[show abstract][hide abstract] ABSTRACT: The most deadly form of stroke, intracerebral hem-orrhage (ICH) continues to puzzle researchers and produce substantial decrements in the quality of patients' lives. Inten-sive basic research has devised many agents with putative benefit in mitigating the devastating effects of ICH, but these therapies have been largely ineffective in the transition to clinical trials. However, a steady translational pipeline contin-ues to provide new avenues of treatment that may be effective in the management of this condition. In this review, we aim to summarize the array of neuroprotective clinical trials and techniques used in the history of ICH, and delineate the progression of relevant research to date. Furthermore, we provide insight into methods that may allow for better trans-lation of basic science advances into productive clinical trials.
[show abstract][hide abstract] ABSTRACT: Intracerebral hemorrhage (ICH) is a devastating form of stroke associated with a high rate of morbidity and mortality. It is now believed that much of this damage occurs in the subacute period following the initial insult via a cascade of complex pathophysiologic pathways that continues to be investigated. Increased levels of certain serum proteins have been identified as biomarkers that may reflect or directly participate in the inflammation, blood brain barrier disruption, endothelial dysfunction, and neuronal and glial toxicity that occur during this secondary period of cerebral injury. Some of these biomarkers have the potential to serve as therapeutic targets or surrogate endpoints for future research or clinical trials. Others may someday augment current clinical techniques in diagnosis, risk-stratification, prognostication, treatment decision and measurement of therapeutic efficacy. While much work remains to be done, biomarkers show significant potential to expand clinical options and improve clinical management, thereby reducing mortality and improving functional outcomes in ICH patients.
Journal of the neurological sciences 08/2012; 321(1-2):1-10. · 2.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: The ICH score is a validated method of assessing the risk of mortality and morbidity after intracerebral hemorrhage (ICH). We sought to compare the ability of the ICH score to predict outcome assessed with three of the most widely used scales: the Barthel Index (BI), modified Rankin Scale (mRS), and Glasgow Outcome Score (GOS). All patients with ICH treated at our institution between February 2009 and March 2011 were followed-up at three months using the mRS, GOS, and BI. The ICH score was highly correlated with the three-month mRS (ρ=0.59, p<0.001), BI (ρ=-0.57, p<0.001) and GOS (ρ=0.61, p<0.001). The ICH score also predicted dependency for each measure well, with areas under the curve falling between 0.826 and 0.833. Our results suggest that future clinical studies that use the ICH score to stratify patients may employ any of the three outcome scales and expect good discrimination of disability.
Journal of Clinical Neuroscience 04/2012; 19(6):795-8. · 1.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Models employing peripheral nerve to bypass spinal cord injury (SCI), although highly promising, may benefit from improved nerve regeneration and motor bridge connectivity. Recent studies have demonstrated that neuronal growth factor-induced enhancement of endogenous neurorestoration may improve neuronal connectivity after severe neurologic injury, particularly if delivered intraparenchymally with zero-order kinetics. We sought to investigate the effect of convection-enhanced delivery of brain-derived neurotrophic factor (BDNF), a neuronal growth factor, on the connectivity of a peripheral motor-nerve bridge in a rodent model using electrophysiology and immunohistochemistry (IHC). Spinal cords of 29 female rats were hemisected at the L1 level. Ipsilateral T13 peripheral nerves were dissected from their muscular targets distally, while maintaining their connections with the spinal cord, and inserted caudal to the injury site to establish the nerve bridge. A microcannula attached to a six-week mini-osmotic pump was used to deliver either BDNF (n=12), saline (n=14), or fluorescein dye (n=3) directly into the spinal cord parenchyma between the site of nerve insertion and hemisection to a depth of 2mm into the area of the lateral motor pool. After four weeks, gastrocnemius muscle activation was assessed electromyographically in five animals from each group. Spinal cords were harvested and analyzed with IHC for cannula-associated injury, and nerve regeneration. Strength of motor bridge connection was illustrated by electrophysiology data. Intraspinal BDNF levels were measured using enzyme-linked immunosorbent assay. IHC revealed increased intraparenchymal BDNF concentration at the nerve bridge insertion site with evidence of minimal trauma from cannulation. BDNF infusion resulted in stronger connections between bridge nerves and spinal motor axons. Bridge nerve electrical stimulation in BDNF-treated rats evoked hind leg electromyogram responses of shorter latency and larger amplitudes than saline-infused controls. Thus, direct convection-assisted delivery provides reliable administration of potent growth factors directly into the spinal cord parenchyma. Delivery of BDNF at the peripheral nerve bridge site results in enhanced connectivity of the peripheral motor bridge in a rodent model of SCI.
