D-TERMINED, a phase 1 trial in newly diagnosed high-grade glioma with temozolomide, radiation, and minocycline followed by adjuvant minocycline/temozolomide.

Background: Standard treatment for newly diagnosed high-grade gliomas remains suboptimal. Preclinical data indicate that mesenchymal transition and radiation resistance in glioblastoma are driven by NF-κB and microglia activation, which can be inhibited by minocycline. We assessed the safety and efficacy of minocycline combined with standard radiation and temozolomide in newly diagnosed high-grade gliomas. Methods: Adults with newly diagnosed high-grade glioma were eligible. Minocycline was given with concurrent and adjuvant temozolomide. Minocycline doses were escalated using a 3 + 3 design and expanded to identify the maximum tolerated dose (MTD) and adverse event profile. Individual progression-free survival (PFS) was compared to predicted PFS based on RTOG RPA class using a binomial test. The relationships between mesenchymal and microglial biomarkers were analyzed with immunohistochemistry. Results: The MTD of minocycline was 150 mg twice per day (N = 20); 1 patient (5%) experienced CTCAE grade 3 + nausea and dizziness, and 2 patients (10%) demonstrated thrombocytopenia requiring temozolomide interruptions. Twelve patients exceeded their predicted PFS (60%), which did not meet the predefined efficacy endpoint of 70%. Symptoms increased during post-radiation treatment but remained mild. No significant correlation was seen between biomarkers and PFS. Expression levels of P-p65, a marker of NF-κB activation, were correlated with the microglia marker IBA-1. Conclusions: Minocycline at 150 mg twice per day is well tolerated with standard chemoradiation in patients with newly diagnosed high-grade gliomas. PFS was not significantly increased with the addition of minocycline when compared to historical controls. NF-κB activation correlates with microglia levels in high-grade glioma.

Pearls & Oy-sters: ATX-FGF14 Mimicking Autoimmune Pathology.

ATX-FGF14 (formerly spinocerebellar ataxia 27, OMIM #193003) is an autosomal dominant condition caused by a pathogenic variant in the fibroblast growth factor 14 (FGF14, OMIM #601515) gene located on chromosome 13. The phenotypic expression can vary in patients with the same genotype, often delaying diagnosis, especially in probands without known affected relatives and/or with limited available family history. We describe 2 cases of ATX-FGF14 in 1 family with a focus on the importance of differentiating episodic manifestations of neurogenetic conditions from inflammatory/autoimmune neurologic conditions. A 68-year-old male patient (case 1) presented with episodic dysarthria, dizziness, imbalance, and encephalopathy, creating suspicion for a possible autoimmune etiology. At the first evaluation, the patient reported no significant family history. Four years later, on revisiting the family history, he noted that his 49-year-old niece (case 2) had also developed neurologic symptoms of an unclear etiology. On evaluation, she had tremor and ataxia. Both patients also had coexistent evidence of systemic autoimmunity that likely contributed to the initial suspicion of neurologic autoimmunity, and neither had cerebellar or brainstem volume loss. Ultimately, their genetic testing revealed a pathogenic structural variant in the FGF14 gene, consistent with ATX-FGF14. These 2 cases highlight the importance of a detailed interval family history at each visit, especially in undiagnosed adult patients, as well as the importance of objectively analyzing the impact of immunotherapy diagnostic treatment trials to avoid unnecessary immunomodulatory medications.

Conventional and Advanced Imaging of Spinal Cord Tumors.

Spinal cord tumors are best identified by conventional MR imaging with contrast. Most intramedullary spinal cord tumors have characteristic MR imaging features that allow an accurate preoperative diagnosis. The spinal cord tumors reviewed in this article include the most common tumors, ependymomas and astrocytomas, as well as the less common tumors such as hemangioblastomas and metastases. Rare tumors such as primary CNS lymphoma and melanocytic tumors are also described. Advanced imaging techqniques of more common intramedullary tumors are also reviewed.

