Faculty Bibliography

BACKGROUND AND IMPORTANCE: Mucinous eccrine carcinoma (MEC) is a rare but distinct type of sweat gland tumor. MECs tend to recur locally, and their spread to distant organs is very uncommon. This article describes the first case of MEC metastasizing to the brain and the spine. CLINICAL PRESENTATION: A 45-year-old female presented with a 2-year history of a scalp mass in the occipital area with lymph node spread. She underwent excision of the mass and neck lymph node dissection. Pathology confirmed the diagnosis of MEC. Postoperatively, she received radiation to the involved areas. Four years later the patient presented with left hemiparesis and underwent craniotomy for gross total resection of the metastasis. This recurred after 2.5 years and she underwent another craniotomy for gross total resection followed by whole brain radiation. In addition, the patient had metastases to T11 vertebral body and the left C6 to 7 neural foramen. Moreover, the patient developed leptomeningeal disease in the spine. The metastases to the spine were treated with radiation therapy. The patient died 1.5 years later. CONCLUSION: Even though it is rare for MEC to spread to distant organs, physicians should be aware of the risk of metastatic invasion of the brain and spine and be vigilant about surveillance of these sites. MEC metastases to the brain should be treated aggressively with surgical resection followed by stereotactic radiosurgery to the tumor bed. Spine metastases should be treated with a combination of surgery and image-guided radiation therapy, depending on the degree of cord compression from epidural metastatic disease

OBJECTIVE: Medically refractory epilepsy is amenable to neurosurgical intervention if the epileptogenic focus is accurately localized. If the scalp video-electroencephalography (EEG) and magnetic resonance imaging are nonlateralizing, yet a single focus is suspected, video-EEG monitoring with bilateral intracranial electrode placement is helpful to lateralize the ictal onset zone. We describe the indications, risks, and utility of such bilateral surveys at our institution. METHODS: We retrospectively reviewed 26 patients with medically refractory seizures who were treated over a 5-year period and underwent bilateral placement of intracranial electrodes. Subdural strips were used in all cases, and additional stereotactic implantation of depth electrodes into mesial temporal lobes occurred in 50%. The mean patient age was 37.7 years, and 65.4% of patients were male. RESULTS: The most common indication for bilateral invasive monitoring was bilateral ictal onsets on surface video-EEG (76.9%), followed by frequent interictal spikes contralateral to a single ictal focus (7.7%). Intracranial monitoring lasted an average of 8.2 days, with ictal events recorded in all cases. Ten patients (38.5%) subsequently underwent more extensive unilateral monitoring via implantation of subdural and depth electrodes through a craniotomy. A therapeutic procedure was performed in 17 patients (65.4%), whereas 1 patient underwent a palliative corpus callosotomy (3.8%). Nine patients underwent a resection without unilateral invasive mapping. Reasons for no therapeutic surgery (n = 8) included multifocal onsets, failing the Wada test, refusal of further treatment, and negative intraoperative electrocorticogram. There was 1 surgical complication, involving a retained electrode fragment that was removed in a separate minor procedure. Of the 26 patients, 15 (57.7%) are now seizure-free or have seizure disorders that have substantially improved (modified Engel classes I and II). Of the 17 patients who underwent a potentially curative surgery, 13 (76.5%) were Engel classes I and II. CONCLUSION: Bilateral placement of subdural strip and depth electrodes for epilepsy monitoring in patients with nonlateralizing scalp EEG and/or discordant imaging studies but clinical suspicion for focal seizure origin is both safe and effective. Given the safety and efficacy of this procedure, epileptologists should have a low threshold to consider bilateral implants for suitable patients

Pharmacologic therapy represents the first line of treatment of epilepsy and is effective in most patients. However, about 20% to 30% of cases develop intractable seizures that cannot be controlled by medication alone. In such cases, surgical intervention is considered for therapeutic, often curative purposes. Dynamic spatiotemporal variability in the epileptic focus renders seizure localization a challenge to the clinician. Many diagnostic modalities have been developed to identify different aspects of the epileptic focus. Older techniques are being increasingly supplemented by a variety of anatomic and functional imaging modalities that can help clarify discrepancies. Invasive electroencephalography remains the gold standard for identifying epileptic foci and guiding the surgeon to successful resections

Human embryonic stem cells (hESCs) have enormous potential for applications in basic biology and regenerative medicine. However, harnessing the potential of hESCs toward generating homogeneous populations of specialized cells remains challenging. Here we describe a novel technology for the genetic identification of defined hESC-derived neural cell types using bacterial artificial chromosome (BAC) transgenesis. We generated hESC lines stably expressing Hes5::GFP, Dll1::GFP, and HB9::GFP BACs that yield green fluorescent protein (GFP)(+) neural stem cells, neuroblasts, and motor neurons, respectively. Faithful reporter expression was confirmed by cell fate analysis and appropriate transgene regulation. Prospective isolation of HB9::GFP(+) cells yielded purified human motor neurons with proper marker expression and electrophysiological activity. Global mRNA and microRNA analyses of Hes5::GFP(+) and HB9::GFP(+) populations revealed highly specific expression signatures, suggesting that BAC transgenesis will be a powerful tool for establishing expression libraries that define the human neural lineage and for accessing defined cell types in applications of human disease

