Julia R Schneider

Lesional Temporal Lobe Epilepsy: Beware the Deceitful “Panic Attack”

BACKGROUND Ganglioglioma is a rare, benign, intraaxial glioneuronal tumor but a relatively common cause of pharmacoresistant temporal lobe epilepsy (TLE). Given its often nonspecific neuropsychiatric manifestations and frequently negative electroencephalographic workup, TLE can be easily misdiagnosed as a psychiatric disorder, particularly panic attacks. CASE DESCRIPTION We present a case of a 17-year-old boy who was found to have lesional TLE secondary to a left temporal ganglioglioma, 5 years after having been misdiagnosed with panic disorder and having undergone ineffective and unnecessary psychotherapy. He was successfully cured by surgery. Although a few similar cases of TLE masquerading as a panic disorder have been previously reported in the literature, this is the youngest and only pediatric patient described to date. CONCLUSION This report underscores the challenges in making an accurate clinical diagnosis of TLE and the importance of timely brain imaging whenever an atypical or medically refractory panic disorder is encountered.

Neuroradiological and Neuropathological Changes After 177Lu-Octreotate Peptide Receptor Radionuclide Therapy of Refractory Esthesioneuroblastoma

BACKGROUND AND IMPORTANCE Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB. CLINICAL PRESENTATION A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease. CONCLUSION We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.

Lessons Learned Using a High-Definition 3-Dimensional Exoscope for Spinal Surgery

BACKGROUND The operative microscope has significantly advanced modern neurosurgical spine surgery but continues to be limited by high costs, suboptimal optics, poor ergonomics, and difficulties with maneuverability. We believe the novel 4K high-definition (4K-HD) 3-dimensional (3D) exoscope (EX), may improve the surgical corridor through advancements in illumination, ergonomics, magnification, and depth of field and has the potential to be utilized in neurosurgical education and training. OBJECTIVE To evaluate the surgical potential of a novel 3D EX system in spinal surgery. METHODS Retrospective analysis over 6 mo of all patients who have undergone spinal surgery at Northwell Health using the 3D EX. Nuances of surgical theater positioning, advantages/disadvantages of the EX and clinical sequelae of the patients were analyzed. RESULTS All 10 patients who underwent spinal surgery utilizing the EX experienced excellent surgical and clinical outcomes without complications. The low-profile EX allowed for excellent operative corridors and instrument maneuverability. The large monitor also resulted in an immersive surgical experience, and gave team members the same 3D vision as the operator. CONCLUSION This study demonstrates the feasibility of utilizing the 3D 4K-HD EX system and highlights potential technical assets of this novel technology in regard to optics, ergonomics, and maneuverability. Further clinical research is needed to examine the clinical effectiveness of the EX system for different surgical approaches through quantitative methodology.

Local Immunotherapy for Malignancy: A Role for Brain Tumors?

Local Immunotherapy for Malignancy: A Role for Brain Tumors? Mounting evidence suggests that the immune system can be reprogrammed for cancer eradication. Utilization of personalized antigen-specific targets is limited due to the heterogenic nature of tumors. Programming pre-existing T-cells within the tumor microenvironment to recognize and attack cancer may be a more reliable and applicable immunotherapy treatment method for tumors. Commonly, T cells that recognize tumor antigens are often tipped toward immunosuppression in established tumors, with T cell inhibitory receptor activation rather than stimulatory receptor activation.1 In this novel paper, the authors focus on relieving the negative checkpoints and stimulation of activation pathways on T cells as a novel therapeutic technique.2 Sagiv-Barfi et al2 developed a new immunotherapy by directly injecting immune activating agents into the tumor, in situ vaccination, using the tumor and its immune reactive microenvironment as an antigen source. A screening strategy for candidate immune-stimulatory agents revealed unmethylated CG-enriched oligodeoxynucleotide (CpG), a Tolllike receptor 9 ligand, could induce the expression of OX40 on CD4 + T cells in the tumor microenvironment. OX40 is a costimulatory molecule of the TNFR superfamily, and notably with activation can promote T cell activation. Furthermore, they utilized an agonistic anti-OX40 antibody to provide a synergistic stimulus to elicit an antitumor immune response. The strategy was to implant the same syngeneic tumor at two separate sites in vivo, followed by injection of the test agents, CpG and OX40 antibody, locally in one of the tumor sites. Remarkably, they demonstrate in situ vaccination with a CpG induces OX40 expression in intratumoral CD4 + T cells, as shown by flow cytometry and positron emission tomography. This effect was reproduced in a patient with follicular lymphoma treated with low-dose radiation and intratumoral injection of CpG. The effects of CpG signal to T cells appear to be dependent on myeloid-derived cell communication, emphasizing the necessity of antigen-presenting cells in the local environment. Using an A20 B cell lymphoma model, they show that in situ vaccination of CpG and an agonistic OX 40 antibody resulted in regression of tumor at both local and distant tumor sites and required the presence of both CD4+ and CD8+ T cells. In situ vaccination was shown to not only be effective against transplanted syngeneic models of lymphoma, breast carcinoma, colon cancer, and melanoma but also in a genetically driven spontaneous model of breast cancer. They establish that the low doses of these agents work by triggering an immune response in the microenvironment of the injected site rather than by diffusion of the injected agents to distal sites. Mechanistically, it seems that the therapeutic effect of systemic in situ vaccination occurs through a combination of natural killer cell activation, Treg inhibition, Teff activation all at the treated tumor site.2 These preclinical studies provide a strong rationale for translation of combinatory usage of CpG with anti-OX40 antibodies from the bench to bedside. Clinically, CpG is being investigated for clinical trial use, either as a single agent or concomitantly with other therapeutic modalities for the treatment of lymphoma. Similarly, anti-OX40 antibody is being studied in early phase clinical trials for the treatment of lymphoma, carcinoma, sarcoma, and metastatic disease.2 The authors provide evidence for combination therapy using a TLR agonist and an OX-40 antibody to activate the T cell immune repertoire within the tumor microenvironment. It is feasible that this technique could be utilized for the treatment of brain tumors intraoperatively as the situ vaccination does not require prior knowledge of the tumor antigens. Furthermore, direct injection of the tumor, with low doses of these agents, can help avoid side effects from systemic administration.3 Another potential application would be to administer the in situ vaccine at the site of the primary tumor for those patients with intracranial metastatic disease in combination withmultimodality chemoradiation treatment.