The Evolving Classification of Meningiomas: Integration of Molecular Discoveries to Inform Patient Care.

Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart's description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication and predict response to therapy. Precise and accurate classification is essential to optimizing management for patients with meningioma, which involves surveillance imaging, surgery, primary or adjuvant radiotherapy, and consideration for clinical trials. Currently, the World Health Organization (WHO) grade, extent of resection (EOR), and patient characteristics are used to guide management. While these have demonstrated reliability, a substantial number of seemingly benign lesions recur, suggesting opportunities for improvement of risk stratification. Furthermore, the role of adjuvant radiotherapy for grade 1 and 2 meningioma remains controversial. Over the last decade, numerous studies investigating the molecular drivers of clinical aggressiveness have been reported, with the identification of molecular markers that carry clinical implications as well as biomarkers of radiotherapy response. Here, we review the historical context of current practices, highlight recent molecular discoveries, and discuss the challenges of translating these findings into clinical practice.

Outcomes following stereotactic radiosurgery for foramen magnum meningiomas: a single-center experience and systematic review of the literature.

OBJECTIVE: Foramen magnum meningiomas (FMMs) pose a unique challenge given their intimate anatomical relationship with the craniovertebral junction. While resection has been studied extensively, much less has been reported about the use of stereotactic radiosurgery (SRS) for FMMs. This study includes what is to the authors' knowledge the first systematic review in the literature that summarizes patient and treatment characteristics and synthesizes outcomes following SRS for FMMs. METHODS: A retrospective chart review was conducted at a single major academic institution, and a systematic review was performed according to PRISMA guidelines. The initial search on the PubMed and Scopus databases yielded 530 results. Key data extracted from both databases included Karnofsky Performance Status (KPS) score and neurological deficits at presentation, tumor location, treatment indication, target volume, single versus multiple fractions, marginal and maximum doses, isodose line, clinical and radiographic follow-up times, and primary (clinical stability and local control at last follow-up) and secondary (mortality, adverse radiation events, time to regression, progression-free survival) outcomes. RESULTS: The study patients included 9 patients from the authors' institution and 165 patients across 4 studies who received SRS for FMMs. The weighted median age at treatment was 60.2 years, and 73.9% of patients were female. Common presenting symptoms included headache (33.9%), dizziness/ataxia (29.7%), cranial nerve deficit(s) (27.9%), numbness (22.4%), weakness (15.2%), and hydrocephalus (4.2%). Lateral/ventrolateral (64.2%) was the most common tumor location. SRS was utilized as the primary therapy in 63.6% of patients and as salvage (21.8%) or adjuvant (14.5%) therapy for the rest of the patients. Most patients (91.5%) were treated with a single fraction. A tumor with a weighted median target volume of 2.9 cm3 was treated with a weighted median marginal dose, maximum dose, and isodose line of 12.9 Gy, 22.8 Gy, and 58%, respectively. Clinical stability and local control at last follow-up were achieved in 98.8% and 97.0% of patients, respectively. Only one possible adverse radiation event occurred, and no mortality directly related to the tumor or SRS was reported. CONCLUSIONS: In this retrospective analysis and systematic review, the authors demonstrate SRS to be an effective and safe treatment option for carefully selected patients with FMMs.

Meningeal defects and focal cortical dysplasia: an unrecognized relationship? Illustrative case.

BACKGROUND: Focal cortical dysplasias (FCDs) are a heterogenous cluster of histopathologic entities classically associated with medically refractory epilepsy. Because there is substantial histopathologic variation among different types of FCD, there are likely multiple pathogenic mechanisms leading to these disorders. The meninges are known to play a role in cortical development, and disruption of meningeal-derived signaling pathways has been shown to impact neurodevelopment. To our knowledge, there has not yet been an investigation into whether genetic pathways regulating meningeal development may be involved in the development of FCD. OBSERVATIONS: The authors reported a patient with refractory epilepsy and evidence of FCD on imaging who received surgical intervention and was found to have an unusual dural anomaly overlying a region of type Ic FCD. To the authors' knowledge, this was the first report describing a lesion of this nature in the context of FCD. LESSONS: The dural anomaly exhibited by the patient presented what could be a potentially novel pathogenic mechanism of FCD. Resection of the cortical tissue underlying the dural anomaly resulted in improvement in seizure control. Although the pathogenesis is unclear, this case highlighted the importance of further investigation into the developmental origins of FCD, which may help elucidate whether a connection between meningeal development and FCD exists.

