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Nader Pouratian and Susan Y. Bookheimer

The adjacency of intracranial pathology to canonical regions of eloquence has long been considered a significant source of potential morbidity in the neurosurgical care of patients. Yet, several reports exist of patients who undergo resection of gliomas or other intracranial pathology in eloquent regions without adverse effects. This raises the question of whether anatomical and intracranial location can or should be used as a means of estimating eloquence. In this review, the authors systematically evaluate the factors that are known to affect anatomical-functional relationships, including anatomical, functional, pathology-related, and modality-specific sources of variability. This review highlights the unpredictability of functional eloquence based on anatomical features alone and the fact that patients should not be considered ineligible for surgical intervention based on anatomical considerations alone. Rather, neurosurgeons need to take advantage of modern technology and mapping techniques to create individualized maps and management plans. An individualized approach allows one to expand the number of patients who are considered for and who potentially may benefit from surgical intervention. Perhaps most importantly, an individualized approach to mapping patients with brain tumors ensures that the risk of iatrogenic functional injury is minimized while maximizing the extent of resection.

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Ricky Medel, Nader Pouratian and W. Jeffrey Elias

As > 95,000 spinal drug-delivery devices have been implanted since their inception in the 1980s, the recognition of associated adverse effects is essential. Since 1985, numerous reports have described the presence of catheter-tip granulomas. In the current case, the authors describe a less frequent complication of epidural bupivacaine precipitation. Regardless of origin, these unusual lesions have been increasingly recognized as a rare but potentially devastating complication of intrathecal infusions.

A 34-year-old woman with an intrathecal pain-pump delivering fentanyl, bupivacaine, and clonidine for thoracic outlet syndrome presented with rapidly progressive neurological deficits and increasing neck and upper-extremity pain. Neuroimaging disclosed a C7–T1 mass that was thought to be a hematoma that occurred after a recent epidural steroid injection. On emergency surgical decompression by laminectomy, a chalky mass containing viscous fluid was identified surrounding an epidurally located catheter. Histopathological examination revealed a proteinaceous mass consistent with drug precipitate enveloped by fibrosis and mild inflammation. Postoperatively, the patient recovered with minimal neurological deficit. The presentation and clinical relevance are discussed in conjunction with a review of the pertinent literature.

Catheter-tip masses are a rare complication of implantable drug-delivery devices occurring in < 3% of all patients with intrathecal catheters. Regardless of the anatomical site, the most common presenting features are neurological deficits, worsening pain, and increasing requirements for pain medication. Expedient diagnosis and management are essential for physicians treating patients with spinal infusion devices to prevent significant neurological sequelae. Further investigation is warranted regarding the use of bupivacaine as an adjunct in permanent spinal infusion systems.

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Jason Sheehan and Nader Pouratian

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Nader Pouratian, Neal F. Kassell and Aaron S. Dumont

Intracerebral hemorrhage (ICH) is a lingering cause of significant mortality and morbidity rates in contemporary society. Despite its established burden, considerably less investigative attention has been devoted to the study of ICH than other forms of stroke. Only a limited number of clinical studies have been performed to examine the surgical (both craniotomy and minimally invasive) and medical management of patients with ICH. No consistently efficacious strategies have been identified through such investigations. Limitations in study design and execution have universally impaired the interpretation and impact of available data. Management of ICH unfortunately remains heterogeneous across institutions, and it continues to suffer from the lack of proven medical and surgical effectiveness. Urgently needed are further prospective randomized controlled trials in which investigators consider the shortcomings of previous endeavors in the management of ICH. In the present article the authors review the current management practices of ICH, discuss the controlled trials, and highlight recent trials and future avenues of further study.

