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Magnetoencephalography (MEG) is clinically used to help localize interictal spikes in discrete brain areas through the equivalent current dipole (ECD) method for patients with refractory epilepsy. The propagation of interictal spikes in adjacent regions was shown to be correlated with worse surgical outcomes in patients with temporal lobe epilepsy (TLE). Yet, the ECD method does not account for the temporal dynamics of spike activity, making it challenging to define the margins of the interictal network. Furthermore, the ECD results can be affected by states of arousal or sleep that alter background MEG activity.In this study, we developed a module in the custom-built Multi-Modal Analysis and Visualization Tool (MMVT) that analyzes the spatiotemporal dynamics of interictal spikes and removes normal variations associated with sleep. We analyzed MEG data from seven TLE patients and characterized their interictal spatiotemporal dynamics. In all patients, the onset of interictal spike activity appeared near the determined site of the epileptogenic zone based on corresponding neuroimaging and EEG data. The propagated source activity by 10 ms ranged from near the region of onset to spreading to extratemporal regions, such as the frontal lobe or insula.We demonstrated the feasibility of a novel method to assess the spatiotemporal properties of interictal spikes in patients with medically refractory TLE and to better delineate their onset and propagation patterns on MEG analysis. In doing so, we illustrate how variable the spike propagation distribution and speed may be within a 10 ms window. This visualization of the time component of the interictal networks offers an advantage over the currently used ECD method in characterizing the epileptic network and may help better guide surgical planning and provide for improved interventional outcomes in patients with TLE.

Background Idiopathic spinal cord herniation is a disorder in which the spinal cord herniates through a dural defect. We present a case in which both the standard surgical method and a salvage method failed. Case Description A 36-year-old man presented with 2 years of progressive numbness and proximal hip flexion weakness of both lower extremities. Magnetic resonance imaging of the thoracic spine was suggestive for a ventral spinal cord herniation at the T6/7 level. He was initially treated with reduction of his cord herniation, placement of a ventral sling of collagen matrix over the dural defect to prevent re-herniation, with a laminoplasty. He developed a blood-pressure-dependent paraparesis that did not recover despite a return to the operating room (OR) for removal of the laminoplastic bone flap. He was again taken to the OR, the sling was removed and we enlarged the ventral dural defect rostrally and caudally to prevent strangulation of the hernia as described by Watanabe. Though in the short term he was able to recover and transfer to physical therapy, after going home he developed lower extremity weakness and low-pressure headaches. Magnetic resonance imaging showed a ventral epidural cerebrospinal fluid pocket retropulsing the spinal cord, as well as pockets of ventral cerebrospinal fluid collections remote from the surgery site. The patient returned to the OR and the initial surgery with the ventral sling was re-performed with resolution of the headaches; the patient was neurologically stable and transferred to rehabilitation. Long-term he developed left intercostal pain at the level of the surgery without radiological correlate. Conclusions In this patient there was no single satisfactory surgical treatment of his ventrally herniated spinal cord—partly related to the herniated component of the cord acting as a mass within a narrow canal at the apex of the thoracic kyphosis. We encountered previously unreported complications of the ventral defect widening technique of surgical treatment.

Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is becoming an increasingly used and more thoroughly understood method for real-time monitored thermal lesioning of tissue. It has found a particular niche in the treatment of medically refractory focal epilepsy for which it provides a less invasive alternative to craniotomy and resection for multiple pathologies such as mesial temporal lobe sclerosis, focal cortical dysplasia, cavernous malformations, hypothalamic hamartoma, and epileptogenic tumors. Stereotactic laser brain ablation is also an alternative to craniotomy for cortical resections in non-lesional epilepsy as well as to disconnection surgery as in corpus callosotomy. Clinical investigations have focused on understanding the advantages as well as limitations of using MRg-LITT in epilepsy surgery, especially for mesial temporal sclerosis (MTS), which has been the most studied etiology. Though laser ablation for MTS shows a good safety and efficacy profile compared to open surgery, the minimally invasive nature of this technique is also an attractive and promising method both for practitioners and patients for surgical treatment of multiple etiologies of focal epilepsy.

We sought to determine whether the presence or surgical removal of certain nodes in a connectivity network constructed from intracranial electroencephalography recordings determines postoperative seizure freedom in surgical epilepsy patients.We analyzed connectivity networks constructed from peri-ictal intracranial electroencephalography of surgical epilepsy patients before a tailored resection. Thirty-six patients and 123 seizures were analyzed. Their Engel class postsurgical seizure outcome was determined at least one year after surgery. Betweenness centrality, a measure of a node's importance as a hub in the network, was used to compare nodes.The presence of larger quantities of high-betweenness nodes in interictal and postictal networks was associated with failure to achieve seizure freedom from the surgery (p 0.001), as was resection of high-betweenness nodes in three successive frequency groups in mid-seizure networks (p 0.001).Betweenness centrality is a biomarker for postsurgical seizure outcomes. The presence of high-betweenness nodes in interictal and postictal networks can predict patient outcome independent of resection. Additionally, since their resection is associated with worse seizure outcomes, the mid-seizure network high-betweenness centrality nodes may represent hubs in self-regulatory networks that inhibit or help terminate seizures.This is the first study to identify network nodes that are possibly protective in epilepsy.