GABA-A Receptor Encephalitis After Autologous Hematopoietic Stem Cell Transplant forMultiple Myeloma: Three Cases and Literature Review.

BACKGROUND AND OBJECTIVES: The relationship between autologous hematopoietic stem cell transplant (aHSCT) for multiple myeloma (MM) and anti-GABAA receptor (GABAAR) encephalitis is unknown. We aimed to describe the clinical features, diagnostic process, and outcome of 3 cases of anti-GABAAR encephalitis in patients with a history of prior aHSCT for MM. METHODS: A case series of 3 patients. Anti-GABAAR antibody was tested at the University of Pennsylvania Laboratory. RESULTS: The patients were all male, aged 52 (case 1), 61 (case 2), and 62 (case 3) years at encephalitis symptom onset. The duration between completion of aHSCT and the onset of encephalitis was 43, 18, and 9 months, respectively. All 3 patients presented with new seizures and altered cognitive function. Other symptoms included headache and visual obscurations in cases 1 and 2 and intractable vertigo and mania in case 3. Brain MRI demonstrated nonenhancing multifocal T2-weighted/fluid-attenuated inversion recovery cortical and subcortical hyperintensities in all 3 patients. Cases 2 and 3 underwent brain biopsy before initiating immunomodulatory therapy, which demonstrated nonspecific encephalitis with astrogliosis in the white matter; these 2 patients were started on immunotherapy for the treatment of anti-GABAAR encephalitis after 22 days and 3 months, respectively, from the first presentation. Case 1 was started on empiric immunotherapy within 8 days of presentation without requiring brain biopsy, given characteristic MRI imaging. CSF analysis demonstrated the presence of anti-GABAAR antibodies in all 3 cases. Cases 1 and 3 also tested positive for anti-GABAAR antibodies in the serum (serum test was not performed in case 2). Cases 1 and 2 recovered to work full-time within 1 year. Case 3 reported occasional myoclonic-like movement. DISCUSSION: We highlight the importance of considering anti-GABAAR encephalitis in patients with seizures, multifocal nonenhancing brain lesions, and a history of aHSCT for MM. Awareness in recovered post-aHSCT patients with MM may be crucial because prompt recognition can avoid brain biopsy and delays in treatment. The rapid initiation of immunotherapy while awaiting autoantibody results will likely improve functional outcomes.

Adrenal Crisis Presenting as Recurrent Encephalopathy Mimicking Autoimmune, Infectious Encephalitis, and Common Variable Immune Deficiency: A Case Report.

INTRODUCTION: Adrenal crisis can present with life-threatening complications and mimic autoimmune or infectious encephalitis, and common variable immune deficiency (CVID). The literature regarding the neurological complications of adrenal crisis is limited and focuses on patients who present with hypotension and electrolyte abnormalities. CASE REPORT: A 30-year-old man presented 3 times to our hospital with encephalopathy, fever, and left sided weakness with a history of multiple autoimmune diseases and prior hospitalizations for encephalopathy. During his first 2 admissions, he was normotensive and without electrolyte abnormalities. Extensive workup for infectious, paraneoplastic, seizure, metabolic, toxic, and vascular etiologies, and autoimmune encephalitis was negative. His exam returned to baseline with empiric steroid treatment, and he was discharged. He re-presented 2 months later with encephalopathy for a third admission. During this subsequent presentation, he had hyponatremia, low serum osmolality, elevated urine sodium, undetectable morning cortisol, and 21-α hydroxylase autoantibodies. A diagnosis of autoimmune adrenal insufficiency was established, he was treated with physiological doses of hydrocortisone and fludrocortisone, and improved rapidly to near baseline function. He has remained relapse-free at 4-year follow up. During all admissions, he was also found to have low immunoglobulin G levels and met criteria for CVID; however, his immunoglobin levels recovered with steroid replacement. CONCLUSION: The reported patient demonstrated some of the neurological complications of adrenal crisis which can mimic other autoimmune conditions such as CVID. The neurologist should be aware that recurrent encephalopathy from adrenal insufficiency can occur regardless of hemodynamic or electrolyte changes on typical hospital metabolic panels.

