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OBJECTIVEAdvanced microsurgical techniques contribute to reduced morbidity and improved surgical management of meningiomas arising within the cerebellopontine angle (CPA). However, the goal of surgery has evolved to preserve the quality of the patient's life, even if it means leaving residual tumor. Concurrently, Gamma Knife radiosurgery (GKRS) has become an acceptable and effective treatment modality for newly diagnosed, recurrent, or progressive meningiomas of the CPA. The authors review their institutional experience with CPA meningiomas treated with GKRS, surgery, or a combination of surgery and GKRS. They specifically focus on rates of facial nerve preservation and characterize specific anatomical features of tumor location with respect to the internal auditory canal (IAC).METHODSMedical records of 76 patients with radiographic evidence or a postoperative diagnosis of CPA meningioma, treated by a single surgeon between 1992 and 2016, were retrospectively reviewed. Patients with CPA meningiomas smaller than 2.5 cm in greatest dimension were treated with GKRS, while patients with tumors 2.5 cm or larger underwent facial nerve–sparing microsurgical resection where appropriate. Various patient, clinical, and tumor data were gathered. Anatomical features of the tumor origin as seen on preoperative imaging confirmed by intraoperative investigation were evaluated for prognostic significance. Facial nerve preservation rates were evaluated.RESULTSAccording to our treatment paradigm, 51 (67.1%) patients underwent microsurgical resection and 25 (32.9%) patients underwent GKRS. Gross-total resection (GTR) was achieved in 34 (66.7%) patients, and subtotal resection (STR) in 17 (33.3%) patients. Tumors recurred in 12 (23.5%) patients initially treated surgically, requiring additional surgery and/or GKRS. Facial nerve function was unchanged or improved in 68 (89.5%) patients. Worsening facial nerve function occurred in 8 (10.5%) patients, all of whom had undergone microsurgical resection. Upfront treatment with GKRS for CPA meningiomas smaller than 2.5 cm was associated with preservation of facial nerve function in all patients over a median follow-up of 46 months, regardless of IAC invasion and tumor origin. Anatomical origin was associated with extent of resection but did not correlate with postoperative facial nerve function. Tumor size, extent of resection, and the presence of an arachnoid plane separating the tumor and the contents of the IAC were associated with postoperative facial nerve outcomes.CONCLUSIONSCPA meningiomas remain challenging lesions to treat, given their proximity to critical neurovascular structures. GKRS is a safe and effective option for managing CPA meningiomas smaller than 2.5 cm without associated mass effect or acute neurological symptoms. Maximal safe resection with preservation of neurological function can be performed for tumors 2.5 cm or larger without significant risk of facial nerve dysfunction, and, when combined with GKRS for recurrence and/or progression, provides excellent disease control. Anatomical features of the tumor origin offer critical insights for optimizing facial nerve preservation in this cohort.

Objective Subependymomas are infrequent, low-grade gliomas associated with the ventricular system and the spinal cord. Little is known about the origin and natural history of these slow-growing lesions. Methods We identified all patients with pathologically proven subependymomas presenting to our institution between 1998 and 2016. We retrospectively reviewed clinical, radiographic, histologic, and surgical outcomes data in all patients who underwent surgical resection. Immunohistochemical analyses for cell lineage markers were performed. Results A total of 31 patients with pathologically proven subependymomas were identified. Of these, 7 asymptomatic lesions were discovered at autopsy and 24 symptomatic cases were treated surgically. There were 15 (48%) lateral ventricle tumors, 11 (35%) fourth ventricular tumors, and 5 (17%) spinal tumors. Symptomatic intracranial lesions most commonly presented with headaches and balance and gait abnormalities. Subependymomas had no distinguishing radiographic features that provided definitive preoperative diagnosis. At last follow-up, no patient treated surgically experienced recurrence. Immunohistochemical analyses demonstrated a diffusely GFAP-positive glial neoplasm with mixed populations of cells that were variably positive for Olig2, NHERF1, Sox2, and CD44. The Ki67 proliferation index was generally low ( Conclusions Subependymomas demonstrate mixed populations of cells expressing glial lineage markers as well as putative stem cell markers, suggesting these tumors may arise from multipotent glial progenitors that reside in the subventricular zone. Definitive diagnosis requires surgical sampling. Although the clinical course of subependymomas appears benign, the inability to radiographically diagnose these lesions, and the possibility of an alternative malignant lesion support a low threshold for early and safe maximal resection.

We present a patient with prednisone-induced spinal epidural lipomatosis (SEL) and relatively acute neurologic deterioration followed by rapid recovery after surgical decompression. SEL is a rare disease characterized by hypertrophy of epidural fat, most commonly associated with exogenous steroid use. To our knowledge, an analysis of the dynamics of steroid dose related to time to onset has never been performed, or of patient presentation features with respect to patient outcome. We retrospectively reviewed the literature for English language series and case reports of SEL associated with prednisone use from 1975-2013. Data were compiled for 41 patients regarding the prescribed dose of prednisone and length of treatment, as well as the severity of symptoms on the Ranawat scale, time to onset, time to recovery, and degree of recovery of neurological symptoms. Fisher's exact test and analysis of variance were used for comparing proportions, and p values

