Theodore H. Schwartz

Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain

Both late-gestation and adult human forebrain contain large numbers of oligodendrocyte progenitor cells (OPCs). These cells may be identified by their A2B5+PSA-NCAM− phenotype (positive for the early oligodendrocyte marker A2B5 and negative for the polysialylated neural cell adhesion molecule). We used dual-color fluorescence-activated cell sorting (FACS) to extract OPCs from 21- to 23-week-old fetal human forebrain, and A2B5 selection to extract these cells from adult white matter. When xenografted to the forebrains of newborn shiverer mice, fetal OPCs dispersed throughout the white matter and developed into oligodendrocytes and astrocytes. By 12 weeks, the host brains showed extensive myelin production, compaction and axonal myelination. Isolates of OPCs derived from adult human white matter also myelinated shiverer mouse brain, but much more rapidly than their fetal counterparts, achieving widespread and dense myelin basic protein (MBP) expression by 4 weeks after grafting. Adult OPCs generated oligodendrocytes more efficiently than fetal OPCs, and ensheathed more host axons per donor cell than fetal cells. Both fetal and adult OPC phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets.

Endoscopic pituitary surgery: a systematic review and meta-analysis

OBJECT Surgery on the pituitary gland is increasingly being performed through an endoscopic approach. However, there is little published data on its safety and relative advantages over traditional microscope-based approaches. Published reports are limited by small sample size and nonrandomized study design. A meta-analysis allows for a description of the impact of endoscopic surgery on short-term outcomes. METHODS The authors performed retrospective review of data from their institution as well as a systematic review of the literature. The pooled data were analyzed for descriptive statistics on short-term outcomes. RESULTS Nine studies (821 patients) met inclusion criteria. Overall, the pooled rate of gross tumor removal was 78% (95% CI 67-89%). Hormone resolution was achieved in 81% (95% CI 71-91%) of adrenocorticotropic hormone secreting tumors, 84% (95% CI 76-92%) of growth hormone secreting tumors, and 82% (95% CI 70-94%) of prolactin secreting tumors. The pooled complication rates were 2% (95% CI 0-4%) for CSF leak and 1% (95% CI 0-2%) for permanent diabetes insipidus. There were 2 deaths reported in the literature that were both related to vascular injury, giving an overall mortality rate of 0.24%. CONCLUSIONS The results of this meta-analysis support the safety and short-term efficacy of endoscopic pituitary surgery. Future studies with long-term follow-up are required to determine tumor control.

Endoscopic cranial base surgery: classification of operative approaches.

OBJECTIVE Endoscopic cranial base surgery is a minimal access, maximally aggressive alternative to traditional transfacial, transcranial, or combined open cranial base approaches. Previous descriptions of endoscopic approaches have used varying terminology, which can be confusing to the new practitioner. Indications for surgery are not well defined. Our objective was to create a comprehensive classification system of the various approaches and describe their indications with case examples. METHODS We prospectively compiled a comprehensive database of our endonasal endoscopic operations, detailing the nasal sinus transgressed, the cranial base approach, and the intracranial target for the first 150 consecutive cases performed at our institution. All cases were performed collaboratively by a neurosurgeon and an otolaryngologist. RESULTS We categorized the endonasal endoscopic cranial base operations into four nasal corridors, nine cranial base approaches, and 13 intracranial targets. Each of the various approaches is described in detail and illustrated with case examples. Pathology encountered included pituitary tumor (50%), meningocele/encephalocele (14%), craniopharyngioma and Rathke cleft cyst (10%), meningioma (8%), chordoma (5%), esthesioneuroblastoma (2%), and other (11%). CONCLUSION Endonasal endoscopic cranial base surgery is a minimal access, maximally invasive alternative to open transcranial cranial base approaches for specific indications. A clear understanding of the possible approaches is facilitated by an awareness of the nasal corridors and intracranial targets.

Perimesencephalic Nonaneurysmal Subarachnoid Hemorrhage: Review of the Literature

OBJECTIVE A critical review of the literature on the incidence, presentation, diagnosis, and prognosis of perimesencephalic nonaneurysmal subarachnoid hemorrhage. METHODS Review of the relevant literature. CONCLUSION The importance of early computed tomography (< 3 d), anatomy of the perimesencephalic and neighboring cisterns, and adequate four-vessel angiography are discussed. Treatment strategies, including the avoidance of repeated angiographic studies and surgical exploration, are presented.

“Gasket-seal” Watertight Closure in Minimal-access Endoscopic Cranial Base Surgery

OBJECTIVE Transnasal endoscopic cranial base surgery is a novel minimal-access method for reaching the midline cranial base. Postoperative cerebrospinal fluid leak remains a persistent challenge. A new method for watertight closure of the anterior cranial base is presented. METHODS To achieve watertight closure of the anterior cranial base, autologous fascia lata was used to create a “gasket seal” around a bone buttress, followed by application of a tissue sealant such as DuraSeal (Confluent Surgical, Inc., Waltham, MA). The gasket-seal closure was used to seal the anterior cranial base in a series of 10 patients with intradural surgery for suprasellar craniopharyngiomas (n = 5), planum meningiomas (n = 3), clival chordoma (n = 1), and recurrent iatrogenic cerebrospinal fluid leak (n = 1). Lumbar drains were placed intraoperatively in five patients and remained in place for 3 days postoperatively. RESULTS After a mean follow-up period of 12 months, there were no cerebrospinal fluid leaks. CONCLUSION The gasket-seal closure is an effective method for achieving watertight closure of the anterior cranial base after endoscopic intradural surgery.