Idiopathic chronic temporal lobe herniation with associated epilepsy.

Herniation of parahippocampal gyrus is usually caused by pressure differentials intracranially, and herniation without known risk factors is extremely rare. We describe a patient with a long history of seizures and a remote status epilepticus event. On magnetic resonance imaging, a presumed left temporal lobe tumor was observed. On neurosurgical consultation, the lesion was identified as a chronic mesial temporal lobe herniation. The patient lacked history that would suggest risk of cerebral herniation. Accurately identifying the patient's chronic temporal lobe herniation radiographically likely saved this patient from unnecessary surgery or biopsy and allowed the patient to receive appropriate conservative care.

Repeat radiation with bevacizumab and minocycline in bevacizumab-refractory high grade gliomas: a prospective phase 1 trial.

INTRODUCTION: There are no effective treatments for gliomas after progression on radiation, temozolomide, and bevacizumab. Microglia activation may be involved in radiation resistance and can be inhibited by the brain penetrating antibiotic minocycline. In this phase 1 trial, we examined the safety and effect on survival, symptom burden, and neurocognitive function of reirradiation, minocycline, and bevacizumab. METHODS: The trial used a 3 + 3 design for dose escalation followed by a ten person dose expansion. Patients received reirradiation with dosing based on radiation oncologist judgment, bevacizumab 10 mg/kg IV every two weeks, and oral minocycline twice a day. Symptom burden was measured using MDASI-BT. Neurocognitive function was measured using the COGSTATE battery. RESULTS: The maximum tolerated dose of minocycline was 400 mg twice a day with no unexpected toxicities. The PFS3 was 64.6%, and median overall survival was 6.4 months. Symptom burden and neurocognitive function did not decline in the interval between treatment completion and tumor progression. CONCLUSIONS: Minocycline 400 mg orally twice a day with bevacizumab and reirradiation is well tolerated by physician and patient reported outcomes in people with gliomas that progress on bevacizumab.

Neurosarcoidosis: Longitudinal experience in a single-center, academic healthcare system.

OBJECTIVE: To characterize patients with neurosarcoidosis within the University of Utah healthcare system, including demographics, clinical characteristics, treatment, and long-term outcomes. METHODS: We describe the clinical features and outcomes of patients with neurosarcoidosis within the University of Utah healthcare system (a large referral center for 10% of the continental United States by land mass). Patients were selected who met the following criteria: (1) at least one International Classification of Diseases Clinical Modification, 9th revision code 135 or International Classification of Diseases Clinical Modification, 10th revision code D86* (sarcoidosis) and (2) at least one outpatient visit with a University of Utah clinician in the Neurology Department within the University of Utah electronic health record. RESULTS: We identified 56 patients meeting the study criteria. Thirty-five patients (63%) were women, and most patients (84%) were white. Twelve patients (22%) met the criteria for definite neurosarcoidosis, 36 patients (64%) were diagnosed with probable neurosarcoidosis, and 8 patients (14%) were diagnosed with possible neurosarcoidosis. A total of 8 medications were used for the treatment of neurosarcoidosis. Prednisone was the first-line treatment in 51 patients (91%). Infliximab was the most effective therapy, with 87% of patients remaining stable or improving on infliximab. Treatment response for methotrexate and azathioprine was mixed, and mycophenolate mofetil and rituximab were the least effective treatments in this cohort. CONCLUSIONS: This is a comprehensive characterization of neurosarcoidosis within a single healthcare system at the University of Utah that reports long-term response to treatment and outcomes of patients with neurosarcoidosis. Our results suggest the use of infliximab as a first-line therapy for neurosarcoidosis.

Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema.

OBJECTIVE: Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP. METHODS: Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension. RESULTS: Reduced pituitary gland height was moderately sensitive for IIH WP (80%) but had low specificity (64%). Increased optic nerve sheath diameter was less sensitive (51%) and only moderately specific (83%). Flattening of the posterior globe was highly specific (97%) but had low sensitivity (57%). Transverse venous sinus stenosis was moderately sensitive for IIH WP (78%) but of undetermined specificity. A combination of any 3 of 4 MRI features was nearly 100% specific, while maintaining a sensitivity of 64%. Of patients with CH + EOP, 30% had 3 or more MRI features, suggesting IIH WOP in those patients. CONCLUSION: A combination of any 3 of 4 MRI features is highly specific for intracranial hypertension and suggests IIH WOP when present in patients with chronic headache and no papilledema.

Intraprocedural predictors of post-stent retriever thrombectomy subarachnoid hemorrhage in middle cerebral artery stroke.

BACKGROUND: Stent retriever thrombectomy (SRT) in acute thromboembolic stroke can result in post-thrombectomy subarachnoid hemorrhage (PTSAH). Intraprocedural findings associated with PTSAH are not well defined. OBJECTIVE: To identify angiographic findings and procedural factors during SRT that are associated with PTSAH. MATERIALS AND METHODS: This was a retrospective, observational cohort study of consecutive patients with middle cerebral artery (MCA) acute ischemic stroke treated with SRT. Inclusion criteria were: (1) age ≥18 years; (2) thromboembolic occlusion of the MCA; (3) at least one stent retriever pass beginning in an M2 branch; (4) postprocedural CT or MRI scan within 24 hours; (5) non-enhanced CT Alberta Stroke Program Early CT Score >5. Exclusion criteria included multi-territory stroke before SRT. RESULTS: Eighty-five patients were enrolled; eight patients had PTSAH (group 1) and 77 did not (group 2). Baseline demographic and clinical characteristics were comparable between the two groups. In group 1, a significantly greater proportion of patients had more than two stent retriever passes (62.5% vs 18.2%, P=0.01), a stent retriever positioned ≥2 cm along an M2 branch (100% vs 30.2%, P=0.002), and the presence of severe iatrogenic vasospasm before SRT pass (37.5% vs 5.2%, P=0.02). One patient with PTSAH and associated mass effect deteriorated clinically. CONCLUSIONS: An increased number of stent retriever passes, distal device positioning, and presence of severe vasospasm were associated with PTSAH. Neurological deterioration with PTSAH can occur.

Gliosarcoma: Neuroimaging and Immunohistochemical Findings.

BACKGROUND AND PURPOSE: Gliosarcoma (GSC) is an intra-axial lesion which often abuts a dural margin and is composed of glial and mesenchymal elements. This lesion is considered a variant of isocitrate dehydrogenase (IDH)-wild type glioblastoma (GBM). The purpose of this study is to evaluate the imaging and molecular features of GSC in a large patient cohort. METHODS: Pathology-proved GSC cases were collected from our quaternary care center spanning the last 16 years and IDH status was documented. Older GSC cases without prior immunohistochemical testing underwent tissue block staining to obtain IDH status. When available, p53, phosphate and tensin (PTEN), MIB-1, EGFR amplification, and MGMT methylation were recorded and imaging findings tabulated. Logistic regression analyses were performed to determine correlation of molecular markers and imaging characteristics. RESULTS: A total of 25 cases were identified (21 de novo, 4 post-treatment). All lesions contacted a dural, pial, or ependymal surface and were negative for an IDH R132H mutation, including postradiation GSC. In total, 16 of 16 cases showed nonamplification of EGFR/CEP7, 2 of 16 demonstrated MGMT methylation, and multiple lesions demonstrated p53 and PTEN mutations. Imaging features included areas of nodular thickening in necrotic lesions which appeared to abut the site of dural contact. There was no significant correlation of molecular markers with imaging characteristics. CONCLUSION: GSC was IDH(-) in all cases, supporting the current understanding of this lesion being a wild-type GBM variant. Additional molecular markers demonstrated no significant correlation with imaging findings in this cohort.