Endoscopic endonasal surgery has been established as the safest approach to pituitary tumors, yet its role in other common skull base lesions has not been established. To answer this question, we carried out a systematic review of reported series of open and endoscopic endonasal approaches to four major skull base tumors: olfactory groove meningiomas (OGM), tuberculum sellae meningiomas (TSM), craniopharyngiomas (CRA), and clival chordomas (CHO). Data from 162 studies containing 5,701 patients were combined and compared for differences in perioperative mortality, gross total resection (GTR), cerebrospinal fluid (CSF) leak, neurological morbidity, post-operative visual function, post-operative anosmia, post-operative diabetes insipidus (DI), and post-operative obesity/hyperphagia. Weighted average rates for each outcome were calculated using relative study size. Our findings indicate similar rates of GTR and perioperative mortality between open and endoscopic approaches for all tumor types. CSF leak was increased after endoscopic surgery. Visual function symptoms were more likely to improve after endoscopic surgery for TSM, CRA, and CHO. Post-operative DI and obesity/hyperphagia were significantly increased after open resection in CRA. Recurrence rates per 1,000 patient-years of follow-up were higher in endoscopy for OGM, TSM, and CHO. Trends for open and endoscopic surgery suggested modest improvement in all outcomes over time. Our observations suggest that endonasal endoscopy is a safe alternative to craniotomy and may be preferred for certain tumor types. However, endoscopic surgery is associated with higher rates of CSF leak, and possibly increased recurrence rates. Prospective study with long-term follow-up is required to verify these preliminary observations.

Recombinant human bone morphogenetic protein–2 (rhBMP-2) promotes the induction of bone growth and is widely used in spine surgery to enhance arthrodesis. Recombinant human BMP-2 has been associated with a variety of complications including ectopic bone formation, adjacent-level fusion, local bone resorption, osteolysis, and radiculitis. Some of the complications associated with rhBMP-2 may be the result of rhBMP-2 induction of the inflammatory host response. In this paper the authors report on a patient with prior transforaminal lumbar interbody fusion (TLIF) using an interbody cage packed with rhBMP-2, in which rhBMP-2 possibly contributed to vascular injury during an attempted anterior lumbar interbody fusion. This 63-year-old man presented with a 1-year history of worsening refractory low-back pain and radiculopathy caused by a Grade 1 spondylolisthesis at L4–5. He underwent an uncomplicated L4–5 TLIF using an rhBMP-2–packed interbody cage. Postoperatively, he experienced marginal improvement of his symptoms. Within the next year and a half the patient returned with unremitting low-back pain and neurogenic claudication that failed to respond to conservative measures. Radiological imaging of the patient revealed screw loosening and pseudarthrosis. He underwent an anterior retroperitoneal approach with a plan for removal of the previous cage, complete discectomy, and placement of a femoral ring. During the retroperitoneal approach the iliac vein was adhered with scarring and fibrosis to the underlying previously operated L4–5 interbody space. During mobilization the left iliac vein was torn, resulting in significant blood loss and cardiac arrest requiring chest compression, defibrillator shocks, and blood transfusion. The patient was stabilized, the operation was terminated, and he was transferred to the intensive care unit. He recovered over the next several days and was discharged at his neurological baseline. The authors propose that the rhBMP-2–induced host inflammatory response partially contributed to vessel fibrosis and scarring, resulting in the life-threatening vascular injury during the reoperation. Spine surgeons should be aware of this potential inflammatory fibrosis in addition to other reported complications related to rhBMP-2.

Objectives To determine the anatomical relationships that may influence endonasal access to the upper cervical spine. Setting We retrospectively analyzed computed tomography of 100 patients at a single institution. Participants Participants included adults with imaging of the hard palate, clivus, and cervical spine without evidence of fracture, severe spondylosis, or previous instrumentation. Main Outcome Measures Morphometric analyses of hard palate length and both distance and angle between the hard palate and odontoid process were based on radiographic measurements. Descriptive zones were assigned to cervical spine levels, and endoscopic visualization was simulated with projected lines at 0, 30, and 45 degrees from the hard palate to the cervical spine. Results We found an inverse relationship between hard palate length and the lowest zone of the cervical spine potentially visualized by nasal endoscopy. The distance between the posterior tip of the hard palate and the odontoid tip, and the angle formed between the two, directly influenced the lowest possible cervical exposure. Conclusions Radiographic relationships between hard palate length, distance to the odontoid, and the angle formed between the two predict the limits of endonasal access to the cervical spine. These results are supported by cadaveric data in Part Two of this study.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by heterotopic ossification of soft connective and muscle tissues, often as the result of minor trauma. The sequelae include joint fusion, accumulation of calcified foci within soft tissues, thoracic insufficiency syndrome, and progressive immobility. The authors report on a patient with FOP who developed severe spinal canal stenosis in the thoracic spine causing substantial myelopathy. He underwent a thoracic laminectomy and resection of a large posterior osteophyte. Unique considerations are required in treating patients with FOP, including steroid administration to prevent ossification and anesthetic technique. The nuances of neurosurgical and medical management as they pertain to this disease are discussed.

