Jonathan G. Thomas

Brain stimulation for the treatment of epilepsy.

The treatment of patients with refractory epilepsy has always been challenging. Despite the availability of multiple antiepileptic medications and surgical procedures with which to resect seizure foci, there is a subset of epilepsy patients for whom little can be done. Currently available treatment options for these unfortunate patients include vagus nerve stimulation, the ketogenic diet, and electric stimulation, both direct and indirect, of brain nuclei thought to be involved in epileptogenesis. Studies of electrical stimulation of the brain in epilepsy treatment date back to the early 20th century, beginning with research on cerebellar stimulation. The number of potential targets has increased over the years to include the hippocampus, subthalamic nucleus, caudate nucleus, centromedian nucleus, and anterior nucleus of the thalamus (ANT). Recently the results of a large randomized controlled trial, the electrical Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial, were published, demonstrating a significant reduction in mean seizure frequency with ANT stimulation. Soon after, in 2011, the results of a second randomized, controlled trial-the NeuroPace RNS trial-were published. The RNS trial examined closed-loop, responsive cortical stimulation of seizure foci in patients with refractory partial epilepsy, again finding significant reduction in seizure frequency. In the present review, the authors examine the modern history of electrical stimulation of the brain for the treatment of epilepsy and discuss the results of 2 important, recently published trials, the SANTE and RNS trials.

Prospective Trial of a Short Hospital Stay Protocol After Endoscopic Endonasal Pituitary Adenoma Surgery

OBJECTIVE Patients typically remain hospitalized for several days after transsphenoidal surgery for pituitary adenoma resection for reasons including pain control, serial neurological assessments, surveillance for cerebrospinal fluid leak, and management of endocrine issues. We sought to determine whether an evidence-based perioperative care protocol combined with an endoscopic approach could lead to routine and safe discharge on postoperative day 1. METHODS Our multidisciplinary pituitary group prospectively implemented a perioperative care protocol that emphasizes patient education, early mobilization, and scheduled inpatient and outpatient endocrine assessments on 50 consecutive patients who underwent surgical resection of a pituitary adenoma (82% macroadenomas, 2.1 ± 0.8 cm, maximum 4.5 cm, 18% microadenomas). Endoscopic endonasal surgery characterized by aggressive tumor resection and avoidance of nasal packing and lumbar drains was used in all cases. Lengths of stay, readmissions, and postoperative outcomes were analyzed. RESULTS Using the short-stay protocol, 92% (46 of 50) of patients were successfully discharged on postoperative day 1. The average length of stay for all patients was 1.16 ± 0.55 days (range 1 to 4). Postoperative diabetes insipidus occurred in 16% of patients (8 of 50), was effectively managed on an outpatient basis, and did not delay discharge. Readmission was required in 2 patients, in both cases for delayed presentation of a cerebrospinal fluid leak. CONCLUSIONS A short-stay protocol allows for an overnight hospital stay for patients after pituitary surgery, with a low rate of complications or readmission. This study offers evidence-based guidelines that may be used to avoid complications and facilitate early discharge after transsphenoidal surgery.

Iatrogenic Creutzfeldt-Jakob disease via surgical instruments

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative prion disease that can spread via contaminated neurosurgical instruments previously used on an infected patient. We examine current guidelines on how to recognize, handle, and prevent instrument-related iatrogenic CJD. Despite only four reported patients worldwide implicating contaminated neurosurgical instruments, and none in the past 30 years, the public health consequences of potential instrument-related iatrogenic CJD can be far-reaching. Conventional sterilization and disinfection methods are inadequate in reducing prion infectivity of contaminated instruments, and World Health Organization recommendations for disinfection using bleach or sodium hydroxide are often impractical for routine decontamination. Recently, possible CJD exposure via infected surgical instruments was suspected at a large teaching hospital. Although CJD was later disproven, the intervening investigation exposed the difficulty in tracking infected surgical instruments and in protecting subsequent surgical patients from prion infection. To identify patients at risk for iatrogenic CJD, infectivity of instruments after this index patient is estimated using simple scenario modeling, assuming a certain log reduction of infectivity for each cleansing cycle. Scenario modeling predicts that after six cycles of instrument use with conventional cleansing following an index patient, other patients are highly unlikely to be at risk for iatrogenic CJD. Despite its rarity, the threat of iatrogenic CJD transmission via contaminated instruments poses tremendous challenges to neurosurgeons. Basic prevention strategies should be employed for patients with suspected CJD, including use of disposable instruments where possible and quarantining non-disposable instruments until the diagnosis is ascertained, or using special instrument reprocessing methods if CJD is suspected.

