Autologous Cell Immunotherapy (IGV-001) with IGF-1R Antisense Oligonucleotide in Newly Diagnosed Glioblastoma Patients

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety

Posterior Transdural Approach for a Calcified Thoracic Intradural Disc Herniation Using a 3-Dimensional Exoscope: 2-Dimensional Operative Video

This video depicts the removal of an intradural thoracic disc herniation through a purely transdural approach. Thoracic disc herniations are rare, and less than 5% are intradural. Though thoracic disc herniations are removed through a posterolateral or transthoracic corridor, there is literature to support a transdural approach for central herniations.1-3 Although the transdural approach has been selectively adopted for central soft herniations, calcified herniations have been regarded as less suitable.1,2 Intradural thoracic herniations have not been specifically addressed by a transdural approach in the limited literature, though it has been utilized in conjunction with a larger transthoracic approach.4 Our case features a 72-yr-old female presenting with worsening left leg weakness. Computed tomography (CT) identified a multilobulated ventral calcified mass at T11-12. Magnetic resonance imaging was not possible because of an incompatible pacemaker. Our impression was that this likely represented an intradural meningioma though a calcified intradural disc herniation was considered. Given the apparent intradural location, we opted for a transdural approach only via T11-12 laminectomy and a midline dural opening. Dentate ligament sectioning allowed a clear corridor to the now apparent disc material. Postoperative CT confirmed near complete resection, and the patient showed neurological improvement. Ultimately, the transdural approach alone led to complete discectomy while avoiding the morbidity of an invasive transthoracic approach and instrumented fusion. To our knowledge, this is the first video documenting a purely transdural approach for resection of an intradural disc herniation. The patient consented to the surgical procedure and to the use of intraoperative video for education purposes

Bilateral cerebral infarction in the setting of pituitary apoplexy: a case presentation and literature review

Pituitary tumor apoplexy (PTA) is a potentially fatal condition caused by hemorrhage and rapid expansion of a pituitary tumor. One rare consequence of PTA is occlusion of the intracavernous carotid arteries, very rarely leading to cerebral infarction.To describe a case of PTA leading to bilateral cerebral infarction and provide an extensive literature review of all previously reported cases of PTA leading to cerebral infarction. We discuss how these cases contribute to our understanding of the management of PTA, and we also discuss the differences between cases associated with the reported mechanism of carotid occlusion (compression vs. vasospasm).A 56-year-old previously healthy woman complained of severe headache and visual loss one day after sustaining a fall from standing. Computed tomography demonstrated an enlarged sellar and suprasellar mass displacing both cavernous ICAs laterally, with multiple bilateral hypodense areas in the ICA distribution consistent with infarction. She clinically deteriorated and underwent endoscopic transsphenoidal gross total resection for suspected PTA within 48 hours after falling. Her prognosis remained poor after 5 days, and support was withdrawn.Twenty-four cases of PTA leading to cerebral infarction have been previously documented—four bilateral, our case being the fifth. Based on our review, the presence of infarction itself does not seem to warrant surgical management in the absence of previously established indications for surgery (such as a deteriorating visual field), despite a 3–5 times mortality increase. No conclusion regarding the role of the mechanism of occlusion can be made at this time

Oncolytic Virus in Gliomas: A Review of Human Clinical Investigations

Gliomas remain one of the more frustrating targets for oncologic therapy. Glioma resistance to conventional therapeutics is a product of their immune-privileged milieu behind the blood-brain barrier, in addition to their suppressive effect on the immune response itself. Taking the lead from the growing success of immunotherapy for systemic cancers, such as lung cancer and melanoma, immunotherapeutics has emerged as a major player in the potential treatment of gliomas, with oncolytic viruses in particular showing significant promise as evidenced by the recent Breakthrough and Fast Tract Designations for PVSRIPO and DNX2401. This review serves as a useful and updated compendium of the completed human clinical investigations for several oncolytic viruses in the treatment of gliomas

The role of stereotactic radiosurgery in the treatment of intramedullary spinal cord neoplasms: a systematic literature review

Advances in imaging technology and microsurgical techniques have made microsurgical resection the treatment of choice in cases of symptomatic intramedullary tumors. The use of stereotactic radiosurgery (SRS) for spinal tumors is a recent development, and its application to intramedullary lesions is debated. We conducted a literature search through PubMed's MeSH system, compiling information regarding intramedullary neoplasms treated by SRS. We compiled histology, tumor location and size, treatment modality, radiation dose, fractionation, radiation-induced complications, follow-up, and survival. Ten papers reporting on 52 patients with 70 tumors were identified. Metastatic lesions accounted for 33%, while 67% were primary ones. Tumor location was predominantly cervical (53%), followed by thoracic (33%). Mean volume was 0.55 cm(3) (95% confidence interval (CI), 0.26-0.83). Preferred treatment modality was CyberKnife® (87%), followed by Novalis® (7%) and linear particle accelerator (LINAC) (6%). Mean radiation dose was 22.14 Gy (95% CI, 20.75-23.53), with mean fractionation of 4 (95% CI, 3-5). Three hemangioblastomas showed cyst enlargement. Symptom improvement or stabilization was seen in all but two cases. Radionecrotic spots adjacent to treated areas were seen at autopsy in four lesions, without clinical manifestations. Overall, clinical and radiological outcomes were favorable. Although surgery remains the treatment of choice for symptomatic intramedullary lesions, SRS can be a safe and effective option in selected cases. While this review suggests the overall safety and efficacy of SRS in the management of intramedullary tumors, future studies need randomized, homogeneous patient populations followed over a longer period to provide more robust evidence in its favor