A Systematic Review of Outpatient Telemedicine Use in Neurosurgery Since the Start of Coronavirus Disease 2019.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has sparked interest in telemedicine, resulting in an increase in neurosurgical publications focused on it. We summarize this new literature to evaluate telemedicine applications to neurosurgery. METHODS: A systematic literature review was performed in accordance with the PRISMA guidelines by searching PubMed, Embase, and Scopus for journal articles published after January 1, 2020. All journal articles that included data after the start of COVID-19 and evaluated any aspect of telemedicine relevant to outpatient neurosurgical visits were included. The premise and key findings of each included study were extracted, as well as patient and provider satisfaction with and preference for telemedicine. RESULTS: Thirty-seven articles met the inclusion criteria. Four studies proposed and evaluated a remote neurologic examination. Two studies reported similar postvisit outcomes between remote and in-person visits. Twenty-four studies reported a combination of patient and provider opinions toward telemedicine. Of 9834 patients and 116 providers, 82.4% and 65.2% were satisfied overall with telemedicine, respectively. Of 3526 patients and 168 providers, 57.0% and 66.5% preferred telemedicine to in-person visits, respectively. CONCLUSIONS: Overall, most patients and providers have a high opinion of telemedicine for outpatient visits, and increasing evidence suggests that remote visits yield favorable clinical outcomes. The high rates of patient and provider satisfaction and preference may be considered for further adoption of remote neurosurgical visits beyond the COVID-19 era.

The role of neurosurgery in the management of tuberous sclerosis complex-associated epilepsy: a systematic review.

OBJECTIVE: Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem neurocutaneous disorder associated with cortical tubers, brain lesions seen in nearly all patients with TSC, which are frequently epileptogenic. Seizures are often the earliest clinical manifestation of TSC, leading to epilepsy in over 70% of patients. Medical management with antiepileptic drugs constitutes early therapy, but over 50% develop medically refractory epilepsy, necessitating surgical evaluation and treatment. The objective of this study was to summarize the literature and report seizure outcomes following surgical treatment for TSC-associated epilepsy. METHODS: A systematic literature review was performed in accordance with the PRISMA guidelines. The PubMed and Embase databases were searched for journal articles reporting seizure outcomes following epilepsy surgery in TSC patients. Included studies were placed into one of two groups based on the surgical technique used. Excellent and worthwhile seizure reductions were defined for each group as outcomes and extracted from each study. RESULTS: A total of 46 studies were included. Forty of these studies reported seizure outcomes following any combination of resection, disconnection, and ablation on a collective 1157 patients. Excellent and worthwhile seizure reductions were achieved in 59% (683/1157) and 85% (450/528) of patients, respectively. Six of these studies reported seizure outcomes following treatment with neuromodulation. Excellent and worthwhile seizure reductions were achieved in 34% (24/70) and 76% (53/70) of patients, respectively. CONCLUSIONS: Surgery effectively controls seizures in select patients with TSC-associated epilepsy, but outcomes vary. Further understanding of TSC-associated epilepsy, improving localization strategies, and emerging surgical techniques represent promising avenues for improving surgical outcomes.

Pediatric spinal intramedullary anaplastic myxopapillary ependymoma: a case report.

A 6-year-old girl presented with a 1-week history of progressive upper and lower extremity weakness and bilateral upper extremity dysesthesia. Imaging demonstrated a 4.7 × 1.2-cm enhancing intramedullary lesion in the cervical spine from level C2 to C5 with associated cystic components and syringomyelia. The patient underwent a C2-C5 laminoplasty, with gross total resection of the intramedullary lesion. Histological analysis showed small to medium-sized epithelioid cells, with predominantly a solid architecture focally infiltrating into the adjacent spinal cord tissue. Focal papillary differentiation was present along with peri-vascular pseudorosettes, mucin microcysts, and globules of dense collagen. Focal anaplasia was noted with mitosis (5/10 HPF), focal necrosis, and elevated Ki67 10-15%. These findings were consistent with a myxopapillary ependymoma with anaplastic features. CSF cytology was negative for tumor cells. MYCN amplification was not present. She was treated with targeted proton-beam radiation therapy. This is the fourth case of an intramedullary anaplastic myxopapillary ependymoma to date, and the first case in the cervical spine reported in the literature.