Background and Purpose— Unruptured intracranial aneurysms (UIAs) are being identified more frequently and endovascular coil embolization has become an increasingly popular treatment modality. Our study evaluates patient outcomes with changing patterns of treatment of UIA. Methods— We conducted a retrospective, longitudinal cohort study of 3132 hospital discharges for UIA identified from the New York Statewide Database (SPARCS) in 2005 to 2007 and 2200 discharges from 1995 to 2000. The rates of endovascular coiling and surgical clipping were examined along with hospital variables and discharge outcome. Anatomic specifics of UIA were unavailable for analysis. Results— The case rate for treatment of UIA doubled from 1.59 (1995 to 2000) to 3.45 per 100 000 (2005 to 2007, P P P P P =0.168) and a worsening of good outcomes for clipping (76.3% versus 71.7%, P =0.0132). Conclusions— Despite coiling being associated with an increased incidence of good outcome relative to clipping of UIA, the increase in coiling has failed to improve overall patient outcome. The shift in coiling venue from high-volume centers to low-volume centers and decreasing microsurgical volume accompanied by a worsening in microsurgical results contribute to this. This argues for greater centralization of care.

Chronic subdural hematoma (cSDH) is an increasingly common neurological disease process. Despite the wide prevalence of cSDH, there remains a lack of consensus regarding numerous aspects of its clinical management. We provide an overview of the epidemiology and pathophysiology of cSDH and discuss several controversial management issues, including the timing of post-operative resumption of anticoagulant medications, the effectiveness of anti-epileptic prophylaxis, protocols for mobilization following evacuation of cSDH, as well as the comparative effectiveness of the various techniques of surgical evacuation. A PubMed search was carried out through October 19, 2010 using the following keywords: "subdural hematoma", "craniotomy", "burr-hole", "management", "anticoagulation", "seizure prophylaxis", "antiplatelet", "mobilization", and "surgical evacuation", alone and in combination. Relevant articles were identified and back-referenced to yield additional papers. A meta-analysis was then performed comparing the efficacy and complications associated with the various methods of cSDH evacuation. There is general agreement that significant coagulopathy should be reversed expeditiously in patients presenting with cSDH. Although protocols for gradual resumption of anti-coagulation for prophylaxis of venous thrombosis may be derived from guidelines for other neurosurgical procedures, further prospective study is necessary to determine the optimal time to restart full-dose anti-coagulation in the setting of recently drained cSDH. There is also conflicting evidence to support seizure prophylaxis in patients with cSDH, although the existing literature supports prophylaxis in patients who are at a higher risk for seizures. The published data regarding surgical technique for cSDH supports primary twist drill craniostomy (TDC) drainage at the bedside for patients who are high-risk surgical candidates with non-septated cSDH and craniotomy as a first-line evacuation technique for cSDH with significant membranes. Larger prospective studies addressing these aspects of cSDH management are necessary to establish definitive recommendations.

Object Cystathionine β-synthase (CBS) is an enzyme that metabolizes homocysteine to form H2S in the brain. Hydrogen sulfide functions as a vasodilator as well as a regulator of neuronal ion channels and multiple intracellular signaling pathways. Given the myriad effects of H2S, the authors hypothesized that patients possessing gain-of-function polymorphisms of the CBS gene will experience a decreased incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients were enrolled in a prospective observational database of aSAH outcomes. DNA was extracted from buccal swabs and sequenced for 3 functional polymorphisms of the CBS gene (699C→T, 844ins68, and 1080C→T) by polymerase chain reaction. Serum homocysteine levels (μmol/L) were assayed. Multivariate analysis was used to determine the relationship between CBS genotype and occurrence of both angiographic vasospasm and DCI. Results There were 87 patients included in the study. None of the polymorphisms investigated were significantly associated with the incidence of angiographic vasospasm. However, after controlling for admission hypertension, patients with the gain-of-function 844 WT/ins genotypes were less likely to experience DCI relative to those with the 844 WT/WT genotype (86 patients, p = 0.050), while the decrease-in-function genotype 1080 TT was more likely to experience DCI relative to those with 1080 CC and CT genotypes (84 patients, p = 0.042). Serum homocysteine levels did not correlate with the extent of either angiographic vasospasm or DCI in this analysis. Conclusions Polymorphisms of the CBS gene that impart gain-of-function may be associated with a reduced risk of DCI after aSAH, independent of serum homocysteine. Signaling through H2S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation.

