Flexible, scalable, high channel count stereo-electrode for recording in the human brain.

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on an innovative, customizable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents an advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology.

Superior Efficacy of Gross Total Resection in Anaplastic Astrocytoma Patients Relative to Glioblastoma Patients.

INTRODUCTION: Because of their relative rarity, anaplastic astrocytomas (AAs) often are grouped with glioblastomas in clinical treatment paradigms. There are reasons, however, to expect that the therapeutic response of AAs may differ from those of glioblastoma. Here, we examined the clinical benefit of gross total resection (GTR) in AA relative to glioblastoma patients. METHODS: Using the Surveillance, Epidemiology and End Results database, we identified 2755 patients with AA and patients with 21,962 glioblastoma between 1999 and 2010. Surgical resection was defined as GTR, subtotal resection (STR), biopsy only, or no resection. Kaplan-Meier curves and multivariate Cox regression were used to assess the association between GTR and survival. RESULTS: The hazard of dying from the AA was reduced in GTR patients by 40% relative to STR patients. This reduction is 59% greater than that observed in glioblastoma where GTR was associated only with a 24% reduction relative to STR (P < 0.0001). The median survival for patients with AA who underwent GTR and subtotal resection were 64 and 24 months, respectively. For glioblastoma patients, the corresponding numbers for median survival were 13 and 9 months, respectively. The survival benefit of GTR in patients with AA was particularly notable in patient age < 50, where the median survival was not reached during the study period. CONCLUSIONS: The Surveillance, Epidemiology and End Results data suggest that survival benefit associated with GTR was greater for patients with AA relative to glioblastoma patients, particularly for patients < age 50.

The role of the epidermal growth factor receptor in human gliomas: I. The control of cell growth.

The epidermal growth factor receptor (EGFR) gene is amplified in over 40% of primary human glioblastomas and overexpressed in the majority. The authors' investigations demonstrate that the function of the EGFR in glioblastomas is distinct from that in other human cancers because it does not appear to mediate the primary growth-promoting effect of EGF. Findings show that the level of EGFR expression does not directly predict the growth response to EGF, with growth stimulated in some cells but inhibited in others when cells were cultured in plastic dishes. On the other hand, when human glioblastoma cells were placed in soft agar cultures, the cell line expressing the highest levels of the EGFR demonstrated considerable colony formation in response to EGF treatment. In addition, cell lines with the highest EGFR levels were also more resistant to the growth-suppressive effects of retinoic acid when maintained in soft agar. These observations suggest that even though the overexpression of the EGFR did not confer a distinct growth advantage to glioma cells cultured on flat culture dishes, the ability of these cells to maintain anchorage-independent growth in soft agar especially in response to EGF and retinoic acid is facilitated. Because anchorage-independent growth is the best in vitro correlate to tumorigenicity, amplification and overexpression of the EGFR in human glioblastoma cells may be in part responsible for the tumorigenic potential of these cells.

The role of the epidermal growth factor receptor in human gliomas: II. The control of glial process extension and the expression of glial fibrillary acidic protein.

Our earlier investigations of the biology of the epidermal growth factor receptor (EGFR) in human gliomas demonstrated that the level of EGFR expression did not directly predict the glioma growth response to EGF, suggesting that the function of the EGFR in glioblastomas might not be limited to mediating the growth effects of EGF. We conducted the current studies to investigate the function(s) of the EGFR not related to growth control in human gliomas. These investigations show that the EGFR mediates the stimulative effects of EGF on glial process extension and glial fibrillary acidic protein (GFAP) expression. In addition, the level of EGFR expression correlates inversely with glioma cell responsiveness to differentiation promoting agents (for example, nerve growth factor and transforming growth factor-beta) that act through transmembrane tyrosine kinase receptors. Thus, glioma lines with a high level of EGFR expression (for example, T-98G cells) responded to fewer differentiation promoting factors than lines with a low level of EGFR expression (such as U-373MG cells). Our results suggest that the EGFR in gliomas may participate in mediating the process extension and GFAP stimulative effects of both EGF and other differentiation promoting agents. These properties represent components of the differentiated state in glia because their expression is stimulated by dibutyryl cyclic adenosine monophosphate in normal astrocytes. The involvement of the EGFR in the expression of these glial specific properties suggests that the EGFR may play an important role in glial differentiation.

Microsurgical treatment of intracranial vascular malformations.

In the period 1968 to 1978, 83 vascular malformations (AVM's) were treated by operation: 65 were excised and 18 were managed by interruption of afferent arteries. Three cryptic AVM's (two in the thalamus and one in the caudate nucleus) were discovered during exploration of hematomas in normotensive young women. All three of these small malformations were detected on computerized tomographic scans; none was apparent on preoperative angiograms. Two of the four deaths in this series occurred after excision of large, high-flow fistulas; the proposed cause was restoration of normal perfusion pressure in a chronically ischemic hemisphere rendered incapable of autoregulation. The addition of operative adjuncts, in particular, bipolar coagulation and operative microscopy, has extended traditional indications for operation to include favorably situated AVM's that have not bled and certain AVM's situated in critical regions of the brain.