Syndrome of anterior neural stalk, vertebral abnormality, enteric duplication cyst, and diaphragmatic hernia related to persistent ventral neurenteric canal: report of two cases.

PURPOSE: Abnormalities in notochordal development can cause a range of developmental malformations, including the split notochord syndrome and split cord malformations. We describe two cases that appear related to unusual notochordal malformations, in a female and a male infant diagnosed in the early postnatal and prenatal periods, which were treated at our institution. These cases were unusual from prior cases given a shared constellation of an anterior cervicothoracic meningocele with a prominent "neural stalk," which coursed ventrally from the spinal cord into the thorax in proximity to a foregut duplication cyst. METHODS: Two patients with this unusual spinal cord anomaly were assessed clinically, and with neuroimaging and genetics studies. RESULTS: We describe common anatomical features (anterior neural stalk arising from the spinal cord, vertebral abnormality, enteric duplication cyst, and diaphragmatic hernia) that support a common etiopathogenesis and distinguish these cases. In both cases, we opted for conservative neurosurgical management in regards to the spinal cord anomaly. We proposed a preliminary theory of the embryogenesis that explains these findings related to a persistence of the ventral portion of the neurenteric canal. CONCLUSION: These cases may represent a form of spinal cord malformation due to a persistent neurenteric canal and affecting notochord development that has rarely been described. Over more than 1 year of follow-up while managed conservatively, there was no evidence of neurologic dysfunction, so far supporting a treatment strategy of observation.

Surgical Management in Herpes Simplex Encephalitis: Illustrative Case Report and Systematic Review of the Literature.

BACKGROUND: Herpes simplex virus (HSV) is a common cause of viral encephalitis and can result in refractory seizures. Although HSV encephalitis (HSVE) is treated primarily with acyclovir, surgery can play a role in medically intractable cases. OBJECTIVE: To systematically review cases describing surgery for the treatment of severe HSVE. We also present an illustrative case of anterior temporal lobectomy (ATL) for refractory status epilepticus in a patient with unilateral HSVE. This case demonstrates one clinical context in which surgery can be a useful adjunct. METHODS: We performed a systematic review using PubMed and Google Scholar, including case reports and series describing surgical interventions for HSVE. Clinical data were extracted from 54 publications that incorporated 67 patient cases. RESULTS: Surgical decompression occurred at a wide range of times after the onset of illness, although most patients were operated on 4 or more days after HSVE symptoms began. Numerous reports indicated that decompressive craniectomy, temporal lobectomy, and hematoma removal could treat intractably elevated intracranial pressure because of HSVE with favorable long-term outcomes. We describe an additional case in which a 52-year-old woman with HSVE developed refractory right temporal lobe seizures. After ATL, the seizures resolved with significant clinical improvement. CONCLUSION: Surgical treatment can be a useful adjunct for treatment of HSVE. There is substantial variability in the timing of surgical decompression in patients with HSVE, which can be necessary up to approximately 3 weeks after illness onset. ATL should be considered for refractory status epilepticus in HSVE with a unilateral seizure focus.

Immunotherapy approaches for the treatment of diffuse midline gliomas.

Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy has emerged as a promising alternative treatment modality. This review summarizes the various immunotherapy-based treatments for DMG as well as their specific limitations. We explore the use of cell-based therapies, oncolytic virotherapy or immunovirotherapy, immune checkpoint inhibition, and immunomodulatory vaccination strategies, and highlight the recent clinical success of anti-GD2 CAR-T therapy in diffuse intrinsic pontine glioma (DIPG) patients. Finally, we address the challenges faced in translating preclinical and early phase clinical trial data into effective standardized treatment for DMG patients.

Intracranial Facial Schwannomas: Multiple Distinct Entities Necessitating Tailored Management.