Studies have reported improved seizure control with increased duration of vagus nerve stimulation (VNS) but are prone to methodological biases. We analyzed the efficacy of VNS over time in patients with treatment-resistant epilepsy (TRE) who underwent VNS therapy 10 or more years.We retrospectively reviewed 65 consecutive patients (29 females) who underwent VNS therapy ≥ 10 years. The mean age at VNS insertion was 30.0 years. Forty-four adults (≥ 18 years; 67.7%) and 21 children (32.3%) were included. Seizure frequency and antiepileptic drug (AED) regimens were recorded prior to VNS and, following VNS insertion, at 6 months, 1 year, 2 years, and every 2 years thereafter.The mean duration of VNS therapy for this group was 10.4 years, and the mean decrease in seizure frequency at last follow-up was 76.3%. The mean reduction in seizures at 6 months and years 1, 2, 4, 6, 8, and 10 years was 35.7, 52.1, 58.3, 60.4, 65.7, 75.5, and 75.5%, respectively. Seizure frequency was significantly reduced from baseline at each of the recorded intervals (P0.001). There was a trend toward increased AED burden in the latter years of the follow-up period.Following a "ramp-up" and accommodation period throughout the initial 24 months after VNS implantation, seizure control improved slightly over the subsequent years of therapy and eventually stabilized. Variation in seizure frequency, however, was common, and frequent changes in AED regimens or stimulation parameters were likely an important and possibly synergistic component of seizure control.

Objective Intraventricular hemorrhage (IVH) is associated with a poor outcome. External ventricular drainage together with clot lysis through intrathecal tissue plasminogen activator (IT-tPA) has been proposed as a promising therapy. However, recent experimental work has implicated tissue plasminogen activator (tPA) in the pathogenesis of cerebral edema. Methods We reviewed the records of all patients with IVH caused by primary supratentorial intracerebral hemorrhage who underwent external ventricular drainage without surgical evacuation between January 2001 and June 2008. Of these 30 patients, we identified 13 who received IT-tPA. The remaining 17 patients served as controls. Hemorrhage, edema volume, and IVH score were determined on admission and by follow-up computed tomographic scans for 96 hours after admission. Discharge outcome was evaluated using the modified Rankin Scale. Results There were no significant differences between the treatment and controls in terms of age, Glasgow Coma Scale score, Graeb and LeRoux IVH scores, or intracerebral hemorrhage volume on admission. IT-tPA resulted in more rapid clearance of IVH as determined by the 96-hour decrease in both the Graeb IVH score (tPA, 3.00 +/- .55; control, 1.00 +/- 0.57; P = .05) and the LeRoux IVH score (tPA, 6.2 +/- 0.80; control, 2.25 +/- 1.32; P = .05). Patients treated with IT-tPA demonstrated significantly larger peak ratios of edema to intracerebral hemorrhage volume (1.24 +/- 0.14 vs 0.70 +/- 0.08 in controls; P = .002). Additionally, increased rates of sterile meningitis (46% vs 12%; P = .049) and a trend toward shunt dependence (38% vs 6%; P = .06) were observed in the tPA cohort. Nevertheless, no significant differences in outcome at discharge or length of hospital stay were observed between cohorts. Conclusion Although IT-tPA hastens the resolution of IVH, it may worsen perihematomal edema formation. Larger prospective studies are required to confirm these findings and to determine whether outcome is adversely affected by IT-tPA administration.

Despite extensive effort to elucidate the cellular and molecular bases for delayed cerebral injury after aneurysmal subarachnoid hemorrhage (aSAH), the pathophysiology of these events remains poorly understood. Recently, much work has focused on evaluating the genetic underpinnings of various diseases in an effort to delineate the contribution of specific molecular pathways as well as to uncover novel mechanisms. The majority of subarachnoid hemorrhage genetic research has focused on gene expression and linkage studies of these markers as they relate to the development of intracranial aneurysms and their subsequent rupture. Far less work has centered on the genetic determinants of cerebral vasospasm, the predisposition to delayed cerebral injury, and the determinants of ensuing functional outcome after aSAH. The suspected genes are diverse and encompass multiple functional systems including fibrinolysis, inflammation, vascular reactivity, and neuronal repair. To this end, we present a systematic review of 21 studies suggesting a genetic basis for clinical outcome after aSAH, with a special emphasis on the pathogenesis of cerebral vasospasm and delayed cerebral ischemia. In addition, we highlight potential pitfalls in the interpretation of genetic association studies, and call for uniformity of design of larger multicenter studies in the future.

