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Benjamin Davidson, Lior M. Elkaim, Nir Lipsman and George M. Ibrahim

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Laureen D. Hachem, Simeon M. Wong and George M. Ibrahim

Vagus nerve stimulation (VNS) is increasingly considered for the treatment of intractable epilepsy and holds potential for the management of a variety of neuropsychiatric conditions. The emergence of the field of connectomics and the introduction of large-scale modeling of neural networks has helped elucidate the underlying neurobiology of VNS, which may be variably expressed in patient populations and related to responsiveness to stimulation. In this report, the authors outline current data on the underlying neural circuitry believed to be implicated in VNS responsiveness in what the authors term the “vagus afferent network.” The emerging role of biomarkers to predict treatment effect is further discussed and important avenues for future work are highlighted.

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George M. Ibrahim, Aria Fallah and R. Loch Macdonald

Object

At present, the administration of prophylactic antiepileptic medication following aneurysmal subarachnoid hemorrhage (SAH) is controversial, and the practice is heterogeneous. Here, the authors sought to inform clinical decision making by identifying factors associated with the occurrence of seizures following aneurysm rupture.

Methods

Exploratory analysis was performed on 413 patients enrolled in CONSCIOUS-1 (Clazosentan to Overcome Neurological Ischemia and Infarction Occurring after Subarachnoid Hemorrhage), a prospective randomized trial of clazosentan for the prevention of angiographic vasospasm. The association among clinical, laboratory, and radiographic covariates and the occurrence of seizures following SAH were determined. Covariates with a significance level of p < 0.20 on univariate analysis were entered into a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was used to define optimal predictive thresholds.

Results

Of the 413 patients enrolled in the study, 57 (13.8%) had at least 1 seizure following SAH. On univariate analysis, a World Federation of Neurosurgical Societies grade of IV–V, a greater subarachnoid clot burden, and the presence of midline shift and subdural hematomas were associated with seizure activity. On multivariate analysis, only a subarachnoid clot burden (OR 2.76, 95% CI 1.39–5.49) and subdural hematoma (OR 5.67, 95% CI 1.56–20.57) were associated with seizures following SAH. Using ROC curve analysis, the optimal predictive cutoff for subarachnoid clot burden was determined to be 21 (of a possible 30) on the Hijdra scale (area under the curve 0.63).

Conclusions

A greater subarachnoid clot burden and subdural hematoma are associated with the occurrence of seizures after aneurysm rupture. These findings may help to identify patients at greatest risk for seizures and guide informed decisions regarding the prescription of prophylactic anticonvulsive therapy. Clinical trial registration no.: NCT00111085 (ClinicalTrials.gov).

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George M. Ibrahim, Stefan Weidauer and R. Loch Macdonald

Object

Numerous abnormal findings may be evident on CT scans after aneurysmal subarachnoid hemorrhage (SAH). Here, the authors assess the interobserver variability in the radiological interpretation of the initial CT scan following SAH.

Methods

Two experienced reviewers, a neurosurgeon and a neuroradiologist, independently prospectively reviewed the initial CT scans of 413 patients enrolled in the CONSCIOUS-1 trial. Measured variables included SAH, intraventricular hemorrhage, intracerebral hemorrhage, subdural hematoma, chronic infarction, midline shift, and hydrocephalus. To assess interobserver variability, weighted kappa values and intraclass correlation coefficients (ICCs) were calculated and Bland-Altman analysis was performed.

Results

Moderate to substantial agreement was found for most of the CT scanning findings. There was fair to moderate interobserver agreement between reviewers when determining the extent of SAH based on a descriptive categorical classification (kappa 0.41; 95% CI 0.33–0.49), and better agreement when a semiquantitative scale was used (ICC 0.56; 95% CI 0.49–0.62). There was poor agreement between reviewers for the presence of hydrocephalus (kappa 0.34; 95% CI 0.20–0.48), but substantial to near perfect agreement on ventriculocranial ratio measurements (ICC 0.77; 95% CI 0.72–0.81).

Conclusions

The authors' findings suggest that there is considerable interobserver variability in the interpretation of CT scans after SAH. Quantitative measures may reduce interobserver variability in comparison with qualitative or categorical scales. Variability in interpretation of CT scans has implications for patient care and conduct of clinical trials. It may be beneficial to develop standardized assessments to ensure consistent evaluation of measured variables.

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Eric C. Peterson and Roberto C. Heros

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Oliver G. S. Ayling, George M. Ibrahim, Brian Drake, James C. Torner and R. Loch Macdonald

OBJECT

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with substantial morbidity and mortality, with better outcomes reported following endovascular coiling compared with neurosurgical clipping of the aneurysm. The authors evaluated the contribution of perioperative complications and neurological decline to patient outcomes after both aneurysm-securing procedures.

