Eric S. Nussbaum

Reperfusion injury after focal cerebral ischemia: The role of inflammation and the therapeutic horizon

Recent evidence indicates that thrombolysis may be an effective therapy for the treatment of acute ischemic stroke. However, the reperfusion of ischemic brain comes with a price. In clinical trials, patients treated with thrombolytic therapy have shown a 6% rate of intracerebral hemorrhage, which was balanced against a 30% improvement in functional outcome over controls. Destruction of the microvasculature and extension of the infarct area occur after cerebral reperfusion. We have reviewed the existing data indicating that an inflammatory response occurring after the reestablishment of circulation has a causative role in this reperfusion injury. The recruitment of neutrophils to the area of ischemia, the first step to inflammation, involves the coordinated appearance of multiple proteins. Intercellular adhesion molecule-1 and integrins are adhesion molecules that are up-regulated in endothelial cells and leukocytes. Tumor necrosis factor-alpha, interleukin-1, and platelet-activating factor also participate in leukocyte accumulation and subsequent activation. Therapies that interfere with the functions of these factors have shown promise in reducing reperfusion injury and infarct extension in the experimental setting. They may prove to be useful adjuncts to thrombolytic therapy in the treatment of acute ischemic stroke.

Brain biopsy using high-field strength interventional magnetic resonance imaging

OBJECTIVE Lesions within the brain are commonly sampled using stereotactic techniques. The advent of interventional magnetic resonance imaging (MRI) now allows neurosurgeons to interactively investigate specific regions, with exquisite observational detail. We evaluated the safety and efficacy of this new surgical approach. METHODS Between January 1997 and June 1998, 35 brain biopsies were performed in a high-field strength interventional MRI unit. All biopsies were performed using MRI-compatible instrumentation. Interactive scanning was used to confirm accurate positioning of the biopsy needle within the region of interest. Intraoperative pathological examination of the biopsy specimens was performed to verify the presence of diagnostic tissue, and intra- and postoperative imaging was performed to exclude the presence of intraoperative hemorrhage. Recently, magnetic resonance spectroscopic targeting was used for six patients. RESULTS Diagnostic tissue was obtained in all 35 brain biopsies and was used in therapeutic decision-making. Histological diagnoses included 28 primary brain tumors (12 glioblastomas multiforme, 9 oligodendrogliomas, 2 anaplastic astrocytomas, 2 astrocytomas, 1 lymphoma, and 1 anaplastic oligodendroglioma), 1 melanoma brain metastasis, 1 cavernous sinus meningioma, 1 cerebral infarction, 1 demyelinating process, and 3 cases of radiation necrosis. In all cases, magnetic resonance spectroscopy was accurate in distinguishing recurrent tumors (five cases) from radiation necrosis (one case). No patient sustained clinically or radiologically significant hemorrhage, as determined by intraoperative imaging performed immediately after the biopsy. One patient (3%) suffered transient hemiparesis after a pontine biopsy for investigation of a brain stem glioma. Another patient developed scalp cellulitis, with possible intracranial extension, 3 weeks after the biopsy; this condition was effectively treated with antibiotic therapy. Three patients were discharged on the day of the biopsy. CONCLUSION Interventional 1.5-T MRI is a safe and effective method for evaluating lesions of the brain. Magnetic resonance spectroscopic targeting is likely to augment the diagnostic yield of brain biopsies.

Outcomes after aneurysm rupture during endovascular coil embolization

OBJECTIVEIntracranial aneurysm rupture during placement of Guglielmi detachable coils has been reported, but the management and consequences of this event have not been extensively described. We present our experience with this feared complication and report possible neuroradiological and neurosurgical interventions to improve outcomes. METHODSWe retrospectively reviewed the records for 701 patients with 734 intracranial aneurysms that were treated with endovascular coiling, during a 6-year period, in the metropolitan Minneapolis-St. Paul (Minnesota) area. This analysis revealed 10 cases of perforation during coiling. The management and outcomes were recorded, and the pertinent literature was reviewed. RESULTSAll 10 cases involved previously ruptured aneurysms. This complication occurred sporadically and was not observed in the first 100 cases. Perforation occurred during microcatheterization of the aneurysm in two cases and during coil deposition in eight cases. Seven of the perforated aneurysms were located in the anterior circulation and three in the posterior circulation. Six of the 10 patients made good or fair recoveries; all three patients with posterior circulation lesions died immediately after rehemorrhage. Elevated intracranial pressure (ICP) was noted for all five patients with intraventricular catheters in place. Bilateral pupil dilation and profound hemodynamic changes were noted for eight patients. Coiling was rapidly completed, and total or nearly total occlusion was achieved in all cases. Emergency ventriculostomy was performed to rapidly reduce increased ICP for two patients, both of whom made good recoveries. Hemodynamic and angiographic factors after perforation, such as prolonged systemic hypertension, persistent dye extravasation after deployment of the first Guglielmi detachable coil, and persistent prolongation of contrast dye transit time (suggesting ongoing ICP elevation), were correlated with poor outcomes. CONCLUSIONPreviously ruptured aneurysms seem to be more susceptible to endovascular treatment-related perforation than are unruptured lesions. Worse prognoses are associated with iatrogenic rupture during coiling of posterior circulation lesions, compared with those in the anterior circulation. When perforation is recognized, the definitive treatment seems to be reversal of anticoagulation therapy and completion of Guglielmi detachable coil embolization. Immediate neurosurgical intervention is limited in these cases and focuses on decreasing ICP via emergency ventriculostomy. However, these measures may be life-saving, and neurosurgical assistance must be readily available during treatment of these cases.

