagittal sinus deviation from the sagittal suture, peri-operative outcomes, and hospital length of stay. RESULTS: Thirty-two patients underwent reconstructive cranial surgery for craniosynostosis, with a median age of 11 months (range, 7-160). Types of synostosis included metopic (6), unicoronal (6), sagittal (15), lambdoid (1), and multiple suture (4). Sagittal sinus deviation from the sagittal suture was maximal in unicoronal synostosis patients (10.2 ± 0.9 mm). All patients tolerated surgery well, and there were no occurrences of sagittal sinus, transverse sinus, or torcular injury. CONCLUSIONS: The use of CAD/CAM technology allows for accurate intraoperative dural venous sinus localization during reconstructive surgery for craniosynostosis and enhances operative efficiency and surgeon confidence while minimizing the risk of patient morbidity.

Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord.

Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.