METHODS

A post hoc analysis of perioperative complications from the Clazosentan to Overcome Neurological iSChemia and Infarction Occurring after Subarachnoid hemorrhage (CONSCIOUS-1) study was performed. Glasgow Coma Scale (GCS) scores for patients who underwent neurosurgical clipping and endovascular coiling were analyzed preoperatively and each day following the procedure. Complications associated with a decline in postoperative GCS scores were identified for both cohorts. Because patients were not randomized to the aneurysm-securing procedures, propensity-score matching was performed to balance selected covariates between the 2 cohorts. Using a multivariate logistic regression, the authors evaluated whether a perioperative decline in GCS scores was associated with long-term outcomes on the extended Glasgow Outcome Scale (eGOS).

RESULTS

Among all enrolled subjects, as well as the propensity-matched cohort, patients who underwent clipping had a significantly greater decline in their GCS scores postoperatively than patients who underwent coiling (p = 0.0024). Multivariate analysis revealed that intraoperative hypertension (p = 0.011) and intraoperative induction of hypotension (p = 0.0044) were associated with a decline in GCS scores for patients undergoing clipping. Perioperative thromboembolism was associated with postoperative GCS decline for patients undergoing coiling (p = 0.03). On multivariate logistic regression, postoperative neurological deterioration was strongly associated with a poor eGOS score at 3 months (OR 0.86, 95% CI 0.78-0.95, p = 0.0032).

CONCLUSIONS

Neurosurgical clipping following aSAH is associated with a greater perioperative decline in GCS scores than endovascular coiling, which is in turn associated with poorer long-term outcomes. These findings provide novel insight into putative mechanisms of improved outcomes following coiling, highlighting the potential importance of perioperative factors when comparing outcomes between clipping and coiling and the need to mitigate the morbidity of surgical strategies following aSAH.

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Taylor J. Abel, Emma Losito, George M. Ibrahim, Eishi Asano and James T. Rutka

Epileptic spasms (ES) are a common manifestation of intractable epilepsy in early life and can lead to devastating neurodevelopmental consequences. Epilepsy surgery for ES is challenging because of inherent difficulties in localizing the epileptogenic zone in affected infants and children. However, recent clinical series of resective neurosurgery for ES suggest that not only is surgery a viable option for appropriately selected patients, but postoperative seizure outcomes can be similar to those achieved in other types of focal epilepsy. Increased awareness of ES as a potentially focal epilepsy, along with advances in neuroimaging and invasive monitoring technologies, have led to the ability to surgically treat many patients with ES who were previously not considered surgical candidates. In this study, the authors review the current state of epilepsy surgery for ES. Specifically, they address how advances in neuroimaging and invasive monitoring have facilitated patient selection, presurgical evaluation, and ultimately, resection planning.

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Editorial

Spinal deformity

Michael G. Fehlings and George M. Ibrahim

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Daipayan Guha, George M. Ibrahim, Joshua D. Kertzer and R. Loch Macdonald

Object

Although heterogeneity exists in patient outcomes following subarachnoid hemorrhage (SAH) across different centers and countries, it is unclear which factors contribute to such disparities. In this study, the authors performed a post hoc analysis of a large international database to evaluate the association between a country's socioeconomic indicators and patient outcome following aneurysmal SAH.

Methods

An analysis was performed on a database of 3552 patients enrolled in studies of tirilazad mesylate for aneurysmal SAH from 1991 to 1997, which included 162 neurosurgical centers in North and Central America, Australia, Europe, and Africa. Two primary outcomes were assessed at 3 months after SAH: mortality and Glasgow Outcome Scale (GOS) score. The association between these outcomes, nation-level socioeconomic indicators (percapita gross domestic product [GDP], population-to-neurosurgeon ratio, and health care funding model), and patientlevel covariates were assessed using a hierarchical mixed-effects logistic regression analysis.

Results

Multiple previously identified patient-level covariates were significantly associated with increased mortality and worse neurological outcome, including age, intraventricular hemorrhage, and initial neurological grade. Among national-level covariates, higher per-capita GDP (p < 0.05) was associated with both reduced mortality and improved neurological outcome. A higher population-to-neurosurgeon ratio (p < 0.01), as well as fewer neurosurgical centers per population (p < 0.001), was also associated with better neurological outcome (p < 0.01). Health care funding model was not a significant predictor of either primary outcome.

Conclusions

Higher per-capita gross GDP and population-to-neurosurgeon ratio were associated with improved outcome after aneurysmal SAH. The former result may speak to the availability of resources, while the latter may be a reflection of better outcomes with centralized care. Although patient clinical and radiographic phenotypes remain the primary predictors of outcome, this study shows that national socioeconomic disparities also explain heterogeneity in outcomes following SAH.