Gustavo Pradilla

Role of inflammation (leukocyte-endothelial cell interactions) in vasospasm after subarachnoid hemorrhage.

BACKGROUNDnDelayed vasospasm is the leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). This phenomenon was first described more than 50 years ago, but only recently has the role of inflammation in this condition become better understood.nnnMETHODSnThe literature was reviewed for studies on delayed vasospasm and inflammation.nnnRESULTSnThere is increasing evidence that inflammation and, more specifically, leukocyte-endothelial cell interactions play a critical role in the pathogenesis of vasospasm after aSAH, as well as in other conditions including meningitis and traumatic brain injury. Although earlier clinical observations and indirect experimental evidence suggested an association between inflammation and chronic vasospasm, recently direct molecular evidence demonstrates the central role of leukocyte-endothelial cell interactions in the development of chronic vasospasm. This evidence shows in both clinical and experimental studies that cell adhesion molecules (CAMs) are up-regulated in the perivasospasm period. Moreover, the use of monoclonal antibodies against these CAMs, as well as drugs that decrease the expression of CAMs, decreases vasospasm in experimental studies. It also appears that certain individuals are genetically predisposed to a severe inflammatory response after aSAH based on their haptoglobin genotype, which in turn predisposes them to develop clinically symptomatic vasospasm.nnnCONCLUSIONnBased on this evidence, leukocyte-endothelial cell interactions appear to be the root cause of chronic vasospasm. This hypothesis predicts many surprising features of vasospasm and explains apparently unrelated phenomena observed in aSAH patients. Therapies aimed at preventing inflammation may prevent and/or reverse arterial narrowing in patients with aSAH and result in improved outcomes.

Epidural abscesses of the CNS

Epidural abcessess can involve the intercranial or spinal compartments and can result in potentially devastating neurological injuries. Although rare, incidence of spinal epidural abscesses (SEAs) is increasing as predisposing factors such as injected-drug use, chronic immunosuppression, and spinal surgery become more common. Whereas symptoms of SEAs can include fever, back pain, and neurological dysfunction, the presentation of intracranial epidural abscesses (ICEAs) is less well defined. Neuroimaging narrows the potential diagnoses and enables prompt empirical therapy until specific microbiological diagnosis is made. Surgical intervention is an integral part of treatment for epidural abscesses in patients with neurological symptoms or who have not responded to medical management. Prognosis for both SEAs and ICEAs is typically poor because of delayed diagnosis and intervention and is dependent on the neurological status at the time of diagnosis. Increased clinical awareness can greatly improve outcomes by helping to diagnose patients earlier.

Inflammation and Cerebral Vasospasm After Subarachnoid Hemorrhage

Morbidity and mortality of patients with aneurysmal subarachnoid hemorrhage (aSAH) is significantly related to the development of chronic cerebral vasospasm. Despite extensive clinical and experimental research, the pathophysiology of the events that result in delayed arterial spasm is not fully understood. A review of the published literature on cerebral vasospasm that included but was not limited to all PubMed citations from 1951 to the present was performed. The findings suggest that leukocyte-endothelial cell interactions play a significant role in the pathophysiology of cerebral vasospasm and explain the clinical variability and time course of the disease. Experimental therapeutic targeting of the inflammatory response when timed correctly can prevent vasospasm, and supplementation of endothelial relaxation by nitric oxide-related therapies and other approaches could result in reversal of the arterial narrowing and improved outcomes in patients with aSAH.

Intra-Aortic Balloon Pump Counterpulsation in the Setting of Subarachnoid Hemorrhage, Cerebral Vasospasm, and Neurogenic Stress Cardiomyopathy. Case Report and Review of the Literature

BackgroundThe management of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) can be often complicated by the presence of stunned myocardium and left ventricular failure. Vasopressors and inotropes are commonly used to optimize mean arterial pressure (MAP) and cerebral perfusion pressure (CPP). Intra-aortic balloon counterpulsation pump (IABP) may be indicated in the management of these patients.MethodsWe report the case of a 55-year-old patient who suffered an aSAH complicated by severe left ventricular failure, who subsequently developed symptomatic cerebral vasospasm. Left ventricular failure precluded traditional hemodynamic augmentation, and IABP was successfully used instead, which allowed for reinstitution of hypertensive hypervolemic therapy and prevented delayed cerebral ischemia.ResultsA review of the literature conducted on symptomatic cerebral vasospasm after aSAH and severe left ventricular failure revealed seven publications describing 14 patients with aSAH treated with an IABP during the period of vasospasm.ConclusionsIntra-aortic balloon counterpulsation pump (IABP) is used for hemodynamic support of patients in cardiogenic shock and its use in the setting of aSAH, cardiomyopathy, and cerebral vasospasm can be beneficial in preventing delayed ischemic deficits.

Local Delivery of Minocycline and Systemic BCNU have Synergistic Activity in the Treatment of Intracranial Glioma

Minocycline, a tetracycline derivative, has been shown to inhibit tumor angiogenesis through inhibitory effects on matrix metalloproteinases. Previous studies have shown this agent to be effective against a rodent brain tumor model when delivered intracranially and to potentiate the efficacy of standard chemotherapeutic agents. In the present study, the in vivo efficacy of intracranial minocycline delivered by a biodegradable controlled-release polymer against rat intracranial 9L gliosarcoma was investigated to determine whether it potentiates the effects of systemic 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). Minocycline was incorporated into the biodegradable polymer polyanhydride poly[bis(p-carboxyphenoxy)propane-sebacic acid] (pCPP:SA) at a ratio of 50:50 by weight. The release kinetics of minocycline from the polymer were assessed. For the efficacy studies, female Fischer 344 rats were implanted with 9L glioma. Treatment with minocycline delivered by the pCPP:SA polymer at the time of tumor implantation resulted in 100% survival in contrast to untreated control animals that died within 21 days. Treatment with the minocycline-polymer 5 days after tumor implantation provided only modest increases in survival. The combination of intracranial minocycline and systemic BCNU extended median survival by 82% compared to BCNU alone (p < 0.0001) and 200% compared to no treatment (p < 0.004). We conclude that local intracranial delivery of minocycline from biodegradable controlled-release polymers inhibits tumor growth and may have clinical utility when combined with a chemotherapeutic agent.