Journal of Clinical Neuroscience 04/2012; 19(4):563-9. · 1.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Alteration in platelet aggregation has been shown to promote bleeding and affect outcome after intracerebral hemorrhage (ICH).We investigated the influence of genetic variants of platelet aggregation, and their effects on admission ICH volume and clinical outcome.
Our prospective study analyzed selected candidate single-nucleotide polymorphisms (SNPs) previously associated with platelet aggregation phenotype in previous genome-wide association studies, with regards to outcome and ICH volume. Patients were assessed at the Columbia University Medical Center Neuro-Intensive Care Unit. Exclusion criteria included age <18 years, ICH following trauma, hemorrhagic transformation, or tumor, no consent for genetic analysis, or incomplete data. Radiological variables (location and volume of acute ICH, presence of intraventricular extension, midline shift, and hydrocephalus) and clinical variables (mortality and modified Rankin score at discharge) were prospectively recorded.
One hundred and twenty-two patients with spontaneous ICH between February 2009 and May 2011 diagnosed via clinical assessment and admission computed tomography scan were included. The median admission Glasgow coma scale score (GCS) was 11·5. Univariate predictors of mortality at discharge included systolic blood pressure, presence of intraventricular hemorrhage, anticoagulant use, and GCS, the only independent predictor of discharge mortality (P<0·001). Age, intraventricular hemorrhage, and GCS were associated with poor functional outcome; age (P = 0·001) and GCS (P<0·001) were significant in the multivariate model. Admission GCS (P<0·01), antiplatelet use, and rs342286 (PIK3CG; P = 0·04; R(2) = 0·247) had univariate associations with hematoma volume.
We identified SNP rs342286 as an independent predictor of admission hematoma volume. Our findings suggest that PIK3CG function, which is previously linked to this SNP and affects platelet aggregation, impacts the severity of the intraparenchymal bleed.
Neurological Research 03/2012; 34(3):232-7. · 1.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Hematoma expansion, the leading cause of neurologic deterioration after intracerebral hemorrhage (ICH), remains one of the few modifiable risk factors for poor outcome. In the present study, we explored whether common genetic variants within the hemostasis pathway were related to hematoma expansion during the acute period after ICH. METHODS: Patients with spontaneous ICH who were admitted to the institutional Neuro-ICU between 2009 and 2011 were enrolled in the study, and clinical data were collected prospectively. Hematoma size was measured in patients admitted on or before postbleed day 2. Baseline models for hematoma growth were constructed using backwards stepwise logistic regression. Genotyping of single-nucleotide polymorphisms for 13 genes involved in hemostasis was performed, and the results were individually included in the above baseline models to test for independent association of hematoma expansion. RESULTS: During the study period, 82 patients were enrolled in the study and had complete data. The mean age was 65.9 ± 14.9 years, and 38% were female. Only von Willebrand factor was associated with absolute and relative hematoma growth in univariate analysis (P < .001 and P = .007, respectively); von Willebrand factor genotype was independently predictive of relative hematoma growth but only approached significance for absolute hematoma growth (P = .002 and P = .097, respectively). CONCLUSIONS: Our genomic analysis of various hemostatic factors identified von Willebrand factor as a potential predictor of hematoma expansion in patients with ICH. The identification of von Willebrand factor single-nucleotide polymorphisms may allow us to better identify patients who are at risk for hematoma enlargement and will benefit the most from treatment. The relationship of von Willebrand factor with regard to hematoma enlargement in a larger population warrants further study.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 01/2012;
[show abstract][hide abstract] ABSTRACT: Intraventricular hemorrhage (IVH) associated with intracerebral hemorrhage (ICH) is an independent predictor of poor outcome. Clinical methods for evaluating IVH, however, are not well established. This study sought to determine the best IVH grading scale by evaluating the predictive accuracies of IVH, Graeb, and LeRoux scores in an independent cohort of ICH patients with IVH. Subacute IVH dynamics as well as the impact of external ventricular drain (EVD) placement on IVH and outcome were also investigated.