Fixation with C-2 laminar screws in occipitocervical or C1–2 constructs in children 5 years of age or younger: a series of 18 patients

UNLABELLED OBJECT.: There are rare indications for upper cervical spine fusion in young children. Compared with nonrigid constructs, rigid instrumentation with screw fixation increases the fusion rate and reduces the need for halo fixation. Instrumentation may be technically challenging in younger children. A number of screw placement techniques have been described. Use of C-2 translaminar screws has been shown to be anatomically feasible, even in the youngest of children. However, there are few data detailing the clinical outcome. In this study, the authors describe the clinical and radiographic follow-up of 18 children 5 years of age or younger who had at least one C-2 translaminar screw as part of an occipitocervical or C1-2 fusion construct. METHODS A retrospective review of all children treated with instrumented occipitocervical or C1-2 fusion between July 1, 2007, and June 30, 2013, at Riley Childrens Hospital and Texas Childrens Hospital was performed. All children 5 years of age or younger with incorporation of at least one C-2 translaminar screw were identified. RESULTS Eighteen children were studied (7 boys and 11 girls). The mean age at surgery was 38.1 months (range 10-68 months). Indications for surgery included traumatic instability (6), os odontoideum (3), destructive processes (2), and congenital instability (7). A total of 24 C-2 translaminar screws were placed; 23 (95.8%) of 24 were satisfactorily placed (completely contained within the cortical walls). There was one medial cortex breach without neurological impingement. There were no complications with screw placement. Three patients required wound revisions. Two patients died as a result of their original condition (trauma, malignant tumor). The mean follow-up duration for the surviving patients was 17.5 months (range 3-60 months). Eleven (91.7%) of the 12 patients followed for 6 months or longer showed radiographic stability or completed fusion. CONCLUSIONS Use of C-2 translaminar screws provides an effective anchor for internal fixation of the upper cervical spine. In this study of children 5 years of age or younger, the authors found a high rate of radiographic fusion with a low rate of complications.

Endoscopic resection of tuberculum sellae meningiomas.

Objective To evaluate the results of endoscopic transnasal resection of tuberculum sellae meningiomas (TSMs) as compared with transcranial approaches. Design We retrospectively analyzed five patients who underwent endoscopic endonasal resection of TSM and performed a comprehensive review of articles published between 2000 and 2012 describing the operative treatment of TSMs. Results Gross total resection (GTR) was achieved in four patients (80%). Transient diabetes insipidus occurred in three patients (60%). Preoperative visual field deficit resolved in all patients. Cerebrospinal fluid (CSF) leak occurred in one patient. Analysis of published studies included 1,026 transcranial and 144 transnasal cases. GTR was achieved in 85% of transcranial and 72% of transnasal cases. Visual field deficit improved in 65% of transcranial and 82% of transnasal cases. Rate of diabetes insipidus and CSF leak was higher in the transnasal series. Rate of GTR and visual improvement was higher in endoscopic endonasal as compared with microsurgical transnasal series. Conclusion The literature supports transsphenoidal surgery for the resection of TSMs with significant optic nerve compromise and limited lateral extension. This approach may have an equivalent if not superior outcome over transcranial surgery in visual outcome. CSF leaks are still a challenge but may improve with the use of vascularized nasoseptal flaps.

Laser interstitial thermal therapy for newly diagnosed and recurrent glioblastoma

OBJECTIVE Glioblastoma (GBM) is the most common and deadly malignant primary brain tumor. Better surgical therapies are needed for newly diagnosed GBMs that are difficult to resect and for GBMs that recur despite standard therapies. The authors reviewed their institutional experience of using laser interstitial thermal therapy (LITT) for the treatment of newly diagnosed or recurrent GBMs. METHODS This study reports on the pre-LITT characteristics and post-LITT outcomes of 8 patients with newly diagnosed GBMs and 13 patients with recurrent GBM who underwent LITT. RESULTS Compared with the group with recurrent GBMs, the patients with newly diagnosed GBMs who underwent LITT tended to be older (60.8 vs 48.9 years), harbored larger tumors (22.4 vs 14.6 cm3), and a greater proportion had IDH wild-type GBMs. In the newly diagnosed GBM group, the median progression-free survival and the median survival after the procedure were 2 months and 8 months, respectively, and no patient demonstrated radiographic shrinkage of the tumor on follow-up imaging. In the 13 patients with recurrent GBM, 5 demonstrated a response to LITT, with radiographic shrinkage of the tumor following ablation. The median progression-free survival was 5 months, and the median survival was greater than 7 months. CONCLUSIONS In carefully selected patients with recurrent GBM, LITT may be an effective alternative to surgery as a salvage treatment. Its role in the treatment of newly diagnosed unresectable GBMs is not established yet and requires further study.

Immediate development of a contralateral acute subdural hematoma following acute subdural hematoma evacuation

Contralateral hematoma formation following acute subdural hematoma (ASDH) evacuation is a well-described complication. The most common type of contralateral hematoma is an epidural hematoma. Rarely, ASDH develops on the contralateral side. We report an elderly woman who presented with a post-traumatic ASDH and underwent ipsilateral hematoma evacuation by craniotomy and subsequently developed a contralateral ASDH. Because of the potential consequences of a delayed ASDH, there should be a low threshold for early post-operative imaging following ASDH evacuation, especially in elderly patients and those with additional associated intracranial injuries.