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R. Webster Crowley, Nader Pouratian and Jason P. Sheehan

✓ Despite the implementation of increasingly aggressive surgery, chemotherapy, and fractionated radiotherapy for the treatment of glioblastoma multiforme (GBM), most therapeutic regimens have resulted in only modest improvements in patient survival. Gamma knife surgery (GKS) has become an indispensable tool in the primary and adjuvant management of many intracranial pathologies, including meningiomas, pituitary tumors, and arteriovenous malformations. Although it would seem that radiosurgical techniques, which produce steep radiation dose fall-off around the target, would not be well suited to treat these infiltrative lesions, a limited number of institutional series suggest that GKS might provide a survival benefit when used as part of the comprehensive management of GBM. This may largely be attributed to the observation that tumors typically recur within a 2-cm margin of the tumor resection cavity. Despite these encouraging results, enthusiasm for radiosurgery as a primary treatment for GBM is significantly tempered by the failure of the only randomized trial that has been conducted to yield any benefit for patients with GBM who were treated with radiosurgery. In this paper, the authors review the pathophysiological mechanisms of GKS and its applications for GBM management.

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Nader Pouratian, Davis L. Reames, Robert Frysinger and W. Jeff Elias

Object

The aim of this study was to assess risk factors for postoperative seizures after deep brain stimulation (DBS) lead implantation surgery and the impact of such seizures on length of stay and discharge disposition.

Methods

The authors reviewed a consecutive series of 161 cases involving patients who underwent implantation of 288 electrodes for treatment of movement disorders at a single institution to determine the absolute risk of postoperative seizures, to describe the timing and type of seizures, to identify statistically significant risk factors for seizures, and to determine whether there are possible indications for seizure prophylaxis after DBS lead implantation. The electronic medical records were reviewed to identify demographic details, medical history, operative course, and postoperative outcomes and complications. To evaluate significant associations between potential risk factors and postoperative seizures, both univariate and multivariate analyses were performed.

Results

Seven (4.3%) of 161 patients experienced postoperative seizures, all of which were documented to have been generalized tonic-clonic seizures. In 5 (71%) of 7 cases, patients only experienced a single seizure. Similarly, in 5 of 7 cases, patients experienced seizures within 24 hours of surgery. In 6 (86%) of the 7 cases, seizures occurred within 48 hours of surgery. Univariate analysis identified 3 significant associations (or risk factors) for postoperative seizures: abnormal findings on postoperative imaging (hemorrhage, edema, and or ischemia; p < 0.001), age greater than 60 years (p = 0.021), and transventricular electrode trajectories (p = 0.023). The only significant factor identified on multivariate analysis was abnormal findings on postoperative imaging (p < 0.0001, OR 50.4, 95% CI 5.7–444.3). Patients who experienced postoperative seizures had a significantly longer length of stay than those who were seizure free (mean ± SD 5.29 ± 3.77 days vs 2.38 ± 2.38 days; p = 0.002, Student 2-tailed t-test). Likewise, final discharge to home was significantly less likely in patients who experienced seizures after implantation (43%) compared with those patients who did not (92%; p = 0.00194, Fisher exact test).

Conclusions

These results affirm that seizures are an uncommon complication of DBS surgery and generally occur within 48 hours of surgery. The results also indicate that hemorrhage, edema, or ischemia on postoperative images (“abnormal” imaging findings) increases the relative risk of postoperative seizures by 30- to 50-fold, providing statistical credence to the long-held assumption that seizures are associated with intracranial vascular events. Even in the setting of a postimplantation imaging abnormality, long-term anticonvulsant therapy will not likely be required because none of our patients developed chronic epilepsy.

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Farnaz M. Gazoni, Nader Pouratian and Edward C. Nemergut

Object

Skull blockade for craniotomy may result in the reduction of sympathetic stimulation associated with the application of head pins (“pinning”), improvement in intraoperative hemodynamic stability, and a decrease in intraoperative anesthetic requirements. Postoperative benefits may include a decrease in pain, in analgesic requirements, and in the incidence of nausea and vomiting. The authors examined the potential benefits of a skull block in patients in whom a maintenance anesthetic consisting of sevoflurane and a titratable remifentanil infusion was used. In other studies examining the ability of a skull block to improve perioperative outcomes, investigators have not used remifentanil.

Methods

Thirty patients presenting for resection of a supratentorial tumor were prospectively enrolled. Patients were randomized into 2 groups as follows: 14 patients (skull block group) received a skull block with 0.5% ropivacaine at least 15 minutes prior to pinning, whereas the remaining 16 patients (control group) did not.