OBJECT: In this retrospective analysis the authors describe the assessment and outcomes of 90 patients who underwent placement of posterior instrumentation at the cervicothoracic junction following the resection of a primary or metastatic tumor during a 10-year period. METHODS: All patients underwent a posterolateral laminectomy including uni- or bilateral facetectomy, and 44 patients additionally required vertebral body resection and reconstruction. In patients who underwent C-6 or C-7 decompression, the posterior instrumentation strategies changed from the use of lateral mass plate systems (LMPSs) to lateral mass screw/rod systems (LMSRSs). Similarly, for T1-3 tumor decompression, the strategy shifted from sublaminar hook/rod systems (SHRSs) to the use of pedicle screw systems (PSSs) in which the surgeon used either a 6.25-mm rod or dual-diameter rods with or without a connector. RESULTS: The overall surgical complication rate was 19% including fixation failure in 11 patients (12%), 6 of whom required reoperation. Fixation failure rates for cervical decompression decreased from 2 (29%) of 7 patients in the LMPS group to 0 (0%) of 8 in the LMSRS group (p = 0.2). The fixation failure rates for thoracic decompression were 7 (15%) of 48 patients in the SHRS group, and there was a decrease to 2 (7%) of 27 in the PSS group (p = 0.48). Neurological and functional outcomes including American Spinal Injury Association, Eastern Cooperative Oncology Group, and Medical Research Council muscle strength and pain scores remained stable or improved in 94, 96, 100, and 96% of patients, respectively. CONCLUSIONS: Current posterior instrumentation strategies involving LMSRSs and PSSs provide excellent and safe stabilization of the cervicothoracic junction following resection of primary or metastatic tumors

High-throughput screening (HTS) of chemical libraries has become a critical tool in basic biology and drug discovery. However, its implementation and the adaptation of high-content assays to human embryonic stem cells (hESCs) have been hampered by multiple technical challenges. Here we present a strategy to adapt hESCs to HTS conditions, resulting in an assay suitable for the discovery of small molecules that drive hESC self-renewal or differentiation. Use of this new assay has led to the identification of several marketed drugs and natural compounds promoting short-term hESC maintenance and compounds directing early lineage choice during differentiation. Global gene expression analysis upon drug treatment defines known and novel pathways correlated to hESC self-renewal and differentiation. Our results demonstrate feasibility of hESC-based HTS and enhance the repertoire of chemical compounds for manipulating hESC fate. The availability of high-content assays should accelerate progress in basic and translational hESC biology

OBJECTIVE: Intraoperative identification of cerebrospinal fluid (CSF) leakage is critical in successful closure after endoscopic cranial base surgery. Intrathecal injection of fluorescein is quite useful in identifying CSF leaks. However, complications have been reported with various doses and the technique has fallen out of favor. We explored the safety of low-dose intrathecal fluorescein administered to patients undergoing endoscopic cranial base surgery. METHODS: A retrospective chart review and postoperative patient survey were performed. The nature and incidence of complications and subjective complaints were recorded in 54 patients who underwent endoscopic, endonasal approaches to the anterior cranial base and received intrathecal fluorescein after premedication with dexamethasone and diphenhydramine. RESULTS: Intraoperative CSF leak was identified with fluorescein in 46.3% of the patients and helped determine the reconstruction technique. Postoperative CSF leak occurred in 9.3% of the patients and resolved with lumbar drainage. There were no seizures. Most side effects were nonspecific, transient, and likely not caused by fluorescein including malaise (57.4%), headache (51.9%), dizziness (31.5%), or nausea/vomiting (24.1%). Three patients (5.6%) experienced persistent subjective lower extremity weakness (n = 2) and numbness (n = 2) postoperatively; however, two of them had undergone lumbar drainage. CONCLUSION: Low-dose injection of intrathecal fluorescein after premedication with steroid and antihistamine agents is generally safe. Most symptoms are nonspecific and transient, likely caused by the surgery or lumbar drainage. However, fluorescein should be administered with some caution because it may be responsible for occasional lower extremity weakness and numbness

OBJECTIVES: Reconstruction following endoscopic skull base surgery requires a high degree of success to avoid the morbidity of postoperative cerebrospinal fluid (CSF) leak. The impact on outcomes of CSF visualization with intrathecal fluorescein, however, is unknown. STUDY DESIGN: A retrospective review of patients undergoing endoscopic skull base surgery with intrathecal fluorescein. A possible correlation between intraoperative fluorescein identification and postoperative CSF leak was analyzed. RESULTS: 61 patients underwent surgery for a variety of lesions including pituitary adenoma (55.7%), encephalocele (14.8%), and meningioma (9.8%). Seven (19.4%) of the 37 patients with intraoperative fluorescein leak experienced postoperative CSF leak compared to 0 of the 24 patients who did not have intraoperative fluorescein leak (P = 0.02). All cases of CSF leak resolved with lumbar drainage alone. CONCLUSIONS: The lack of intraoperative fluorescein leakage correlates strongly with a low risk for postoperative CSF leak. This can be used to stratify the extent of skull base reconstruction required during endoscopic skull base surgeries