A consecutive cohort of 142 primary ICH patients with IVH was admitted to Columbia University Medical Center between February 2009 and February 2011. Baseline demographics, clinical presentation, and hospital course were prospectively recorded. Admission CT scans performed within 24 hours of onset were reviewed for ICH location, hematoma volume, and presence of IVH. Intraventricular hemorrhage was categorized according to IVH, Graeb, and LeRoux scores. For each patient, the last scan performed within 6 days of ictus was similarly evaluated. Outcomes at discharge were assessed using the modified Rankin Scale (mRS). Receiver operating characteristic analysis was used to determine the predictive accuracies of the grading scales for poor outcome (mRS score ≥ 3).
Seventy-three primary ICH patients (51%) had IVH. Median admission IVH, Graeb, and LeRoux scores were 13, 6, and 8, respectively. Median IVH, Graeb and LeRoux scores decreased to 9 (p = 0.005), 4 (p = 0.002), and 4 (p = 0.003), respectively, within 6 days of ictus. Poor outcome was noted in 55 patients (75%). Areas under the receiver operating characteristic curve were similar among the IVH, Graeb, and LeRoux scores (0.745, 0.743, and 0.744, respectively) and within 6 days postictus (0.765, 0.722, 0.723, respectively). Moreover, the IVH, Graeb, and LeRoux scores had similar maximum Youden Indices both at admission (0.515 vs 0.477 vs 0.440, respectively) and within 6 days postictus (0.515 vs 0.339 vs 0.365, respectively). Patients who received EVDs had higher mean IVH volumes (23 ± 26 ml vs 9 ± 11 ml, p = 0.003) and increased incidence of Glasgow Coma Scale scores < 8 (67% vs 38%, p = 0.015) and hydrocephalus (82% vs 50%, p = 0.004) at admission but had similar outcome as those who did not receive an EVD.
The IVH, Graeb, and LeRoux scores predict outcome well with similarly good accuracy in ICH patients with IVH when assessed at admission and within 6 days after hemorrhage. Therefore, any of one of the scores would be equally useful for assessing IVH severity and risk-stratifying ICH patients with regard to outcome. These results suggest that EVD placement may be beneficial for patients with severe IVH, who have particularly poor prognosis at admission, but a randomized clinical trial is needed to conclusively demonstrate its therapeutic value.
Journal of Neurosurgery 01/2012; 116(1):185-92. · 3.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: Central fever is common after aneurysmal subarachnoid hemorrhage (aSAH) and may delay ventriculoperitoneal shunt (VPS) placement.
We hypothesize that drain-dependent aSAH patients with central fever or persistent fever after treatment of an identifiable cause are not at an increased risk of infectious VPS failure.
Patient demographics, radiographic characteristics, temperature, incidence of infection, and shunt failure were prospectively recorded in a consecutive cohort of aSAH patients. Central fever was defined as temperature higher than 38.3°C with no identifiable cause.
Of 580 patients, 61 (11%) were drain dependent. Central fever developed in 18, 35 had fever of known etiology, and 8 remained afebrile. There was no shunt failure at discharge, and 2 failures (3.2%) at follow-up were attributed to infection. One patient with central fever (6%), none with fever of identifiable etiology, and 1 (13%) with no fever had infectious shunt failures at a median follow-up of 10.2 ± 3.6 months (P > .05). Nine patients with central fever (50%) and 6 (17%) who were treated for fever of known etiologies had persistent fever at shunt placement. Patients who were febrile on the day of surgery had similar infectious shunt failure rates at discharge compared with those who were afebrile (0% vs 0%; P = 1.0). Similarly, febrile and afebrile patients at VPS insertion had comparable rates of infectious shunt failure at follow-up (7% vs 2%; P = .43).
aSAH patients with central fever or persistent fever after treatment of fever of identifiable etiology are not at an increased risk of infectious VPS failure.