Results

Patients in the skull block group did not have a significant increase in blood pressure or heart rate with placement of head pins, whereas patients in the control group did. Nevertheless, there was no difference in blood pressure variability between the groups. The mean intraoperative concentration of sevoflurane (1.0% in both groups, p = 0.703) and remifentanil (0.163 μg/kg/min compared with 0.205 μg/kg/min, p = 0.186) used was similar in both groups. During the postoperative period, there was no difference in the 1-, 2-, or 4-hour visual analog scale scores; in the need for postoperative narcotic analgesia (0.274 morphine equivalent mg/kg compared with 0.517 morphine equivalent mg/kg, p = 0.162); or in the incidence of nausea or vomiting.

Conclusions

Prospective analysis of perioperative skull blockade failed to demonstrate significant benefit in patients treated with a remifentanil infusion.

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Jason Sheehan, Anne Eischeid, Randi Saunders and Nader Pouratian

Object

Immunosuppressive agents are believed to play a role in recovery from spinal cord injury, but the underlying mechanisms by which neuronal function is improved by these agents are poorly understood. In this study, the authors evaluate the effect of immunosuppressive medications on neurite outgrowth and cell survival after a pharmacologically induced injury.

Methods

Differentiated human neuroblastoma SH-SY5Y cells were injured using the calcium agonist thapsigargin. After cellular injury, neurite outgrowth in the presence or absence of immunosuppressive agents was measured. Apoptosis was quantified with the aid of a terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling assay.

Neurite outgrowth was severely restricted following thapsigargin injury. Outgrowth was potentiated, however, by the addition of concentrations of 1 and 10 μM cyclosporin A in a dose-dependent fashion. Similarly, addition of 10 nM FK506 increased the percentage of neurites in the 20- to 40-micron range. A low dose (1 μM) of dexamethasone did not have a significant effect on neurite outgrowth, but a higher dose (10 μM) increased the percentage of neurites in the 10- to 45-micron range. These agents also lessened the degree of thapsigargin-induced apoptosis.

Conclusions

Immunosuppressive agents such as cyclosporin A, FK506, and dexamethasone can potentiate neurite outgrowth and protect against apoptotic cell death in a human postmitotic neuronal cell line. Such effects may have implications for lessening neuronal injury after neurotrauma, stroke, or neurodegeneration.

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Roy A. E. Bakay and Prasad S. S. V. Vannemreddy

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Nader Pouratian, Andrew F. Cannestra, Susan Y. Bookheimer, Neil A. Martin and Arthur W. Toga

Object. Electrocortical stimulation mapping is regarded as the gold standard of intraoperative mapping for predicting functional outcomes. Nevertheless, methodologies across institutions are inconsistent. Although many vary and maximize stimulation currents at each cortical site, some use a single current level to map the entire exposed cortex. The former comes at the cost of possibly inducing additional afterdischarge activity. The authors retrospectively reviewed their experience with intraoperative electrocortical stimulation mapping to characterize variability of both mapping and afterdischarge thresholds.

Methods. Seventeen patients satisfied the study inclusion criteria. Significant variability in mapping thresholds was identified within individuals and across the patient population. Moreover, a statistically significant difference in mapping thresholds was demonstrated between the frontal and parietal/temporal lobes (p = 0.007, one-way analysis of variance). The authors report a surprisingly high incidence of afterdischarge during mapping, wide variability in afterdischarge thresholds within individuals and across the study population, and mapping thresholds regularly exceeding afterdischarge thresholds in neighboring cortex. Differences in afterdischarge thresholds across lobes only approached significance (p = 0.086).

Conclusions. To maximize identification of eloquent cortices in some clinical situations, it may be advantageous to maximize currents at each cortical site regardless of adjacent afterdischarge threshold rather than to map the entire exposed cortex at a single current level. Moreover, the current findings highlight the need for electrocorticography during electrocortical stimulation mapping, both to identify when afterdischarges occur and to verify stimulation by recording stimulation artifacts. The advantages and limitations of maximizing currents at each cortical site as well as mapping at a single current level are discussed.