Nuances in Localization and Surgical Treatment of Syringomyelia Associated with Fenestrated and Webbed Intradural Spinal Arachnoid Cyst: A Retrospective Analysis.

INTRODUCTION Intradural spinal arachnoid cysts (SACs) are among many etiologies for syringomyelia. Consequentially, neurologic symptoms arise such as pain, gait disturbance, and bladder dysfunction. Identification of SAC on magnetic resonance imaging (MRI) can be challenging, as SACs can be fenestrated or in the form of fine webs. METHODS Imaging and clinical data for 7 patients who underwent surgical treatment for SAC associated with syringomyelia were reviewed. All previous publications of this pathology were reviewed via MEDLINE search. RESULTS Seven patients with a mean age 59 years were found to have a SAC causing syringomyelia. Intraoperative exploration confirmed SAC appearances of fine webs or a fluid-filled loculation impinging on the spinal cord. Common presentations were back pain, gait disturbance, and bladder incontinence. Diagnosis was made by MRI, although in 3 cases, the SAC was not identified on the initial review. Computed tomography myelogram was performed in one case due to the enlarged syringomyelia and lack of obvious spinal cord compression. Thoracic laminectomy/laminoplasty was performed for all patients, centered at the level of a subtle indentation of the cord; the syringomyelia proper was not directly addressed. Postoperatively, all patients had complete resolution of their symptoms with MRI demonstrating resolution of the syringomyelia. CONCLUSIONS Careful evaluation of the MRI can demonstrate subtle indentation of the cord at the caudal or cephalad end of the syringomyelia and may obviate the need for additional imaging. Meticulous arachnoid dissection and establishment of good CSF flow is sufficient for resolution of the syringomyelia, averting the need for more aggressive procedures.

Surgical cannulation of a cortical draining vein for endovascular treatment of a dural arteriovenous fistula of the cavernous sinus

Dural arteriovenous fistulas (DAVF) of the cavernous sinus most commonly present with ocular symptoms and can be observed or treated with endovascular approaches, surgery, or radiosurgery. Combined surgical-endovascular approaches have been used for fistulas that are not amenable to standard endovascular approaches. A 40-year-old man presented with ocular symptoms from a cavernous sinus DAVF. Multiple previous transarterial and transvenous embolization attempts had failed. The patient underwent craniotomy for surgical exposure and cannulation of an arterialized sylvian vein. Subsequently he underwent coiling and onyx embolization of the DAVF. The intervention resulted in effective obliteration of the fistula. If a cavernous sinus DAVF is refractory to treatment, surgical exposure and cannulation of a cortical draining vein can facilitate transvenous endovascular treatments.

Ionizing radiation augments glioma tropism of mesenchymal stem cells

OBJECTIVE Mesenchymal stem cells (MSCs) have been shown to localize to gliomas after intravascular delivery. Because these cells home to areas of tissue injury, the authors hypothesized that the administration of ionizing radiation (IR) to tumor would enhance the tropism of MSCs to gliomas. Additionally, they sought to identify which radiation-induced factors might attract MSCs. METHODS To assess the effect of IR on MSC migration in vitro, transwell assays using conditioned medium (CM) from an irradiated commercially available glioma cell line (U87) and from irradiated patient-derived glioma stem-like cells (GSCs; GSC7-2 and GSC11) were employed. For in vivo testing, green fluorescent protein (GFP)-labeled MSCs were injected into the carotid artery of nude mice harboring orthotopic U87, GSC7-2, or GSC17 xenografts that were treated with either 0 or 10 Gy of IR, and brain sections were quantitatively analyzed by immunofluorescence for GFP-positive cells. These GSCs were used because GSC7-2 is a weak attractor of MSCs at baseline, whereas GSC17 is a strong attractor. To determine the factors implicated in IR-induced tropism, CM from irradiated GSC7-2 and from GSC11 was assayed with a cytokine array and quantitative ELISA. RESULTS Transwell migration assays revealed statistically significant enhanced MSC migration to CM from irradiated U87, GSC7-2, and GSC11 compared with nonirradiated controls and in a dose-dependent manner. After their intravascular delivery into nude mice harboring orthotopic gliomas, MSCs engrafted more successfully in irradiated U87 (p = 0.036), compared with nonirradiated controls. IR also significantly increased the tropism of MSCs to GSC7-2 xenografts (p = 0.043), which are known to attract MSCs only poorly at baseline (weak-attractor GSCs). Ionizing radiation also increased the engraftment of MSCs in strong-attractor GSC17 xenografts, but these increases did not reach statistical significance. The chemokine CCL2 was released by GSC7-2 and GSC11 after irradiation in a dose-dependent manner and mediated in vitro transwell migration of MSCs. Immunohistochemistry revealed increased CCL2 in irradiated GSC7-2 gliomas near the site of MSC engraftment. CONCLUSIONS Administering IR to gliomas enhances MSC localization, particularly in GSCs that attract MSCs poorly at baseline. The chemokine CCL2 appears to play a crucial role in the IR-induced tropism of MSCs to gliomas.