[show abstract][hide abstract] ABSTRACT: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour, with few available therapies providing significant improvements in mortality. Biomarkers, which are defined by the National Institutes of Health as 'characteristics that are objectively measured and evaluated as indicators of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention', have the potential to play valuable roles in the diagnosis and treatment of GBM. Although GBM biomarker research is still in its early stages because of the tumour's complex pathophysiology, a number of potential markers have been identified which can be measured in either brain tissue or blood serum. In conjunction with other clinical data, particularly neuroimaging modalities such as MRI, these proteins could contribute to the clinical management of GBM by helping to classify tumours, predict prognosis and assess treatment response. In this article, we review the current understanding of GBM pathophysiology and recent advances in GBM biomarker research, and discuss the potential clinical implications of promising biomarkers. A better understanding of GBM pathophysiology will allow researchers and clinicians to identify optimal biomarkers and methods of interpretation, leading to advances in tumour classification, prognosis prediction and treatment assessment.
British Journal of Neurosurgery 12/2011; 26(2):189-94. · 0.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: To evaluate the predictive ability of the original ICH Score (oICH) in a large independent cohort of patients with arteriovenous malformation-associated intracerebral hemorrhage (AVM-ICH), an important cause of intracerebral hemorrhage (ICH) that is associated with significantly different epidemiology, clinical course, and outcome compared with primary ICH. METHODS: During the period 1997-2009, 91 patients were admitted to Columbia Medical Center with acute AVM-ICH. Demographic and admission clinical and radiographic variables were obtained for 84 patients through retrospective chart review. Admission oICH and Spetzler-Martin grading scale (SMGS) were calculated. Outcome was assessed at 3 months using the modified Rankin Scale (mRS). Maximum Youden Indices were used to identify cutoffs for age and ICH volume that are associated with optimal predictive accuracy for an unfavorable outcome (mRS ≥ 3). Receiver operating characteristic (ROC) analysis was used to evaluate the predictive performance of oICH, and oICH with new age and ICH cutoff points (new AVM-ICH score based on original ICH Score [AVM-oICH]). RESULTS: The mean age was 35 years ± 14, and mean ICH volume was 22 mL ± 20. At 3-month follow-up, 3 (4%) patients were dead, and 15 (18%) had an unfavorable outcome. Two of the patients who died had oICH of 3, and one had oICH of 5. ICH volume of 37 mL and age of 41 years were identified as optimal cutoffs for predicting an unfavorable outcome. oICH and AVM-oICH showed good predictive accuracies with area under the curve of 0.914 and 0.891 (P = 0.422). AVM-oICH and oICH had similarly high sensitivities (0.889 and 0.944; P = 1.00), but the former had significantly greater specificity (0.879 vs. 0.682; P < 0.001). CONCLUSIONS: oICH is a valid clinical grading scale with high predictive accuracy for functional outcome after AVM-ICH. It is unclear whether the score is appropriate for risk stratification with regard to mortality because of the low risk of death associated with AVM-ICH. Simple adjustments of the age and ICH volume cutoff points improve performance of the score and reduce the probability of overestimating a patient's risk of an unfavorable outcome after AVM-ICH.