The goal of this study was to examine the relationship between race and outcome following subarachnoid hemorrhage (SAH). We identified all SAH discharges in New York City during 2003. An adverse outcome was defined as in-hospital death or discharge other than to home. While correcting for age and gender, we examined the effect of race and payor status on outcome following SAH. Forty-four percent of patients with SAH were white. Being white had a significant relationship with outcome when controlled for payor status (odds ratio 0.56). Among self-pay/Medicaid patients, fewer white (52%) individuals suffered poor outcomes than non-white (66%, p = 0.03). Our results establish that white patients in New York City with SAH have better outcomes than non-whites. While it is unclear whether this discrepancy is secondary to pathophysiological differences or unidentified social factors, our findings demonstrate that this effect is independent of insurance status, and emphasize the need for further investigation into racial disparities in outcome following SAH.

The clinical failure of neuroprotective agents stems partly from inappropriate statistical presentation of preclinical data, which causes an overestimation of effect size and underpowered clinical studies. We searched for studies utilizing neuroprotective agents in a rodent middle cerebral artery occlusion model. We identified all experimental groups demonstrating statistically significant claims of neuroprotection within these studies and calculated the mean, 95% confidence intervals (CI), and meta-analyses of effect size for each agent. The lower limits of the CI (LLCI) of effect size were less than 0.2 in 161/221 (73%) of all experimental groups, corresponding to small effects. After meta-analysis, 29/60 (48%) and 11/18 (61%) of the agents had an effect size LLCI < 0.2 for infarct volume and neurological function, respectively. This difference was statistically significant (p < 0.05). These results suggest that the preclinical neuroprotective effect size of many of these drugs is small, although that of neurological function is smaller and is thus a more conservative and appropriate estimate of effect.

Object Despite the prevalence of chronic subdural hematoma (CSDHs) in the rapidly growing elderly population, several aspects of disease management remain unclear. In particular, there is still conflicting evidence regarding the efficacy of antiepileptic drug (AED) prophylaxis in patients with CSDH who undergo bur hole drainage. The authors endeavored to evaluate the efficacy of AED prophylaxis in reducing the incidence of seizures and improving outcome in this patient population. Methods A single surgeon's clinical database (E.S.C.) was analyzed for cases involving bur hole drainage for CSDH. Cases involving nonhemorrhagic subdural effusions as well as acute subdural hemorrhages evacuated by craniotomy were excluded from this study. Patient medical records were evaluated for relevant demographic data, medical history, imaging characteristics, clinical details of the treatment, hospital stay, and discharge summaries. Results The authors included 88 patients with bur hole–treated CSDH. Eleven patients (12.5%) suffered at least 1 seizure between hemorrhage onset and discharge from their treatment hospital admission. Seizures were more frequent in women than men (p = 0.030) and least frequent in patients with right-sided lesions (p = 0.030). In a multiple logistic regression model, preoperative initiation of AED prophylaxis was the only significant predictor of the lower incidence of postoperative seizures (OR 0.10, p = 0.013). However, preoperative initiation of AED prophylaxis did not significantly affect outcome at discharge. Conclusions The finding in this study demonstrates that preoperative AED prophylaxis likely reduces the incidence of postoperative seizures in patients with CSDH treated with bur hole drainage. A future prospective randomized study is necessary to evaluate the effect of seizure reduction on clinical outcome.

Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Currently, no pharmacologic treatment strategies exist for this devastating disease. Following the initial mechanical injury suffered at hemorrhage onset, secondary brain injury proceeds through both direct cellular injury and inflammatory cascades, which trigger infiltration of granulocytes and monocytes, activation of microglia, and disruption of the blood-brain barrier with resulting cerebral edema. The complement cascade has been shown to play a central role in the pathogenesis of secondary injury following ICH, although the specific mechanisms responsible for the proximal activation of complement remain incompletely understood. Cerebral injury following cleavage of complement component 3 (C3) proceeds through parallel but interrelated pathways of anaphylatoxin-mediated inflammation and direct toxicity secondary to membrane attack complex-driven erythrocyte lysis. Complement activation also likely plays an important physiologic role in recovery following ICH. As such, a detailed understanding of the variation in functional effects of complement activation over time is critical to exploiting this target as an exciting translational strategy for intracerebral hemorrhage.