Spinal Epidural Abscess: Current Diagnosis and Management

Spinal epidural abscess (SEA) is an uncommon condition that warrants urgent diagnosis and treatment, because early pharmacotherapy significantly improves prognosis and prompt surgical decompression is often necessary to prevent or minimize neurologic complications. Increased awareness is critical; any of the characteristic clinical findings, especially in the presence of risk factors and elevated inflammatory markers, should lead to heightened suspicion for SEAs and its consideration on differential diagnosis, even in the absence of neurologic deficits. A multidisciplinary approach is essential for successful management of SEAs; along with infectious disease specialists and neurosurgeons/orthopedic spine surgeons, primary care, emergency medicine, and internal medicine clinicians are more likely to see patients with SEAs at earlier stages and play a pivotal role in early diagnosis and treatment. A combination of targeted antibiotic therapy and prompt surgical decompression is recommended in most cases, although medical management alone can be effective in select patients under close monitoring.

Solitary thoracic osteochondroma: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Osteochondromas are common benign bone tumors that rarely arise in the vertebral column. Intraspinal presentation of these tumors is usually circumscribed to the cervical regions with few tumors presenting in the thoracic vertebrae. We report a case of a thoracic solitary osteochondroma arising from within the vertebral body, review the cases reported in the literature, and propose recommendations for the surgical management of these challenging lesions. CLINICAL PRESENTATION: A 26-year-old woman presented with clinical signs of spinal cord compression consisting of right lower extremity weakness and left lower extremity numbness. Magnetic resonance imaging showed a small enhancing epidural mass behind the vertebral body of T12. INTERVENTION: A T12 corpectomy was performed with thoracolumbar fixation and fusion. CONCLUSION: Our case is atypical in that the tumor arose from the posterior portion of the T12 body, causing spinal cord dysfunction that necessitated an anterior approach to T12 for corpectomy with thoracolumbar fixation and fusion. Surgical intervention was effective in completely resolving the patients right lower extremity weakness.

Accuracy of computed tomography angiography in the diagnosis of intracranial aneurysms.

OBJECTIVEnAlthough digital subtraction angiography (DSA) remains the standard for intracranial aneurysm diagnosis, computed tomography angiography (CTA) is being increasingly used for this purpose. CTA has sensitivities and specificities reported as high as 97% and 100%, respectively. We analyzed a prospective cohort of 112 patients with 134 unruptured aneurysms who underwent community CTAs and confirmatory DSAs in a tertiary facility.nnnMETHODSnPatients referred between 2007 and 2010 (mean age 53.2 years) with aneurysms identified by CTA underwent confirmatory DSA. The results were compared to determine accuracy of CTA in diagnosing aneurysms. Aneurysms diagnosed by CTA but ruled out by DSA or aneurysms missed by CTA but diagnosed by DSA were analyzed by size and location. Anatomical variants leading to false CTA positive results were noted.nnnRESULTSnCTA identified 132 aneurysms, of which 27 (20.5%) were false positives. Of these 27 aneurysms, 18 were completely negative but 9 had an anatomical structure that explained the CTA finding, 18 were either small (6-10 mm, 4%) or very small (1-5 mm, 63%), and 16 were located either in the anterior communicating artery (ACoA) region (33%) or at the basilar artery bifurcation (26%). Additionally, DSA identified 29 aneurysms (21.6%) missed by CTA. The most common locations for these were the cavernous segment of the internal carotid artery (24%) and the middle cerebral artery (24%), and all but 1 were very small (1-5 mm).nnnCONCLUSIONnThe CTA accuracy rate may be lower than previously reported. CTA is particularly inaccurate in aneurysms 5 mm or smaller and those in the ACoA region.

Surgical Treatment of Cranial Arteriovenous Malformations and Dural Arteriovenous Fistulas

Microsurgical resection remains the treatment of choice for more than half of all patients with arteriovenous malformations (AVMs). It reduces the treatment window to a span of a few weeks and is curative. Careful patient selection, meticulous surgical planning, and painstaking technical execution of surgery are typically rewarded with excellent outcomes. For dural arteriovenous fistulas (DAVFs), microsurgical obliteration is often reserved for cases in which endovascular therapy either cannot be pursued or fails. When performed, however, microsurgical obliteration of DAVFs is associated with excellent outcomes as well. This article reviews the current state of microsurgical treatment of AVMs and DAVFs.

Surgical considerations of spinal ependymomas in the pediatric population

ObjectivesThe objective of this manuscript is to discuss current management strategies regarding pediatric patients with intramedullary spinal cord ependymomas. Spinal ependymoma is the second most common spinal cord tumor in children. The clinical evaluation of these patients, operative techniques, postoperative management considerations, and long-term outcomes are discussed.IntroductionThe gold standard for the treatment of spinal ependymoma continues to be gross total resection. Patients with residual tumor postoperatively may benefit from adjuvant radiation therapy. Intraoperative monitoring is critical to minimize permanent postoperative neurologic deficit.ConclusionPatients requiring multilevel laminectomy may benefit from concomitant laminoplasty or instrumented fusion to avoid progressive spinal column deformity.