High-field strength interventional magnetic resonance imaging for pediatric neurosurgery.

Background: Interventional magnetic resonance (MR) imaging allows neurosurgeons to interactively perform surgery using MR guidance. High-field (1.5-Tesla) strength imaging provides exceptional visualization of intracranial and spinal pathology. The full capabilities of this technology for pediatric neurosurgery have not been defined or determined. Materials and Methods: From January 1997 through June 1998, 10 of 85 cases performed in the interventional MR unit were in the pediatric population (mean age 8.3, median 8, range 2–15 years). Procedures included 2 brain biopsies, 5 craniotomies for tumor, 2 thoracic laminectomies for syringomyelia, and placement of a reservoir into a cystic brainstem tumor. The biopsies and reservoir placement were performed using MR-compatible equipment. Craniotomies and spinal surgery were performed with conventional instrumentation outside the 5-Gauss magnetic footprint. Interactive and intraoperative imaging was performed to assess the goals of surgery. Results: Both brain biopsies were diagnostic for cerebral infarct and anaplastic astrocytoma and the reservoir was optimally placed within the tumor cyst. Of the 5 tumor resections, all were considered radiographically complete. One biopsy patient and 1 tumor resection patient experienced transient neurological deficits after surgery. The patient with the thoracic syrinx required reoperation when the syringosubarachnoid shunt migrated into the syrinx 3 months after initial placement. No patient sustained a postoperative hemorrhage. Tumor histologies found at craniotomy were craniopharyngioma, ganglioglioma, and 3 low-grade gliomas. No evidence of tumor progression has been seen in any of these patients at a mean follow-up of 5.3 (range 4–8) months. The goals of the procedure were achieved in all 10 cases. There were no untoward events experienced related to MR-compatible instrumentation or intraoperative patient monitoring, despite the present inability to monitor core body temperature. Conclusions: 1.5-Tesla interventional MR is a safe and effective technology for assisting neurosurgeons to achieve the goals of pediatric neurosurgery. Preliminary results suggest that surgical resection of histologically benign tumors is enhanced in the interventional MR unit. The incidence of surgically related morbidity is low.

Rhinocerebral mucormycosis: changing patterns of disease.

Eleven cases of rhinocerebral mucormycosis (RM) encountered over a 13-year period were reviewed. Predisposing factors included leukemia (36%), diabetes mellitus (27%), aplastic anemia (9%), myelodysplastic syndrome (9%), and treatment with immunosuppressive medications necessary to maintain solid organ or bone marrow graft viability (64%). Two patients had no predisposing factors. Clinical findings included headache (73%), fever (55%), black nasal eschar (45%), orbitofacial cellulitis (36%), cranial nerve palsy (36%), altered sensorium (36%), and hemiparesis (27%). Seven patients presented with destruction of the paranasal sinuses and local invasion; three with direct extension to the frontal or temporal lobes. Four patients displayed hematogenous dissemination to the cerebrum, brain stem, and cerebellum from a primary pulmonary focus. The seven patients with sinus involvement were treated with aggressive surgical debridement. Two patients with focal intracerebral lesions underwent either open craniotomy or stereotactic biopsy. Amphotericin B was administered intravenously to all patients. Local irrigation via a percutaneous catheter was performed in the seven patients with sinus disease and in one case of intracranial abscess. All seven patients with intracranial infection died, in contrast to four patients that survived with infection localized to the sinuses and orbits. All survivors had been treated with a combination of surgery and amphotericin B therapy. This review demonstrates that RM is increasingly affecting patients with sources of immunosuppression other than diabetes mellitus. Early aggressive therapy to prevent cerebral involvement by this severe infection provides the best chance for a good outcome.

The pathogenesis of arteriovenous malformations: insights provided by a case of multiple arteriovenous malformations developing in relation to a developmental venous anomaly.

OBJECTIVE AND IMPORTANCE Developmental venous anomalies (DVAs) are common anomalies of intracranial venous drainage that may occur in conjunction with other cerebral vascular malformations. The present case raises important questions regarding the association between anomalous venous drainage patterns and the development of arteriovenous malformations (AVMs). CLINICAL PRESENTATION We present the case of a 24-year-old man with small AVMs fed by the superior cerebellar artery that drained directly into a large DVA of the cerebellum. INTERVENTION The patient was managed conservatively and returned 10 years later with recurrent symptoms. A repeat angiogram demonstrated spontaneous thrombosis of the previously documented AVMs; however, new AVMs at a different site that was also fed by the superior cerebellar artery and drained into the same DVA had appeared. The AVMs were completely embolized, and the DVA was left intact. CONCLUSION Recently, increasing attention has focused on the possible importance of venous outflow disturbance and venous hypertension in the pathogenesis and pathophysiology of AVMs. The potential mechanisms for this association and the implications of the present case are discussed, and the pertinent literature is reviewed.

