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

Radiation-induced intracranial osteosarcoma of the anterior skull base after treatment of esthesioneuroblastoma

Esthesioneuroblastoma (ENB) is an uncommon sinonasal cancer of the olfactory neuroepithelium that is typically treated with surgical resection followed by radiation therapy. Radiation-induced intracranial osteosarcoma of the skull base is a rare but devastating long-term complication of radiation therapy in this region. Here, we present a case of an 82-year-old patient who developed radiation-induced osteosarcoma of the anterior skull base and paranasal sinuses 10 years after radiation therapy following resection of an ENB. Older patients may be at risk of developing this complication earlier and with a worse prognosis relative to younger patients. Treating physicians/surgeons should be aware of this devastating complication. Patients who are treated with high-dose radiation therapy in this region should be followed for many years.</jats:p

Cervical spondylodiscitis caused by <i>Candida albicans</i> in a non-immunocompromised patient: A case report and review of literature

Background: Fungal cervical spondylodiscitis is rare and accounts for less than 1% of all cervical, thoracic, and lumbar vertebral osteomyelitis and discitis. Case Description: A 32-year-old non-immunocompromised male presented with persistent neck pain and paresthesias. The magnetic resonance imaging of the cervical spine demonstrated a contrast-enhancing erosive lesion involving the cervical C6 and C7 vertebral bodies accompanied by epidural phlegmon. Blood culture was negative. The patient underwent a C6 and C7 anterior corpectomy with instrumented fusion (e.g., expandable cage C5 to T1). Intraoperatively, frank pus was noted within the C6-C7 disc space and was accompanied by thick prevertebral and epidural phlegmon extending from C5 to T1. Intraoperative cultures grew Candida albicans. Three days later, a C6-C7 laminectomy with C4-T2 posterior instrumented fusion was performed; the cultures again grew C. albicans. The patient was treated with intravenous micafungin for 14 days followed by 6–12 months of 400 mg oral fluconazole daily. Conclusion: There are few cases in literature where non-immunocompromised patients developed fungal cervical spondylodiscitis. Prompt diagnosis and appropriate management are critical to effectively treat these patients. Surgical intervention may warrant corpectomy, discectomy, and operative debridement followed by long-term targeted antifungal therapy. </jats:sec

Pediatric Moyamoya Syndrome Secondary to Tuberculous Meningitis

ObjectivesTuberculosis is uncommon in the United States and a rare cause of meningitis in children with severe neurologic consequences. Tuberculous meningitis (TBM) is an even rarer cause of moyamoya syndrome with only a handful of cases previously reported.MethodsWe report the case of a female patient who initially presented at 6 years of age with TBM and developed moyamoya syndrome requiring revascularization surgery.ResultsShe was found to have basilar meningeal enhancement and right basal ganglia infarcts. She was treated with 12 months of antituberculosis therapy and 12 months of enoxaparin and maintained on daily aspirin indefinitely. However, she developed recurrent headaches and transient ischemic attacks and was found to have progressive bilateral moyamoya arteriopathy. At age 11 years, she underwent bilateral pial synangiosis for the treatment of her moyamoya syndrome.DiscussionMoyamoya syndrome is a rare but serious sequalae of TBM and may be more common in pediatric patients. The risk of stroke may be mitigated by pial synangiosis or other revascularization surgeries in carefully selected patients.</jats:sec

In vitro measurement of the permeability of endovascular coils deployed in cerebral aneurysms