[show abstract][hide abstract] ABSTRACT: The role of the complement cascade in the pathophysiology of cerebral arteriovenous malformation (AVM) is largely undefined. Complement subcomponents, C3a and C5a, are potent anaphylatoxins and key mediators of immuno-inflammatory response. Complement activation may contribute to the pro-inflammatory state observed in AVM. Thus, we sought to determine the systemic levels of C3a and C5a and their response to treatments in patients with AVM. Blood samples of 18 patients undergoing treatment for unruptured AVM, and from 30 healthy control participants, were obtained at four times: (i) pre-treatment, (ii) 24-hours post-embolization, (iii) 24-hours post-resection, and at 1-month follow-up. Plasma concentrations of C3a and C5a were measured using enzyme-linked immunosorbent assay. The pre-treatment mean plasma C3a level was significantly higher in patients with AVM (1817±168 ng/mL) compared to controls (1126±151 ng/mL). The mean C3a level decreased 24-hours after embolization (1482±170 ng/mL) and remained at statistically similar levels 24-hours after resection (1511±149 ng/mL) and at 1-month follow-up (1535±133 ng/mL). Mean C3a levels at the three time points were higher than control levels.The baseline mean plasma C5a level was significantly elevated in patients with AVM (13.1±2.2 ng/mL) compared to controls (3.9±1.5 ng/mL).Mean C5a level decreasedpost-embolization (8.2±2.3 ng/mL) and remained at similar levels post-resection (8.5±3.0 ng/mL) and at 1-month follow-up (7.7±2.9 ng/mL). Mean C5a levels at the three time points were significantly higher than the control levels. We conclude that systemic C3a and C5a levels in patients with AVM are elevated at baseline, decrease significantly after embolization, and remain at the new baseline levels after surgery and 1-month follow-up.
Journal of Clinical Neuroscience 09/2011; 18(9):1235-9. · 1.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intracerebral hemorrhage (ICH) accounts for 10% to 15% of all strokes and is a major cause of morbidity and mortality. Despite advances in management, numerous clinical trials have failed to demonstrate significant benefit of medical and surgical interventions, underscoring the need for the identification of novel therapeutic targets based on improved understanding of ICH pathophysiology and optimal risk stratification based on reliable and effective prognosticators. The alternative complement cascade has been implicated as an important contributor to neurological injury after ICH. Therefore, common, functionally relevant genetic variants in the key components of this pathway have been associated with greater inflammation post-ictus, further cerebral damage, and ultimately, a worse outcome. We investigated the affects of single-nucleotide polymorphisms (SNP) on mortality in complement component 3 C3 (rs2230199), complement component 5 C5 (rs17611), and Complement Factor H (CFH; rs1061170) genes, which are associated with the onset and progression of several neurological diseases, in a prospective cohort of patients with spontaneous ICH. From February 2009 through May 2010, adult patients with spontaneous ICH were admitted to the Columbia University Neurological Intensive Care Unit and enrolled in the Intracerebral Hemorrhage Outcomes Project. Demographic, clinical, radiographic, and treatment data were prospectively collected. Buccal swabs were obtained, and isolated cells were sequenced for the aforementioned SNP. A total of 103 patients were admitted with ICH, and of these, 82 consented for genetic testing and were included in the analysis. The median age was 61 years and 39% were females. The median Glasgow Coma Scale score on admission was 11.5. The CFH SNP was significantly associated with both discharge (p = 0.01) and 6-month mortality (p = 0.02), while no such association was observed for C3 (p = 0.545 and p = 0.830) or C5 (p = 0.983 and p = 0.536) SNP. Additionally, after controlling for pertinent variables identified in the univariate analysis, the CFH genotype independently predicted mortality at discharge (p = 0.019, odds ratio [OR] 7.62, 95% confidence interval [CI] 1.40-41.6) and at 6 months (p = 0.041, OR 1.822, 95% CI 1.025-3.239). The CFH genotype was also independently predictive of survival duration (p = 0.041, OR 1.822, 95% CI 1.025-3.239). We concluded that CFH Y402H polymorphism independently predicts mortality at discharge and 6-months and survival duration after spontaneous ICH.
Journal of Clinical Neuroscience 08/2011; 18(11):1439-43. · 1.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hyperglycemia after spontaneous intracerebral hemorrhage (ICH) is associated with poor outcome, but the pathophysiology of ICH-induced glucose dysregulation remains unclear. We sought to identify clinical and radiographic parameters of ICH that are associated with admission hyperglycemia.
Patients admitted to the Columbia University Medical Center Neurological Intensive Care Unit with spontaneous ICH between January 2009 and September 2010 were prospectively enrolled in the ICH Outcomes Project. Clinical, radiographic, and laboratory data were collected prospectively. Receiver operating characteristic analysis was used to identify the glucose level with optimal sensitivity and specificity for in-hospital mortality. Logistic and linear regression analyses were used to identify independent predictors of outcome measures where appropriate.