OBJECTIVE: Facial nerve (FN) schwannomas are extremely rare. According to their origin and involved segment(s), they constitute distinct subtypes. Intact FN function presents a management challenge, particularly in the cerebellopontine angle cisternal subtype that masquerades as a vestibular schwannoma. Fascicular-sparing technique with subtotal resection can maintain a good FN function. This study focuses on management to maintain good FN function. METHODS: A retrospective analysis of a cohort of 13 patients harboring FN schwannoma. Patient demographics, clinical findings, imaging, surgical intervention, and outcomes were analyzed. RESULTS: Five women and 8 men, with an average age of 55.3 years (39-75 years), harbored 6 cisternal, 2 ganglion, and 5 combined tumors. Average tumor size was 28.3 mm (16-50 mm). Eleven patients underwent surgery. Seven patients had fascicle-sparing technique, 5 of whom maintained their preoperative FN function, whereas 2 patients with near-total removal had a deterioration in FN function. Two patients with preoperative complete facial paralysis had gross total removal with interposition nerve graft. CONCLUSIONS: FN schwannomas management is individualized according to the subtype and the FN function at presentation. When FN function is normal, observation can be applied for prolonged period of time. At the early sign of deterioration, sub- or near-total resection with fascicle sparing technique can be performed. The cisternal subtype masquerade as vestibular schwannoma and should be recognized at the initial exposure by the appearance of finely splayed nerve fascicles at the perimetry of the tumor which elicits a motor response at low threshold stimulation.

Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells.

Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by the lack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment in GBM patients. In this study, we show the detection of cell surface death receptor (DR) target on CD146-enriched circulating tumor cells (CTC) captured from the blood of mice bearing GBM and patients diagnosed with GBM. Next, we developed allogeneic "off-the-shelf" clinical-grade bifunctional mesenchymal stem cells (MSCBif) expressing DR-targeted ligand and a safety kill switch. We show that biodegradable hydrogel encapsulated MSCBif (EnMSCBif) has a profound therapeutic efficacy in mice bearing patient-derived invasive, primary and recurrent GBM tumors following surgical resection. Activation of the kill switch enhances the efficacy of MSCBif and results in their elimination post-tumor treatment which can be tracked by positron emission tomography (PET) imaging. This study establishes a foundation towards a clinical trial of EnMSCBif in primary and recurrent GBM patients.

Multimodality resection of Oliveira Type IIIC* cerebellar AVM: A distinct entity.

Background: Posterior fossa AVMs constitute about 10% of AVMs and are associated with a higher rate of hemorrhage and increased morbidity and mortality rates necessitating treatment with rare exception. Cerebellar AVMs differ markedly from their supratentorial counterparts in that there are no perforating vessels involvement, drainage into the deep cerebral venous system, or presence of eloquent functional area except for the dentate nucleus. While Yasargil has classified cerebellar AVMs into seven subtypes according to their location, de Oliveira et al. have classified them using a more impactful grading system based on the size, location, and involvement of the dentate nucleus with the highest risk being III (size over 4 cm) C (mixed superficial and deep location) * (dentate involvement). In this extensive AVM with multiple arterial feeders from the SCA, AICA, and PICAs, preoperative embolization facilitates the safe surgical removal. Case Description: We present the case of resection of de Oliveira et al. IIIC* cerebellar AVM highlighting the tenets of preoperative embolization, wide surgical exposure with an extended retrosigmoid approach, arachnoidal dissection of the SAC, AICA, and PICA feeders, parenchymal dissection with preservation of the dentate nucleus, and preservation of venous drainage until complete disconnection. The patient consented to surgery after presenting with hemorrhage and developed hydrocephalus and CSF leak, managed successfully. Conclusion: de Oliveira et al. classification is highly impactful in grading posterior fossa AVMs.

Cerebellar High-Grade Glioma: A Translationally Oriented Review of the Literature.

World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) isocitrate dehydrogenase (IDH) wildtype glioblastoma (~43%). The latter had an unusually low-frequency of epidermal growth factor receptor (EGFR) and high-frequency of platelet-derived growth factor receptor alpha (PDGFRA) amplification, reflecting a different composition of methylation classes compared to supratentorial IDH-wildtype tumors. These new classifications have begun to reveal insights into the pathogenesis of HGG in the cerebellum and lead toward individualized treatment targeted toward the appropriate subclass of cHGG. Emerging therapeutic strategies include targeting the mitogen-activated protein kinases (MAPK) pathway and PDGFRA, oncolytic virotherapy, and immunotherapy. HGGs of the cerebellum exhibit biological differences compared to sHGG, and improved understanding of their molecular subclasses has the potential to advance treatment.

Foramen Magnum Meningioma-The Attainment of the Intra-Arachnoidal Dissection: 2-Dimensional Operative Video.