Poor drug distribution as a possible explanation for the results of the PRECISE trial

OBJECT Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. METHODS Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. RESULTS Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. CONCLUSIONS The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

A human intracranial study of long-range oscillatory coherence across a frontal-occipital-hippocampal brain network during visual object processing.

Visual object-recognition is thought to involve activation of a distributed network of cortical regions, nodes of which include the lateral prefrontal cortex, the so-called lateral occipital complex (LOC), and the hippocampal formation. It has been proposed that long-range oscillatory synchronization is a major mode of coordinating such a distributed network. Here, intracranial recordings were made from three humans as they performed a challenging visual object-recognition task that required them to identify barely recognizable fragmented line-drawings of common objects. Subdural electrodes were placed over the prefrontal cortex and LOC, and depth electrodes were placed within the hippocampal formation. Robust beta-band coherence was evident in all subjects during processing of recognizable fragmented images. Significantly lower coherence was evident during processing of unrecognizable scrambled versions of the same. The results indicate that transient beta-band oscillatory coupling between these three distributed cortical regions may reflect a mechanism for effective communication during visual object processing.

Intramedullary Ependymomas: Clinical Presentation, Surgical Treatment Strategies and Prognosis

Intramedullary ependymomas are rare tumors but comprise the majority of intramedullary glial neoplasms in the adult. These tumors are benign, slow-growing lesions which are optimally treated with gross-total surgical resection without adjuvant therapy. This objective can be attained safely in a majority, of patients. Post-operative functional outcome is related to pre-operative functional status. Hence, early diagnosis, prior to symptomatic progression, is critical to the successful treatment of these tumors. Adjuvant therapy is indicated for the rare malignant or disseminated tumor or following sub-total resection.

Dexmedetomidine and neurocognitive testing in awake craniotomy.

Patients are selected for awake craniotomy when the planned procedure involves eloquent areas of the brain, necessitating an awake, cooperative patient capable of undergoing neurocognitive testing. Different anesthetic combinations, including neurolept, propofol with or without opioid infusions, and asleep-awake-asleep techniques, have been reported for awake craniotomy. In all these techniques, respiratory depression has been reported as a complication. In this case series dexmedetomidine, the highly selective alpha-2 adrenoreceptor agonist, was selected for its lack of respiratory depression as well as its sedative and analgesic properties. The charts of 10 consecutive patients who underwent awake craniotomy with dexmedetomidine infusion were reviewed. Five of the patients underwent “asleep-awake” technique with a laryngeal mask airway and volatile agent. Five patients received moderate to conscious sedation. All patients received a dexmedetomidine load of 0.5 to 1.0 &mgr;g/kg over 20 minutes followed by an infusion at rates of 0.01 to 1.0 &mgr;g/kg per hour. Four patients had extensive sensory and motor testing, and six underwent neurocognitive testing, including naming, reading, counting, and verbal fluency. There were no permanent neurologic deficits, except one patient who had an exacerbation of preoperative language difficulties. Dexmedetomidine appears to be a useful sedative for awake craniotomy when sophisticated neurologic testing is required.

Three-dimensional endoscopic pituitary surgery.

OBJECTIVE We describe a novel 3-dimensional (3-D) stereoendoscope and discuss our early experience using it to provide improved depth perception during transsphenoidal pituitary surgery. METHODS Thirteen patients underwent endonasal endoscopic transsphenoidal surgery. A 6.5-, 4.9-, or 4.0-mm, 0- and 30-degree rigid 3-D stereoendoscope (Visionsense, Ltd., Petach Tikva, Israel) was used in all cases. The endoscope is based on “compound eye” technology, incorporating a microarray of lenses. Patients were followed prospectively and compared with a matched group of patients who underwent endoscopic surgery with a 2-dimensional (2-D) endoscope. Surgeon comfort and/or complaints regarding the endoscope were recorded. RESULTS The 3-D endoscope was used as the sole method of visualization to remove 10 pituitary adenomas, 1 cystic xanthogranuloma, 1 metastasis, and 1 cavernous sinus hemangioma. Improved depth perception without eye strain or headache was noted by the surgeons. There were no intraoperative complications. All patients without cavernous sinus extension (7of 9 patients) had gross tumor removal. There were no significant differences in operative time, length of stay, or extent of resection compared with cases in which a 2-D endoscope was used. Subjective depth perception was improved compared with standard 2-D scopes. CONCLUSION In this first reported series of purely 3-D endoscopic transsphenoidal pituitary surgery, we demonstrate subjectively improved depth perception and excellent outcomes with no increase in operative time. Three-dimensional endoscopes may become the standard tool for minimal access neurosurgery.