Preoperative and intraoperative perfusion magnetic resonance imaging in a RELA fusion-positive anaplastic ependymoma: A case report.

BACKGROUND: Ependymomas are rare neuroepithelial tumors thought to arise from radial glial precursor cells lining the walls of the ventricles and central canal of the brain and spinal cord, respectively. Histopathological classification, according to World Health Organization criteria, has only recently defined the RELA-fusion positive ependymoma. These tumors may account for 70% of supratentorial ependymomas in children and represent an aggressive entity distinct from other ependymomas. CASE DESCRIPTION: Here we present the case of a patient with RELA-fusion positive ependymoma of the frontal lobe in whom we used preoperative and intraoperative magnetic resonance (MR) perfusion imaging. In this first demonstrated intraoperative evaluation of MR perfusion in ependymoma, increased peripheral perfusion of the lesion in a ring-like manner with a discrete cutoff around the surgical margin correlated with intraoperative findings of a clear border between the tumor and brain, as well as pathological findings of increased MIB index and hypercellularity-specifically within solid tumor components. An abnormal perfusion pattern also suggested an aggressive lesion, which was later confirmed on pathological analysis. In addition, intraoperative MR perfusion improved detection of tumor tissue in combination with traditional T1-weighted contrast-enhanced methods, which increased extent of resection. CONCLUSIONS: MR perfusion imaging may be a useful method for delineating tumor aggressiveness and borders, which can be prognostic.

Diffusion-Weighted Imaging and Post-contrast Enhancement in Differentiating Optic Neuritis and Non-arteritic Anterior Optic Neuropathy.

Non-arteritic anterior ischaemic optic neuropathy (NAION) and optic neuritis (ON) may be difficult to distinguish early in their disease courses. Our goal was to determine if specific magnetic resonance imaging characteristics differentiate acute NAION from ON. Neuroradiologists, masked to diagnosis, reviewed the diffusion-weighted imaging (DWI) and post-contrast enhancement (PCE) characteristics of the optic nerve in 140 eyes. PCE and DWI signals of the optic disc alone did not discriminate between NAION and ON. After taking age and sex into consideration, only DWI and PCE of the intraorbital segment of the optic nerve differentiated the two, with ON having the increased likelihood of these findings. Isolated PCE without DWI signal at the optic disc, however, was 100% specific for NAION. This may be the most specific way to radiographically differentiate between NAION and ON in the acute setting.

Leptomeningeal dissemination of a low-grade lumbar paraganglioma: case report.

Leptomeningeal dissemination of paraganglioma is rare, with only 2 prior cases in the literature. The authors present the case of a metastatic low-grade lumbar paraganglioma via leptomeningeal dissemination. This report emphasizes the utility of 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA) PET scanning for diagnosis, as well as the combination of radiation therapy and alkylating chemotherapeutic agents for the treatment of this rare phenomenon. The patient was a 61-year-old woman who presented with low-back pain and was found to have an isolated L-3 intrathecal tumor on MRI. Sixteen months after gross-total en bloc resection of the paraganglioma, the patient again became symptomatic with new neurological symptoms. MRI findings revealed enhancing leptomeningeal nodules throughout the spine. 18F-FDOPA PET/CT scanning was used to confirm the diagnosis of disseminated paraganglioma. Intrathecal thiotepa, radiation therapy, and systemic therapy with capecitabine and temozolomide have been used sequentially over a 2-year period, with each able to stabilize tumor growth for several months. The authors also summarize the 2 other reports of leptomeningeal dissemination of paragangliomas in the literature and compare the course and management of the 3 cases.