Low-frequency depression (LFD) of transmitter release occurs at phasic synapses with stimulation at 0.2 Hz in both isolated crayfish (Procambarus clarkii) neuromuscular junction (NMJ) preparations and in intact animals. LFD is regulated by presynaptic activity of the Ca2+-dependent phosphatase calcineurin (Silverman-Gavrila and Charlton, 2009). Since the fast Ca2+chelator BAPTA-AM inhibits LFD but the slow chelator EGTA-AM does not, the Ca2+sensor for LFD may be close to a Ca2+source at active zones. Calcineurin can be activated by the Ca2+-activated protease calpain, and immunostaining showed that both proteins are present at nerve terminals. Three calpain inhibitors, calpain inhibitor I, MDL-28170, and PD150606, but not the control compound PD145305, inhibit LFD both in the intact animal as shown by electromyograms and by intracellular recordings at neuromuscular junctions. Analysis of mini-EPSPs indicated that these inhibitors had minimal postsynaptic effects. Proteolytic activity in CNS extract, detected by a fluorescent calpain substrate, was modulated by Ca2+and calpain inhibitors. Western blot analysis of CNS extract showed that proteolysis of calcineurin to a fragment consistent with the constitutively active form required Ca2+and was blocked by calpain inhibitors. Inhibition of LFD by calpain inhibition blocks the reduction in phosphoactin and the depolymerization of tubulin that normally occurs in LFD, probably by blocking the dephosphorylation of cytoskeletal proteins by calcineurin. In contrast, high-frequency depression does not involve protein phosphorylation- or calpain-dependent mechanisms. LFD may involve a specific pathway in which local Ca2+signaling activates presynaptic calpain and calcineurin at active zones and causes changes of tubulin cytoskeleton.

BACKGROUND: Pineal region tumors are rare and diverse. Among them exist reports of pleomorphic xanthroastrocytoma (PXA) and pleomorphic granular cell astrocytoma (PGCA) of the pineal gland. These related tumors are remarkably similar sharing pleomorphic histologic features with only minor immunohistochemical and ultrastructural differences. CASE DESCRIPTION: We present a case of a 42-year old right-handed woman presented with a longstanding history of migraine headaches which had worsened over the two months leading up to her hospitalization. MRI revealed a 1.7 × 1.3 × 1.6 cm intensely enhancing lesion originating in the pineal gland. The tumor closely resembled PGCA but did not strictly fit the diagnostic requirements of either PGCA or PXA. CONCLUSION: The present case highlights the exotic nature of pineal region tumors with pleomorphic cell histology. Given the diverse range of tumors encountered in the pineal region, pathological confirmation is mandatory. Favorable clinical outcomes demonstrate that surgical resection alone can yield excellent long-term results for tumors falling within the spectrum of pleomorphic lesions of the pineal gland.

Topoisomerase II (TOP2) is highly expressed on proneural gliomas, but its specific function on these tumors is unknown. We found that TOP2 is expressed in gliomas from early stages, increases during progression, and is elevated in radiographically localized non-enhancing regions of human glioblastoma, an area that is challenging to target systemically, and a common source of recurrence. TOP2A is highly expressed by infiltrating tumor cells, in the tumor center and at the edges, and low on surrounding brain. TOP2 enzymatic activity was detected on proneural glioma cell lines. TOP2 poison etoposide and 3 TOP2 inhibitors showed significant cytotoxicity on a proneural glioma cells (IC50 0.3-4 mM). Moreover, intracranial etoposide convection-enhanced delivery (CED) (80 mM) was tolerated and led to a significant survival benefit in mouse proneural gliomas. In contrast, etoposide CED (4 mM) showed transient decrease in tumor growth but failed to prolong survival, consistent with ineffective tumoral concentrations in trials of systemic etoposide for recurrent gliomas. TOP2 transcriptional modulation on proneural gliomas was suggested as the activity of many key transcription factors correlates with TOP2 levels across glioblastoma patients. TOP2 pharmacological targeting is a promising treatment target for some gliomas. Refining patient selection and drug delivery is key for optimizing this therapy.

OBJECTIVE: Subependymomas are infrequent, low-grade gliomas associated with the ventricular system and the spinal cord. Little is known about the origin and natural history of these slow-growing lesions. METHODS: We identified all patients with pathologically proven subependymomas presenting to our institution between 1998 and 2013. We retrospectively reviewed clinical, radiographic, histological, and surgical outcomes data in all patients who underwent surgical resection. Immunohistochemical analyses for a number of cell lineage markers was performed. RESULTS: A total of 24 patients with pathologically proven subependymomas were identified. Of these, 7 asymptomatic lesions were discovered at autopsy and 17 symptomatic cases were treated surgically. There were 8 lateral ventricle tumors, 5 spinal tumors and 4 fourth ventricular tumors. Symptomatic intracranial lesions most commonly presented with headaches, changes in vision, and balance difficulty. Subependymomas had no distinguishing radiographic features that provided definitive pre-operative diagnosis. At last follow up, no patient treated surgically experienced recurrence, although one patient with histologically mixed subependymoma-ependymoma subsequently developed and was treated for a remote glioblastoma. Immunohistochemical analyses demonstrated mixed populations of cells that were variably positive for Olig2, NeuN, Sox2, and CD44. CONCLUSION: Subependymomas demonstrate a mixed population of cells expressing neuronal and glial lineage markers as well as putative stem cell markers, suggesting these tumors may arise from multipotential progenitors that reside in the subventricular zone. Definitive diagnosis requires surgical sampling. While the clinical course is usually benign following surgical resection, the rare association with glial malignancy and the potential for malignant progression merits further investigation.