Carolina G. Benjamin

Mutant IDH1 and seizures in patients with glioma

Objective: Because the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1mut increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons. Methods: Three WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1mut status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5. Results: Preoperative seizures were observed in 18%–34% of IDH1 wild-type (IDH1wt) patients and in 59%–74% of IDH1mut patients (p < 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1mut was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6–3.9, p < 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-fold, but was completely blocked by AP5. Conclusions: The D2HG product of IDH1mut may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1mut gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1mut inhibitors may improve antiepileptic therapy in patients with IDH1mut gliomas.

Anaplastic pleomorphic xanthoastrocytoma with spinal leptomeningeal spread at the time of diagnosis in an adult

We describe the first patient, to our knowledge, with anaplastic pleomorphic xanthoastrocytoma (PXA) with spinal leptomeningeal spread at the time of diagnosis and present a review of the literature. PXA is a tumor that typically has an indolent course but occasionally, when anaplastic features are present, behaves in a more aggressive manner. We found that PXA with spinal leptomeningeal spread at the time of diagnosis confers a worse prognosis. Craniospinal imaging should be obtained at time of diagnosis of PXA and the presence of leptomeningeal spread may be indicative of a more aggressive disease process.

Minimally Invasive Posterior Cervical Fusion Techniques

Minimally invasive techniques were initially limited to decompressive procedures. Over time, these techniques have been adapted and can now be used for instrumentation and arthrodesis. Minimally invasive posterior cervical fusion can be used in the acute setting for traumatic conditions as well as for chronic degenerative cervical spondylotic myelopathy of the atlantoaxial and subaxial spine. In the properly selected patient, these techniques reduce approach-related complications, blood loss, and postoperative pain while preserving the efficacy of open posterior cervical fusions. Therefore, minimally invasive posterior cervical fusion should be a skill that all complex spine surgeons should be able to perform.

C-2 arteriovenous fistula presenting as a pathologic hangman's fracture: case report.

The authors report on an 81-year-old woman with a pathologic hangmans fracture secondary to a complex arteriovenous fistula (AVF). The patient presented with severe, unremitting neck pain and was found to have fractures bilaterally through the pars interarticularis of C-2 with significant anterior subluxation of C-2 over C-3 along with widening of the left transverse foramen. Due to an abnormally appearing left vertebral artery (VA) on CT angiography, the patient underwent conventional angiography, which revealed a complex AVF stemming from the left VA at the level of C-2 with dilated posterior cervical veins and a large venous varix. Given the radiographic evidence of bone remodeling and the chronicity of the AVF, it is believed that the C-2 vertebra was weakened over time by the pulsatile and compressive force of the vascular malformation eventually leading to fracture with minimal stress. Coil embolization of the AVF was performed followed by surgical fixation of C-1 to C-4. This case highlights the importance of investigating an underlying disease process in patients who present with significant spinal fractures in the absence of trauma.

Radiosurgery for dural arteriovenous malformations

Intracranial dural arteriovenous malformations (DAVFs) are relatively uncommon vascular lesions characterized by the direct connection of dural arteries into dural venous sinuses or leptomeningeal veins. Strategies for the treatment of these complex lesions have evolved significantly over the past three decades, and include open surgical disconnection, endovascular embolization, stereotactic radiosurgery (SRS), or a combination of these approaches. Radiosurgical intervention is unique in offering significant benefits to patients while exposing them to few of the risks associated with more invasive interventions. In this chapter we provide an overview of DAVFs and discuss the features of these lesions that affect management. We focus, in particular, on radiosurgical management of these lesions, describing present treatment paradigms, the procedure for the treatment of DAVFs with SRS, and expected clinical outcomes using SRS.