Intraventricular Choroid Plexus Cavernoma Resection Using Tubular Retractor System and Exoscope Visualization: A Technical Case Report

BACKGROUND AND IMPORTANCE: Cavernous malformations (CMs) account for approximately 5% to 10% of all CNS vascular malformations, and intraventricular CMs (IVCMs) are a rare subtype, accounting for 2.5% to 10.8% of all intracranial CMs. IVCMs can expand rapidly, leading to compression of adjacent structures, intraventricular hemorrhage, and obstructive hydrocephalus. Diagnosis is challenging because it can mimic a variety of other lesions. CLINICAL PRESENTATION: A 71-year-old man presented after a fall because of imbalance. MRI of the head showed a homogenously enhancing 2-cm mass in the posterior aspect of the right lateral ventricle, with blood layering in the right occipital horn and adjacent parietal edema and leptomeningeal enhancement, as well as a pituitary lesion. DISCUSSION: The patient underwent a right parietal craniotomy for resection of the mass. The ventricle was accessed through a transsulcal approach through the intraparietal sulcus using a tubular retractor system. The mass was arising from the choroid plexus and dissected free in a piecemeal fashion. Postoperative imaging confirmed gross total resection, and the patient had an uneventful recovery. CONCLUSION: Here, we present the first case of a choroid plexus IVCM removed using a tubular retractor system. We demonstrate that this is a safe and effective approach for this rare lesion given the minimal traction on brain parenchyma and enhanced visualization of a deep-seated cavernoma in the lateral ventricle

A Case of Pituitary Apoplexy and Cavernous Sinus Syndrome during Hemodialysis

Background. Pituitary apoplexy (PA) is a clinical syndrome of pituitary hemorrhage or infarction and can result in hypopituitarism as well as compression of adjacent brain structures. Visual loss occurs frequently, as a result of tumor expansion and compression of the optic chiasm and optic nerves. Additionally, with pituitary tumor invasion into the fixed space of the cavernous sinus, compression of multiple cranial nerves can result in cavernous sinus syndrome (CSS). We describe a case of an undiagnosed pituitary tumor manifesting as abrupt PA with CSS during hemodialysis (HD). Clinical Case. A 77-year-old male with end-stage renal disease (ESRD) presented with acute onset of severe headache, decreased vision, ophthalmoplegia of the left eye, and hypotension during HD. MRI of the brain revealed a 2.5 cm pituitary adenoma with acute hemorrhage, compression of the left prechiasmatic optic nerve, and invasion into the left cavernous sinus (CS). The hormonal profile was consistent with multiple pituitary hormone deficiencies. The patient was treated with glucocorticoids and underwent transsphenoidal resection of the tumor. He had an uneventful postoperative hospital course, and his left visual acuity stabilized, although there was no immediate improvement in his other ocular symptoms. Conclusion. Our case highlights a rare constellation of a pituitary adenoma with CS invasion complicated by PA and CSS during HD. The pathophysiology of PA is not well understood, and there are very limited data regarding PA in patients with end-stage renal disease (ESRD) on HD. Prompt recognition of PA in a patient presenting with CSS, particularly in the HD setting, is essential to ensure appropriate care is provided for this medical emergency

Epidermoid tumors of the temporal lobe as epileptogenic foci

Intracerebral epidermoid tumors of the temporal lobe are exceedingly rare. The vast majority of these slow-growing tumors remain clinically silent while only a select few are associated with overt symptomatology. We report two patients with epidermoid tumors whose unique location in the temporal lobe resulted in secondarily generalized seizures. Our first patient, a 19-year-old female, presented with a secondarily generalized tonic–clonic seizure and MRI revealed a superior temporal lobe lesion that was subsequently treated with an awake craniotomy and gross total resection. Our second patient was a 71-year-old male with a recent seizure history and known left temporal lobe lesion. The patient underwent craniotomy for gross total resection of the mass. In these two patients, we found that MRI proved diagnostic and surgical resection was curative. Our clinical experience and review of the literature indicate that gross total resection of these lesions confers control of localization-related epilepsy