Visualization of the Spatiotemporal Propagation of Interictal Spikes in Temporal Lobe Epilepsy: A MEG Pilot Study.

Magnetoencephalography (MEG) is clinically used to localize interictal spikes in discrete brain areas of epilepsy patients through the equivalent current dipole (ECD) method, but does not account for the temporal dynamics of spike activity. Recent studies found that interictal spike propagation beyond the temporal lobe may be associated with worse postsurgical outcomes, but studies using whole-brain data such as in MEG remain limited. In this pilot study, we developed a tool that visualizes the spatiotemporal dynamics of interictal MEG spikes normalized to spike-free sleep activity to assess their onset and propagation patterns in patients with temporal lobe epilepsy (TLE). We extracted interictal source data containing focal epileptiform activity in awake and asleep states from seven patients whose MEG ECD clusters localized to the temporal lobe and normalized the data against spike-free sleep recordings. We calculated the normalized activity over time per cortical label, confirmed maximal activity at onset, and mapped the activity over a 10 ms interval onto each patient's brain using a custom-built Multi-Modal Visualization Tool. The onset of activity in all patients appeared near the clinically determined epileptogenic zone. By 10 ms, four of the patients had propagated source activity restricted to within the temporal lobe, and three had propagated source activity spread to extratemporal regions. Using this tool, we show that noninvasively identifying the onset and propagation of interictal spike activity in MEG can be achieved, which may help provide further insight into epileptic networks and guide surgical planning and interventions in patients with TLE.

Failure of Surgery in Idiopathic Spinal Cord Herniation: Case Report and Review of the Literature.

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.

Betweenness centrality of intracranial electroencephalography networks and surgical epilepsy outcome.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. SIGNIFICANCE: This is the first study to identify network nodes that are possibly protective in epilepsy.

Intramedullary spinal epidermoid presenting after thoracic meningocele repair: case report.

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.

Revision surgery after interbody fusion with rhBMP-2: a cautionary tale for spine surgeons.

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.

Endonasal access to the upper cervical spine, part one: radiographic morphometric analysis.

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.

Epidemiological trends in the neurological intensive care unit from 2000 to 2008.

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<0.001) both significantly increased. Construction of a newer, larger Neuro-ICU at CUMC led to a substantial increase in admissions and changes in diagnoses from 2000 to 2008. Advances in neurocritical care, neurosurgical practices, and the local and global expansion and utilization of ICU resources likely led to differences in lengths of stay.

The surgical management of chronic subdural hematoma.

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.

Neurosurgical management of symptomatic thoracic spinal ossification in a patient with fibrodysplasia ossificans progressiva.

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.

Technological advances in the management of unruptured intracranial aneurysms fail to improve outcome in New York state.

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<0.0001) and increased in the case treatment rate for coiling of UIA (0.36 versus 1.98 per 100,000, P<0.0001). Compared with the old epoch, there were more UIAs clipped at high-volume centers (55.8% versus 78.8%, P<0.0001) but fewer coiled at high-volume centers (94.8% versus 84.5%, P<0.0001) in the new epoch. Coiling and increasing hospital UIA treatment volume were associated with good discharge outcome. However, there was no significant improvement in overall good outcome when comparing 1995 to 2000 versus 2005 to 2007 (79% versus 81%, 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.

Gain-of-function polymorphisms of cystathionine ß-synthase and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

OBJECT: Cystathionine ß-synthase (CBS) is an enzyme that metabolizes homocysteine to form H(2)S 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 H(2)S, 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 H(2)S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation.

Impact of platelet transfusion on hematoma expansion in patients receiving antiplatelet agents before intracerebral hemorrhage.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Epidemiology of aneurysmal subarachnoid hemorrhage.

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.

Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage.

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.

Genetic determinants of cerebral vasospasm, delayed cerebral ischemia, and outcome after aneurysmal subarachnoid hemorrhage.

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.

Data presentation in rodent stroke studies and the predictive value of confidence intervals.

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.

Intracranial infectious aneurysms: a comprehensive review.

Intracranial infectious aneurysms, or mycotic aneurysms, are rare infectious cerebrovascular lesions which arise through microbial infection of the cerebral arterial wall. Due to the rarity of these lesions, the variability in their clinical presentations, and the lack of population-based epidemiological data, there is no widely accepted management methodology. We undertook a comprehensive literature search using the OVID gateway of the MEDLINE database (1950-2009) using the following keywords (singly and in combination): "infectious," "mycotic," "cerebral aneurysm," and "intracranial aneurysm." We identified 27 published clinical series describing a total of 287 patients in the English literature that presented demographic and clinical data regarding presentation, treatment, and outcome of patients with mycotic aneurysms. We then synthesized the available data into a combined cohort to more closely estimate the true demographic and clinical characteristics of this disease. We follow by presenting a comprehensive review of mycotic aneurysms, highlighting current treatment paradigms. The literature supports the administration of antibiotics in conjunction with surgical or endovascular intervention depending on the character and location of the aneurysm, as well as the clinical status of the patient. Mycotic aneurysms comprise an important subtype of potentially life-threatening cerebrovascular lesions, and further prospective studies are warranted to define outcome following both conservative and surgical or endovascular treatment.

The influence of race on outcome following subarachnoid hemorrhage.

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 complement cascade as a therapeutic target in intracerebral hemorrhage.

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.