Surgical Treatment of Vestibular Schwannoma: Does Age Matter?

OBJECTIVE: For older patients (>65 years) who undergo surgical treatment of vestibular schwannoma (VS), the reported rates of facial nerve preservation, hearing preservation, and complications are inconsistent. Many surgeons believe that older patients have worse outcomes than their younger counterparts and advise against surgical treatment. We analyzed a consecutive series of patients with VS treated with surgery to determine whether age was a factor in outcome. METHODS: We retrospectively reviewed all patients treated for VS at our institution from January 1, 2000, to July 1, 2012. We examined how sex, age (≥65 years and <65 years), race, tumor size, tumor laterality, body mass index, Charlson Comorbidity Index, smoking status, surgical approach, and preoperative hearing and symptoms were associated with outcomes. RESULTS: Two-hundred forty-three patients underwent resection of VS, including 23 patients ≥65 years (mean 68 ± 4 years) and 220 patients <65 years (mean 47 ± 11 years). The average tumor size was 16.5 mm. Older patients had a significantly lower body mass index of 26.6 vs. 29.8 (P = 0.03) and were more likely to have a CCI ≥2 (52.2% vs. 18.2%, P ≤ 0.00, preoperative facial numbness (34.8% vs. 10.1%, P = 0.03), and dizziness (78.3% vs. 49.3%, P = 0.03). There were no significant differences after surgery in facial nerve outcome, hearing preservation outcome, or general surgical complications between the 2 cohorts. CONCLUSIONS: With no difference in surgical complications, facial nerve outcome, or hearing preservation rates between older and younger patients in our series, age alone may not be an absolute contraindication to surgical management of VS.

Spinal Neuroarthropathy: Pathophysiology, Clinical and Imaging Features, and Differential Diagnosis.

Spinal neuroarthropathy (SNA), or Charcot spine, is a progressive destructive arthropathy occurring after loss of neuroprotective sensation and proprioceptive reflexes. Clinical diagnosis is difficult because of the variable length to presentation after initial neurologic damage and the limited symptoms given preexisting neurologic deficits. SNA is also a diagnostic challenge because its imaging features are similar to those of spinal conditions such as discitis-osteomyelitis, osseous tuberculosis, hemodialysis-related spondyloarthropathy, and pseudarthrosis. The most important imaging clues for diagnosis of SNA are involvement of both anterior and posterior elements at the thoracolumbar and lumbosacral junctions. Additional imaging clues include vacuum phenomenon within the disk (indicating excessive motion), malalignment, and paraspinal soft-tissue masses or fluid collections containing bone debris. Despite these imaging signs, findings may overlap in some cases with those of infection, or SNA can be superinfected, and biopsy may be necessary. Development of SNA requires a preexisting neurologic condition, most commonly traumatic spinal cord injury. Areas of greatest mobility and weight bearing within the desensate spine experience repetitive microtrauma and unregulated hyperemia, leading to destruction of the intervertebral articulations. The progressive and destructive nature of SNA causes substantial deformity, loss of function, and often further neurologic deficits. Patients present with deformity, back pain, audible noises during movement, or new neurologic symptoms. The mainstay of treatment is surgical débridement, reduction, and fusion. The radiologist can help initiate early intervention by using key imaging features to distinguish SNA from imaging mimics and prevent further neurologic deterioration. (©)RSNA, 2016.

An unusual and challenging case of HIV-associated primary CNS Lymphoma with Hodgkin-like morphology and HIV encephalitis.