One hundred four patients admitted during the study period were included in the analysis. Mean admission glucose level was 8.23 ± 3.15 mmol/L (3.83 to 18.89 mmol/L) and 23.2% had a history of diabetes mellitus. Admission glucose was significantly associated with discharge (P=0.003) and 3-month mortality (P=0.002). Critical hyperglycemia defined at 10 mmol/L independently predicted discharge mortality (P=0.027; OR, 4.381; 95% CI, 1.186 to 16.174) and 3-month mortality (P=0.011; OR, 10.95; 95% CI, 1.886 to 62.41). Admission intraventricular extension score (P=0.038; OR, 1.117; 95% CI, 1.043 to 1.197) and diabetes mellitus (P=0.002; OR, 5.530; 95% CI, 1.833 to 16.689) were independent predictors of critical hyperglycemia. The intraventricular extension score (B=0.115, P=0.001) linearly correlated with admission glucose level (R=0.612, P=0.001) after adjusting for other clinical variables.
Admission hyperglycemia after spontaneous ICH is associated with poor outcome and potentially related to the presence and severity of intraventricular extension.
[show abstract][hide abstract] ABSTRACT: Outcome after intraarterial therapy (IAT) for acute ischemic stroke remains variable, suggesting that improved patient selection is needed to better identify patients likely to benefit from treatment. The authors evaluate the predictive accuracies of the Houston IAT (HIAT) and the Totaled Health Risks in Vascular Events (THRIVE) scores in an independent cohort and review the existing literature detailing additional predictive factors to be used in patient selection for IAT. They reviewed their center's endovascular records from January 2004 to July 2010 and identified patients who had acute ischemic stroke and underwent IAT. They calculated individual HIAT and THRIVE scores using patient age, admission National Institutes of Health Stroke Scale (NIHSS) score, admission glucose level, and medical history. The scores' predictive accuracies for good outcome (discharge modified Rankin Scale score ≤ 3) were analyzed using receiver operating characteristics analysis. The THRIVE score predicts poor outcome after IAT with reasonable accuracy and may perform better than the HIAT score. Nevertheless, both measures may have significant clinical utility; further validation in larger cohorts that accounts for differences in patient demographic characteristics, variation in time-to-treatment, and center preferences with respect to IAT modalities is needed. Additional patient predictive factors have been reported but not yet incorporated into predictive scales; the authors suggest the need for additional data analysis to determine the independent predictive value of patient admission NIHSS score, age, admission hyperglycemia, patient comorbidities, thrombus burden, collateral flow, time to treatment, and baseline neuroimaging findings.
[show abstract][hide abstract] ABSTRACT: Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFH Y402H) genes on incidence of neurocognitive dysfunction post-CEA.
This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery.
57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFH Y402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F- subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively).
The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery.
Journal of neurology, neurosurgery, and psychiatry 03/2011; 82(3):247-53. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: In recent years, a multitude of clinical grading scales have been created to help identify patients at greater risk of poor outcome following ICH. We sought to validate and compare eight of the most frequently used ICH grading scales in a prospective cohort.
Eight grading scales were calculated for 67 patients with non-traumatic ICH enrolled in the prospective intracerebral hemorrhage outcomes project (ICHOP) database. Receiver operating characteristic (ROC) analysis, including area under the curve (AUC) and maximum Youden Index were used to assess the ability of each score to predict in-hospital mortality, long-term (3 months) mortality, and functional outcome at 3 months (mRS ≥ 3).
All scales demonstrated excellent to outstanding discrimination for in-hospital and long-term mortality, with no significant differences between them after controlling for the false discovery rate. All scales demonstrated acceptable to outstanding discrimination for functional outcome at 3 months, with the new ICH score demonstrating significantly lower AUC than 6 of the 8 scores. Essen ICH score was the only score to demonstrate outstanding discrimination for each outcome measure.
Though significant differences were minimal in our cohort, we showed the existing selection of ICH grading scales to be useful in stratifying patients according to risk of mortality and poor functional outcome. Continued validation and comparison in large prospective cohorts will bring the goal of a singular prognostic model for ICH closer to fruition.