Ventral foramen magnum meningiomas are a forbidding lesion. The stake is so high with a risk of devastating paralysis and respiratory failure. Careful preoperative clinical and radiological evaluation is necessary to implement the best treatment plan. Successful surgical intervention depends on paying high attention to minute details throughout the case, from intratracheal intubation to extubation. The neural head-on-neck position is critical to avoid further medullary compression at intubation and positioning.1 Extensive neurophysiological monitoring, including somatosensory, motor, brainstem evoked potential, and cranial nerves, during the positioning and throughout the case, is extremely helpful to detect early signs of dysfunction.1 To expose and access ventral tumors, partial condyle resection and vertebral artery transposition are invaluable techniques.2,3 Preservation and minute manipulation of the vital neurovascular structures at this junction that includes the medullar, anterior spinal artery, posterior inferior cerebellar artery, vertebral junction perforators, and lower cranial nerves are essential for good outcomes. This is achieved by microsurgical intra-arachnoidal dissection under high magnification and after debulking the tumor to establish that plane.1,3,4 The demonstration of this technique is the purpose of this article. We demonstrate these surgical tenets applied to the resection of a large ventral foramen magnum meningioma extending from the midclivus to the C3 vertebral body level in a 54-yr-old female presenting with swallowing difficulties. The patient consented to the surgical intervention and the publication of her images. Image at 1:38 reprinted with permission from Al-Mefty O, Operative Atlas of Meningiomas. Vol 1, © LWW, 1998.

Integration of Microanatomy, Neuronavigation, Dynamic Neurophysiologic Monitoring, and Intraoperative Multimodality Imaging for the Safe Removal of an Insular Glioma: 2-Dimensional Operative Video.

Insular gliomas are located amongst myriad critical neurovascular structures, including lenticulostriate vessels, long insular perforators, putamen, internal capsule, frontal and temporal opercula, and key fasciculi.1-6 Each of these critical structures engenders key function of the brain, which must be preserved. Although anatomic knowledge remains the cornerstone of insular glioma surgery, novel tools have been developed to aid the surgeon in identifying and preserving these essential structures. Modern surgery of the insular glioma calls for seamless integration of these techniques to maximize the safety and totality of insular glioma resection, which has been shown to improve length of survival and seizure control, while reducing risk of tumor transformation.7-10 Neuronavigation can be used to help plan the craniotomy to achieve adequate exposure and assist during tumor resection. Brain "shift" can be corrected by re-registration following intraoperative magnetic resonance imaging (MRI). Interval ultrasound imaging reflects real-time progressive tumor resection. Dynamic neurophysiologic monitoring using thresholding techniques guides the surgeon as he resects tumor at its depth and posterior pole-close to the internal capsule. Intraoperative magnetic resonance imaging depicts residual infiltrative tumor that may require additional resection. The patient is a 33-yr-old woman with progressive growth of a right insular tumor and has consented to surgery, photography, and video recording. Figure at 1:57, © Ossama Al-Mefty, used with permission.

Transcavernous Resection of an Upper Clival Chondrosarcoma: "Cavernous Sinus as a Route": 2-Dimensional Operative Video.

Complete resection of skull base chondrosarcomas offers the potential for a durable, or even lifelong, cure and is best achieved at the first surgery.1,2 When a skull base chondrosarcoma is located at the upper clivus and in the interpeduncular cistern and invading laterally toward the petrous apex and cavernous sinus, the traditional approaches, ie, endonasal endoscopic or middle fossa approaches, are not adequate for the exposure and resection. The transcavernous sinus approach has been utilized to remove tumor from the cavernous sinus and as a corridor to the interpeduncular cistern and upper clivus, originally described for the clipping of basilar apex aneurysms. We present a case of a chondrosarcoma centered in the upper clivus and eroding the right posterior clinoid, analogous to the location of a giant basilar apex aneurysm. Detailed study of the tumor extension, bony invasion, and relationship with neuroanatomy dictated the most effective surgical approach.3,4 Neuronavigation and intraoperative magnetic resonance imaging (MRI) facilitated the gross total resection of the tumor in the Advanced Multimodality Image-Guided Operating (AMIGO) suite. Achieving a gross total tumor removal of this World Health Organization (WHO) grade I chondrosarcoma, adjuvant irradiation can be withheld1 and the patient monitored with serial imaging. The patient did well after the surgery. The patient consented for surgery and the use of photography.