Background and purposeAneurysm recurrence is the primary limitation of endovascular coiling treatment for cerebral aneurysms. Coiling is currently quantified by a volumetric porosity measure called packing density (pd). Blood flow through a coil mass depends on the permeability of the coil mass, and not just its pd. The permeability of coil masses has not yet been quantified. Here we measure coil permeability with a traditional falling-head permeameter modified to incorporate idealized aneurysms.MethodsSilicone replicas of idealized aneurysms were manufactured with three different aneurysm diameters (4, 5, and 8 mm). Four different coil types (Codman Trufill Orbit, Covidien Axium, Microvention Microplex 10, and Penumbra 400) were deployed into the aneurysms with a target pd of 35%. Coiled replicas were installed on a falling-head permeameter setup and the time taken for a column of fluid above the aneurysm to drop a certain height was recorded. Permeability of the samples was calculated based on a simple modification of the traditional permeameter equation to incorporate a spherical aneurysm.ResultsThe targeted 35% pd was achieved for all samples (35%±1%, P=0.91). Coil permeabilities were significantly different from each other (P&lt;0.001) at constant pd. Microplex 10 coils had the lowest permeability of all coil types. Data suggest a trend of increasing permeability with thicker coil wire diameter (not statistically significant).ConclusionsA simple in vitro setup was developed to measure the permeabilities of coil masses based on traditional permeametry. Coil permeability should be considered when evaluating the hemodynamic efficacy of coiling instead of just packing density. Coils made of thicker wires may be more permeable, and thus less effective, than coils made from thinner wires. Whether aneurysm recurrence is affected by coil wire diameter or permeability needs to be confirmed with clinical trials.</jats:sec

The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies

Despite advances in surgical resection and chemoradiation, high-grade brain tumors continue to be associated with significant morbidity/mortality. Novel therapeutic strategies and approaches are, therefore, desperately needed for patients and their families. Given the success experienced in treating multiple other forms of cancer, immunotherapy and, in particular, immunovirotherapy are at the forefront amongst novel therapeutic strategies that are currently under investigation for incurable brain tumors. Accordingly, herein, we provide a focused mini review of pertinent oncolytic herpes viruses (oHSV) that are being investigated in clinical trials

The Current Landscape of Oncolytic Herpes Simplex Viruses as Novel Therapies for Brain Malignancies

Despite advances in surgical resection and chemoradiation, high-grade brain tumors continue to be associated with significant morbidity/mortality. Novel therapeutic strategies and approaches are, therefore, desperately needed for patients and their families. Given the success experienced in treating multiple other forms of cancer, immunotherapy and, in particular, immunovirotherapy are at the forefront amongst novel therapeutic strategies that are currently under investigation for incurable brain tumors. Accordingly, herein, we provide a focused mini review of pertinent oncolytic herpes viruses (oHSV) that are being investigated in clinical trials.</jats:p

Ruptured Suprasellar Dermoid Cyst Treated With Lumbar Drain to Prevent Postoperative Hydrocephalus: Case Report and Focused Review of Literature

Background: Ruptured intracranial dermoid cysts are extremely rare. Standard treatment consists of endonasal decompression or craniotomy with evacuation and copious irrigation of subarachnoid spaces to remove any disseminated cystic contents. Disseminated fat particles in the subarachnoid space may be the cause of further sequalae, including the subsequent development of chemical meningitis and hydrocephalus. Here, we present a case of ruptured suprasellar dermoid cyst treated with craniotomy for emergent optic nerve decompression, followed by postoperative hydrocephalus successfully treated with lumbar drain.Case description: We describe a 30-year-old man with a history of migraines who presented with acute onset of headache, photophobia, nausea, vomiting, and vision loss in the left eye. Head CT and brain MRI demonstrated a ruptured suprasellar dermoid cyst with associated mass effect on the optic nerves and frontal lobes as well as fat attenuation material within the subarachnoid spaces. The patient underwent left frontotemporal craniotomy for cyst resection and developed non-obstructive hydrocephalus on postoperative day 1, refractory to external ventricular drainage. Placement of a lumbar drain cleared the subarachnoid space of debris derived from the ruptured dermoid cyst, and the hydrocephalus resolved. The patient did not require permanent CSF diversion.Conclusions: Intracranial dermoid cysts are uncommon, and rupture is a rare event. Standard surgical treatment with craniotomy for evacuation may leave disseminated dermoid contents and fat particles throughout the subarachnoid spaces. We highlight a case of ruptured suprasellar dermoid cyst with postoperative communicating hydrocephalus treated with lumbar drain when external ventricular drain (EVD) was ineffective. Review of the current literature reveals inconsistent findings on the effects of remaining fat particles. In cases with clinical evidence of increased intracranial pressure due to non-obstructive hydrocephalus attributable to chemical meningitis, temporary lumbar drainage is an option to be considered before committing the patient to permanent shunting.</jats:p