Neurocritical Care 03/2011; 15(3):498-505. · 3.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intracerebral hemorrhage (ICH) is associated with higher mortality and morbidity than any other form of stroke. However, there currently are no treatments proven to improve outcomes after ICH, and therefore, new effective therapies are urgently needed. Growing insight into ICH pathophysiology has led to the development of neuroprotective strategies that aim to improve the outcome through reduction of secondary pathologic processes. Many neuroprotectants target molecules or pathways involved in hematoma degradation, inflammation or apoptosis, and have demonstrated potential clinical benefits in experimental settings. We extensively reviewed the current understanding of ICH pathophysiology as well as promising experimental neuroprotective agents with particular focus on their mechanisms of action. Continued advances in ICH knowledge, increased understanding of neuroprotective mechanisms, and improvement in the ability to modulate molecular and pathologic events with multitargeting agents will lead to successful clinical trials and bench-to-bedside translation of neuroprotective strategies.
[show abstract][hide abstract] ABSTRACT: Exposure to isoflurane gas prior to neurological injury, known as anesthetic preconditioning, has been shown to provide neuroprotective benefits in animal models of ischemic stroke. Given the common mediators of cellular injury in ischemic and hemorrhagic stroke, we hypothesize that isoflurane preconditioning will provide neurological protection in intracerebral hemorrhage (ICH).
24 h prior to intracerebral hemorrhage, C57BL/6J mice were preconditioned with a 4-h exposure to 1% isoflurane gas or room air. Intracerebral hemorrhage was performed using a double infusion of 30-μL autologous whole blood. Neurological function was evaluated at 24, 48 and 72 h using the 28-point test. Mice were sacrificed at 72 h, and brain edema was measured.
Mice preconditioned with isoflurane performed better than control mice on 28-point testing at 24 h, but not at 48 or 72 h. There was no significant difference in ipsilateral hemispheric edema between mice preconditioned with isoflurane and control mice.
These results demonstrate the early functional neuroprotective effects of anesthetic preconditioning in ICH and suggest that methods of preconditioning that afford protection in ischemia may also provide protection in ICH.
[show abstract][hide abstract] ABSTRACT: External ventricular drain (EVD) placement is standard of care in the management of aneurysmal subarachnoid haemorrhage-associated hydrocephalus (aSAH). However, there are no guidelines for EVD placement and management after aSAH. Optimal EVD insertion conditions, techniques to reduce the risk of EVD-associated infection and aneurysmal rebleeding, and methods of EVD removal are critical, yet incompletely answered management variables. The present literature consists primarily of small studies with heterogeneous populations and variable outcome measures, and suggests the following: EVDs may increase the risk of rebleeding; EVDs are increasingly placed by non-neurosurgeons with unclear results; intraparenchymal ICP monitors may be safely considered (with or without spinal drainage) in the setting of difficult EVD placement; the optimal timing and manner of EVD removal has yet to be defined; and the efficacy of prophylactic systemic antibiotics and antibiotic-coated EVDs needs further investigation. Nevertheless, there are no definitive practice guidelines for EVD placement and management techniques in aSAH patients. Large prospective randomised trials are needed to definitively address important gaps in our understanding of EVD management principles in the neurocritical care setting.
British Journal of Neurosurgery 12/2010; 24(6):625-32. · 0.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this report, the evidence, mechanisms, and rationale for the practice of artificial cranial deformation (ACD) in ancient Peru and during Akhenaten's reign in the 18th dynasty in Egypt (1375-1358 BCE) are reviewed. The authors argue that insufficient attention has been given to the sociopolitical implications of the practice in both regions. While evidence from ancient Peru is widespread and complex, there are comparatively fewer examples of deformed crania from the period of Akhenaten's rule. Nevertheless, Akhenaten's own deformity, the skull of the so-called "Younger Lady" mummy, and Tutankhamen's skull all evince some degree of plagiocephaly, suggesting the need for further research using evidence from depictions of the royal family in reliefs and busts. Following the anthropological review, a neurosurgical focus is directed to instances of plagiocephaly in modern medicine, with special attention to the conditions' etiology, consequences, and treatment. Novel clinical studies on varying modes of treatment will also be studied, together forming a comprehensive review of ACD, both in the past and present.