Background and Purpose— Acute kidney injury occurs in 1% to 25% of critically ill patients with small increases in creatinine adversely affecting outcome. We sought to determine the burden of acute kidney injury in patients with aneurysmal subarachnoid hemorrhage and whether this dysfunction affects outcome. Methods— Between 1996 and 2008, 787 consecutive patients with aneurysmal subarachnoid hemorrhage were enrolled in our prospective database. Demographics, serum creatinine levels, and discharge modified Rankin scores were recorded, and changes in creatinine clearance were calculated. A multiple logistic regression was performed using known predictors for poor outcome after aneurysmal subarachnoid hemorrhage in addition to burden of contrast-enhanced imaging and change in creatinine clearance. Results— One hundred seventy-nine (23.1%) patients were at risk for renal failure during their hospitalization. In a multivariate model, those patients who developed risk for renal failure were twice as likely to have a poor 3-month outcome (OR, 2.01; P =0.021). Survival curves comparing those not at risk, those at risk (increasing severity classes Risk, Injury, and Failure, and the 2 outcome classes Loss and End-Stage Kidney Disease [RIFLE] R), and those with renal injury or failure (RIFLE I and F) demonstrated that risk of death increases significantly as one progresses through the RIFLE classes (log rank, P Conclusions— In a large, consecutive series of prospectively enrolled patients with aneurysmal subarachnoid hemorrhage, we demonstrate, using the newly defined RIFLE classification for risk of renal failure, that even seemingly insignificant decreases in creatinine clearance are associated with significantly worse 3-month outcomes. This study highlights the importance of close surveillance of renal function and stresses the value of renal hygiene in the aneurysmal subarachnoid hemorrhage population.

Ischemic stroke remains one of the leading causes of death and disability in the developed world. Despite many promising preclinical results, the only pharmacologic treatments proven effective in improving clinical outcome following ischemic stroke until now are administration of aspirin and acute thrombolysis using tissue-plasminogen activator.To review currently approved pharmacologic therapies as well as promising future treatment strategies for acute ischemic stroke.We performed an exhaustive PubMed search for articles published from 1950 through 2009 describing pharmacotherapy of acute ischemic stroke, focusing on agents that are currently in Phase III trials or approved for clinical use. Following this review, we present our interpretation of the existing literature and our vision of the future of pharmacotherapy for ischemic stroke.Since the clinical success of the first intravenous thrombolytic, many studies have sought to further characterize the ideal patient population and to extend the therapeutic time window for pharmacologic thrombolysis. Additionally, despite the many failures of neuroprotective trials, several promising agents are currently undergoing Phase III investigation. With the advent of interventional techniques enabling local delivery of therapeutics into the region of the thrombus, the future of pharmacotherapy for ischemic stroke will probably include a combination of interventional techniques and pharmacotherapy.

Although the preponderance of cerebellopontine angle lesions are schwannomas, focused attention to patient clinical history, imaging studies, and tissue biopsies when indicated will aid in detection of less common lesions that might otherwise be misdiagnosed. This is most critical for pathologies that dictate different management paradigms be undertaken.

A 4-year-old girl with a history of thoracic meningocele repair at the age of 3 months presented with progressive myelopathy. An intramedullary thoracic epidermoid was identified on MRI. The patient underwent excision of the epidermoid and subsequently returned to neurological baseline. This case illustrates the potential for delayed development of intraspinal epidermoid after initial repair of a simple meningocele.

The Adhesive Removal (sticky-tape) test is a commonly used test of somatosensory dysfunction following cerebral ischemia in rats. This test requires several days of pre-training prior to surgery, which can be time consuming. We present our results with an improved version of the sticky-tape test. Male Wistar rats were subjected to either sham surgery (n = 4) or right middle cerebral artery occlusion (rMCAo) using an intraluminal filament (n = 9), followed by a 10-day survival period. On post-operative days (POD) 1, 3, 7, and 10 animals underwent both the conventional sticky-tape test (CST) with measurement of the time to remove the stimulus (trs), as well as a modified sticky-tape test (MST), in which a non-removable tape sleeve was placed around the animal's paw. Time spent attending to this stimulus (tas) was recorded. Despite 3 days of pre-training, animals undergoing baseline CST still exhibited marked variability in pre-operative baseline test performance (trs range 1-60s). In contrast, animals undergoing MST for the first time demonstrated nearly uniformly excellent performance (% tas range 91.5-98.5% of the 30s testing period). Although, affected (left) limb performance on both CST (6.8-fold increase in trs on POD 1 compared to baseline) and MST (100% decrease in tas on POD 1 compared to baseline) was markedly altered by rMCAo, CST performance declined bilaterally, and no significant differences in the ratio of affected (left) and unaffected (right) limb performance between sham-operated and rMCAo animals were observed at any time point. In contrast, the ratio of left to right performance on the MST was significantly different at all time points (P