Radiation Induced Cavernomas in the Treatment of Pediatric Medulloblastoma: Comparative Study Between Proton and Photon Radiation Therapy.

Radiation induced cavernomas among children with medulloblastoma are common following external beam radiation (XRT) treatment with either photon or proton beams. However, with the increased utilization of proton beam therapy over the last decade we sought to determine if there was any difference in the development or natural history of these cavernous malformations (CM) or CM-like lesions. We performed a retrospective analysis of 79 patients from 2003 to 2019 who had undergone resection of medulloblastoma and subsequent XRT (30 photon or 49 proton beam therapy). The average age of patients at radiation treatment was 8.7 years old. Average follow up for patients who received photon beam therapy was 105 months compared to 56.8 months for proton beam therapy. A total of 68 patients (86.1%) developed post-radiation CMs, including 26 photon and 42 proton patients (86.7% and 85.7% respectively). The time to cavernoma development was significantly different, with a mean of 40.2 months for photon patients and 18.2 months for proton patients (p = 1.98 x 10-4). Three patients, one who received photon and two who received proton beam radiation, required surgical resection of a cavernoma. Although CM or CM-like lesions are detected significantly earlier in patients after receiving proton beam therapy, there appears to be no significant difference between the two radiation therapy modalities in the development of significant CM requiring surgical resection or intervention other than continued follow up and surveillance.

Infratentorial choroid plexus tumors in children.

OBJECTIVE: Choroid plexus tumors (CPTs) are rare pediatric intracranial neoplasms, and mostly occur in the lateral ventricle. CPTs located in the infratentorial location are considered to be rare in the pediatric population. We present a series of eight patients treated in the last decade at our institution focusing on clinical presentations and their outcome after excision. METHODS: We performed an institutional retrospective review of patients who underwent surgical resection of infratentorial CPTs during the period from 2008 to 2017. Patients' charts were reviewed for demographic data, clinical presentation, surgical treatment, and follow-up. RESULTS: There were eight patients (6 females and 2 males), with mean age for the cohort at presentation was 9.0 years. They represent 75% of 12 CPTs of all locations treated at the same period in our institution. These 8 infratentorial CPTs were in the fourth ventricle in seven, and in the cerebellopontine angle (CPA) in one. Seven patients had choroid plexus papillomas (WHO grade I) and 1 had an atypical choroid plexus papilloma (WHO grade II). Gross total resection was attempted in all patients. However, two of 3 patients with fourth ventricle floor invasion had subtotal resection with a thin layer of tumor left on the floor. The remaining 6 had a gross total resection. Six patients with preoperative hydrocephalus had a perioperative external ventricular drainage but none required permanent shunting after tumor resection. None showed recurrence/tumor progression without adjuvant therapy during the follow-up period of 20 months to 11 years. CONCLUSION: Infratentorial dominance among pediatric CPTs in this series contradicts previous reports. Infratentorial CPTs are amenable to surgical resection. Unresected small residuals due to invasion to the fourth ventricle floor showed no regrowth during 2 to 3 years follow-up without adjuvant therapy. However, these patients with incomplete resection need watchful observations.

Robotic Tissue Manipulation and Resection in Spine Surgery.

Spine surgery has evolved from the advent of imaging and navigation guidance, particularly with the rise of robotic surgical assistance. Navigation guidance has demonstrated potential for increased accuracy of transpedicular screw placement and resecting primary and metastatic spinal tumors. Robotic surgery is widely accepted in other surgical fields because laparoscopic techniques applied to robots can increase operator dexterity and improve visualization. Robotic assistance with spinal tumors has enjoyed rising interest owing to the potential for safe and minimally traumatic resection. We discuss available robots used for navigation-guided transpedicular screw placement and state-of-the-art robotic techniques for spinal or paraspinal tumor resection.