HIV-associated primary CNS lymphomas are well-recognized, almost exclusively EBV-driven neoplasms with poor clinical prognosis. We report a challenging, atypical case of an HIV-associated lymphoproliferative disorder with unusual morphologic features reminiscent of Hodgkin Lymphoma, accompanied by HIV encephalitis. A 52-year-old male presented with acute seizures after seven months of progressive neurocognitive decline that was clinically diagnosed as progressive supranuclear palsy. Clinical work-up revealed HIV infection along with two ring-enhancing lesions in the brain on MRI, and negative CSF EBV testing. Subsequent biopsy showed well-demarcated hypercellular regions in the brain comprised of scattered Reed-Sternberg-like cells in a background of small to medium-sized lymphocytes exhibiting focal angiocentricity and geographic necrosis. The atypical cells were positive for CD20, EBV, and CD79a, and negative for CD45, GFAP, CD15, CD30, and p24. These cells were admixed with numerous CD68-positive cells. The adjacent brain showed classic features of HIV encephalitis with perivascular, CD68 and p24-positive multinucleated giant cells. This case illustrates several diagnostic pitfalls in the work-up of HIV-associated brain lesions, as well as reporting a unique histomorphology for an HIV-related primary CNS lymphoproliferative disorder.

Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas.

The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors. Use of magnetic resonance spectroscopy can provide preoperative detection of IDH-mutated gliomas and affect surgical planning. In addition, IDH1 and IDH2 mutation status may have an effect on surgical resectability of gliomas. The IDH-mutated tumors exhibit better prognosis throughout every grade of glioma, and mutation may be an early genetic event, preceding lineage-specific secondary and tertiary alterations that transform LGGs into secondary glioblastomas. The O6-methylguanine-DNAmethyltransferase (MGMT) promoter methylation and 1p19q codeletion status can predict sensitivity to chemotherapy and radiation in low- and intermediate-grade gliomas. Thus, these recent advances, which have led to a better understanding of how molecular, genetic, and epigenetic alterations influence the pathogenicity of the different histological grades of gliomas, can lead to better prognostication and may lead to specific targeted surgical interventions and medical therapies.

Comparison of ferromagnetic induction and bipolar electrosurgery and suction in corticotomies in pig cerebrum.

INTRODUCTION: The effects of newer energy-based surgical dissection and coagulation modalities on cerebral tissue have not been investigated. Several instruments have been developed to address the limitations of traditional electrosurgical instruments in the nervous system. We compared the effects of standard bipolar electrocautery and suction (BPS) with those of a new ferromagnetic induction (FMI) device in corticotomies of pig cerebral tissue as assessed by magnetic resonance imaging (MRI) and histological analysis. METHODS: Three adult pigs underwent bilateral corticotomies (3 cm long×1 cm deep) using both FMI and BPS. The acute cerebral tissue edema created by each method was measured on coronal volumetric T2-weighted MRI sequences immediately after surgery. A lateral thermal "damage index" was calculated by dividing the width of the visible T2 tissue edema by the measured depth. The radiographic damage indices with each method were compared statistically. Histological analysis of each incision was conducted to compare the extent of tissue damage. RESULTS: MRI showed that the mean radiographic damage index of each corticotomy was significantly lower with the FMI (0.30 ± 0.02 (0.28-0.32)) than with the BPS method (0.54 ± 0.11 (0.42-0.64)) (p = 0.02). Histological analysis suggested a correlation with the radiographic findings as the FMI tissue samples demonstrated less adjacent tissue damage than BPS. CONCLUSIONS: FMI appeared to cause less adjacent tissue damage than the BPS method in pig cerebral tissue based on quantitative radiographic and qualitative histological analysis. Future studies are needed to investigate the clinical implications of energy-based surgical dissection on cerebral tissue.

Pineal region masses--imaging findings and surgical approaches.

The anatomy of the pineal region is complex. Despite advances in surgical techniques since the first reported successful pineal region surgery in the early 20th century, pineal region surgery remains challenging owing to the proximity of deep cerebral veins and dorsal midbrain structures critical for vision. In this article, we review the relevant surgical anatomy of the pineal region and discuss historically important and current surgical approaches. We describe specific imaging features of pineal region masses that may affect surgical planning and review neoplastic and nonneoplastic masses that occur in the pineal region.