In vivo rodent models of focal cerebral ischemia have been developed to investigate stroke therapy. Typically these models require rapid quantification of cerebral infarct volumes using vital stains with tetrazolium salts to delineate the extent of neuronal death. To avoid animal sacrifice, we sought a study with MR acquired volumetric rat data where surrogate of ground truth is obtained by repeated manual delineation by experts, and an automated hybrid segmentation is evaluated for accuracy. We propose a rating system for the expert delineations that captures intra- and inter-expert discrepancy. Our preliminary results show that surrogate ground truth derived from MR data is at least as good as the one derived from histologic stained slices. Hence animal sacrifice is not necessary to evaluate ischemic stroke automated segmentation in a rat model of temporary middle cerebral artery occlusion.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) promotes the induction of bone growth and is widely used in spine surgery to enhance arthrodesis. Recombinant human BMP-2 has been associated with a variety of complications including ectopic bone formation, adjacent-level fusion, local bone resorption, osteolysis, and radiculitis. Some of the complications associated with rhBMP-2 may be the result of rhBMP-2 induction of the inflammatory host response. In this paper the authors report on a patient with prior transforaminal lumbar interbody fusion (TLIF) using an interbody cage packed with rhBMP-2, in which rhBMP-2 possibly contributed to vascular injury during an attempted anterior lumbar interbody fusion. This 63-year-old man presented with a 1-year history of worsening refractory low-back pain and radiculopathy caused by a Grade 1 spondylolisthesis at L4-5. He underwent an uncomplicated L4-5 TLIF using an rhBMP-2-packed interbody cage. Postoperatively, he experienced marginal improvement of his symptoms. Within the next year and a half the patient returned with unremitting low-back pain and neurogenic claudication that failed to respond to conservative measures. Radiological imaging of the patient revealed screw loosening and pseudarthrosis. He underwent an anterior retroperitoneal approach with a plan for removal of the previous cage, complete discectomy, and placement of a femoral ring. During the retroperitoneal approach the iliac vein was adhered with scarring and fibrosis to the underlying previously operated L4-5 interbody space. During mobilization the left iliac vein was torn, resulting in significant blood loss and cardiac arrest requiring chest compression, defibrillator shocks, and blood transfusion. The patient was stabilized, the operation was terminated, and he was transferred to the intensive care unit. He recovered over the next several days and was discharged at his neurological baseline. The authors propose that the rhBMP-2-induced host inflammatory response partially contributed to vessel fibrosis and scarring, resulting in the life-threatening vascular injury during the reoperation. Spine surgeons should be aware of this potential inflammatory fibrosis in addition to other reported complications related to rhBMP-2.

Intensive care units (ICU) specializing in the treatment of patients with neurological diseases (Neuro-ICU) have become increasingly common. However, there are few data on the longitudinal demographics of this patient population. Identifying admission trends may provide targets for improving resource utilization. We performed a retrospective analysis of admission logs for primary diagnosis, age, sex, and length of stay, for all patients admitted to the Neuro-ICU at Columbia University Medical Center (CUMC) between 2000 and 2008. From 2000 to 2008, inclusive, the total number of Neuro-ICU admissions increased by 49.9%. Overall mean patient age (54.6 ± 17.4 to 56.2 ± 18.0 years, p=0.041) and gender (55.9-50.3% female, p=0.005) changed significantly, while median length of stay (2 days) did not. When comparing the time period prior to construction of a larger Neuro-ICU (2000-2004) to that after completion (2005-2008), patient age (56.0 ± 17.6 compared to 56.9 ± 17.5 years, p=0.012) and median length of stay (1 compared to 2 days, p

Patients receiving antiplatelet medications are reported to be at increased risk for hematoma enlargement and worse clinical outcomes following intracerebral hemorrhage (ICH). While platelet transfusions are frequently administered to counteract qualitative platelet defects in the setting of ICH, conclusive evidence in support of this therapeutic strategy is lacking. In fact, platelet transfusions may be associated with adverse effects, and represent a finite resource. We sought to determine the clinical efficacy of platelet transfusion and its impact on systemic complications following ICH in a cohort of patients receiving antiplatelet medications.We retrospectively analysed the medical records of 66 patients admitted to our institution from June 2003 to July 2008 who suffered a primary ICH while receiving antiplatelet (acetylsalicylic acid and/or clopidogrel) therapy. The primary outcome was the rate of significant (25% increase from admission) hematoma expansion in transfused (n=35) versus non-transfused (n=31) patients. Discharge modified-Rankin score (mRS) and the rates of systemic complications were also assessed.There were no statistically significant differences in rates of hematoma expansion between cohorts, nor were there differences in demographic variables, systemic complications or discharge mRS. Subgroup analysis revealed that there was a higher rate of hematoma expansion in the clopidogrel cohort (p=0.034) than in the cohort of patients receiving aspirin alone.This study suggests that platelet administration does not reduce the frequency of hematoma expansion in ICH patients receiving antiplatelet medications. This lack of efficacy may relate to transfusion timing, as a significant proportion of hematoma expansion occurs within 6 hours post-ictus. Additionally, the increased rates of hematoma expansion in the clopidogrel cohort may relate to its prolonged half-life. A larger, prospective study is warranted.

Aneurysmal subarachnoid hemorrhage (aSAH) is a form of hemorrhagic stroke that affects up to 30,000 individuals per year in the United States. The incidence of aSAH has been shown to be associated with numerous nonmodifiable (age, gender, ethnicity, family history, aneurysm location, size) and modifiable (hypertension, body mass index, tobacco and illicit drug use) risk factors. Although early repair of ruptured aneurysms and aggressive postoperative management has improved overall outcomes, it remains a devastating disease, with mortality approaching 50% and less than 60% of survivors returning to functional independence. As treatment modalities change and the percentage of minority and elderly populations increase, it is critical to maintain an up-to-date understanding of the epidemiology of SAH.

TNF-alpha is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-alpha may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH).We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8h and recorded at the same point that brain interstitial fluid TNF-alpha was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations.Each patient had a mean of 9 brain tissue TNF-alpha measurements obtained over an average of 72h of monitoring. TNF-alpha levels rose progressively over time. Predictors of elevated brain interstitial TNF-alpha included higher brain interstitial fluid glucose levels (beta=0.066, p0.02), intraventricular hemorrhage (beta=0.085, p0.021), and aneurysm size6mm (beta=0.14, p0.001). There was no relationship between TNF-alpha levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio.Brain interstitial TNF-alpha levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels.

Despite the prevalence of chronic subdural hematoma (CSDHs) in the rapidly growing elderly population, several aspects of disease management remain unclear. In particular, there is still conflicting evidence regarding the efficacy of antiepileptic drug (AED) prophylaxis in patients with CSDH who undergo bur hole drainage. The authors endeavored to evaluate the efficacy of AED prophylaxis in reducing the incidence of seizures and improving outcome in this patient population.A single surgeon's clinical database (E.S.C.) was analyzed for cases involving bur hole drainage for CSDH. Cases involving nonhemorrhagic subdural effusions as well as acute subdural hemorrhages evacuated by craniotomy were excluded from this study. Patient medical records were evaluated for relevant demographic data, medical history, imaging characteristics, clinical details of the treatment, hospital stay, and discharge summaries.The authors included 88 patients with bur hole-treated CSDH. Eleven patients (12.5%) suffered at least 1 seizure between hemorrhage onset and discharge from their treatment hospital admission. Seizures were more frequent in women than men (p = 0.030) and least frequent in patients with right-sided lesions (p = 0.030). In a multiple logistic regression model, preoperative initiation of AED prophylaxis was the only significant predictor of the lower incidence of postoperative seizures (OR 0.10, p = 0.013). However, preoperative initiation of AED prophylaxis did not significantly affect outcome at discharge.The finding in this study demonstrates that preoperative AED prophylaxis likely reduces the incidence of postoperative seizures in patients with CSDH treated with bur hole drainage. A future prospective randomized study is necessary to evaluate the effect of seizure reduction on clinical outcome.

Introduction Giant pituitary adenomas of excessive size, fibrous consistency or unfavorable geometric configuration may be unresectable through conventional operative approaches. We present our select case series for operative resection and long-term follow-up for these unusual tumors, employing both a staged procedure and a combined transsphenoidal-transcranial above and below approach. Method A retrospective chart review was performed on patients operated via the staged, and combined approaches by the senior author (J.N·B.). Preoperative characteristics and postoperative outcomes were reviewed. A detailed description of the operative technique and perioperative management is provided. Results Between 1993 and 1996, two patients harboring giant pituitary adenomas underwent an intentionally staged resection, and between 1997 and 2006, nine patients harboring giant pituitary adenomas underwent surgery via a single-stage above and below approach. Nine patients (82%) presented with non-secreting adenomas and two patients (18%) presented with prolactinomas refractory to medical management. Gross total resection was achieved in six patients (55%), near total resection in 1 (9%), and subtotal removal in 4 (36%). Seven patients (64%) experienced visual improvement postoperatively and no major complications occurred. Long-term follow-up averaged 51.6 months. Panhypopituitarism was observed in four patients, partial hypopituitarism in four, persistent DI in two, and persistent SIADH in one. Conclusions The addition of a transcranial component to the transsphenoidal approach offers additional visualization of critical neurovascular structures during giant pituitary adenoma resection. Complications rates are similar to other series in which complex pituitary adenomas are resected by other means. The above and below approach is both safe and effective and the immediate and long-term advantages of a single-stage approach justify its utility in this select group of patients.

Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA.

A segmentation method that quantifies cerebral infarct using rat data with ischemic stroke is evaluated using ground truth from histologic and MR data. To demonstrate alternative approach to rapid quantification of cerebral infarct volumes using histologic stained slices that requires scarifying animal life, a study with MR acquire volumetric rat data is proposed where ground truth is obtained by manual delineations by experts and automated segmentation is assessed for accuracy. A framework for evaluation of segmentation is used that provides more detailed accuracy measurements than mere cerebral infarct volume. Our preliminary experiment shows that ground truth derived from MRI data is at least as good as the one obtained from the histologic slices for evaluating segmentation algorithms for accuracy. Therefore we can develop and evaluate automated segmentation methods for rapid quantification of stroke without the necessitating animal sacrifice.