Multiple Intracranial Aneurysms as Delayed Complications of an Atrial Myxoma: Case Report

OBJECTIVE AND IMPORTANCE Atrial myxomas are rare cardiac tumors that may cause neurological complications; however, delayed neurological events after total tumor resection are rare. In this report, we present a patient who developed transient cerebral ischemic attacks and was found to have multiple intracranial aneurysms 5 years after successful resection of her atrial myxoma. At the time of myxoma resection, there were no neurological symptoms; at the time of presentation with transient ischemic attacks, there was no evidence of atrial recurrence. CLINICAL PRESENTATION A 32-year-old woman presented with five episodes of right arm and face paresthesia, each lasting 15 to 20 minutes, 5 years after successful resection of her atrial myxoma. Clopidogrel bisulfate therapy was initiated, with resolution of her symptoms. Angiography revealed multiple, peripherally located, fusiform cerebral aneurysms. INTERVENTIONA left frontal craniotomy for resection and biopsy of one of the aneurysms was performed, to establish the diagnosis. Pathological analysis of the biopsied aneurysm provided evidence of direct atrial myxoma invasion and occlusion of the cerebral blood vessel. CONCLUSIONNeurological symptoms may accompany or lead to the diagnosis of atrial myxoma. Rarely, as in this case, myxomatous aneurysms may develop years after definitive treatment of the primary tumor. Patients who have undergone successful resection of a left atrial myxoma may be at risk for delayed cerebral ischemia associated with aneurysm development, and this phenomenon must be considered for patients with neurological symptoms who present even years after myxoma removal. The natural history, pathophysiological features, and treatment dilemma of these aneurysms are discussed.

Intra-aortic Balloon Counterpulsation Augments Cerebral Blood Flow in the Patient with Cerebral Vasospasm: A Xenon-enhanced Computed Tomography Study

OBJECTIVE We previously established the ability of intra-aortic balloon counterpulsation (IABC) to improve cerebral blood flow (CBF) significantly in a canine model of cerebral vasospasm. This study was performed to assess the efficacy of IABC in a patient with cardiac dysfunction and severe cerebral vasospasm that was refractory to traditional treatment measures. METHODS We report our experience with the clinical use of IABC to treat cerebral vasospasm in a patient who suffered subarachnoid hemorrhage and concomitant myocardial infarction. Hypertensive, hypervolemic, hemodilution therapy was ineffective, and IABC was instituted. Xenon-enhanced computed tomography (Xe-CT) was utilized to obtain serial measurements of CBF with and without IABC over a 4-day period. RESULTS IABC dramatically improved cardiac function in this patient, and Xe-CT demonstrated significant improvement in CBF with IABC. The average global CBF was 20.5 +/- 4.4 ml/100g/min before versus 34.7 +/- 3.8 ml/100g/min after IABC (p < 0.0001, paired students t-test). The lower the CBF before IABC, the greater the improvement with IABC (correlation coefficient r = 0.83, p = 0.0007). CBF improvement ranged from 33% to 161% above baseline, average 69.3%. No complications of IABC were observed. CONCLUSIONS This is the first report demonstrating the ability of IABC to improve CBF in a patient with vasospasm. We suggest that IABC is a rational treatment option in select patients with refractory cerebral vasospasm who do not respond to traditional treatment measures.

Complete temporal lobectomy for surgical resuscitation of patients with transtentorial herniation secondary to unilateral hemisphearic swelling.

Transtentorial herniation is an ominous finding in the patient with head injuries. We report our experience with 10 patients suffering from acute transtentorial herniation secondary to posttraumatic unilateral hemispheric swelling who were treated aggressively with temporal lobectomy. Eight patients were men and 2 were women. Their ages ranged from 22 to 61 years, with a mean of 37 years. Their preoperative Glasgow Coma Scale scores ranged from 3 to 6, with a mean of 4. All patients had both computed tomographic and clinical evidence of unilateral hemispheric shift and acute herniation without a significant subdural or epidural hematoma. Seven patients had unilateral nonreactive pupils and 3 had bilateral nonreactive pupils. All were taken to the operating room within 2 hours of clinical signs of herniation. Complete unilateral temporal lobectomies including the mesial structures, amygdala, and uncus were performed. In this series, the mortality rate was 30%, including a single patient who was neurologically stable but died from nonneurological injuries. Of the 7 survivors, 4 were functionally independent and 3 required minimal assistance with the activities of daily living. Aggressive, early decompression via complete temporal lobectomy may thus significantly improve the outcome in patients with transtentorial herniation accompanying posttraumatic hemispheric swelling and midline shift.

Dissecting aneurysms of the posterior inferior cerebellar artery: retrospective evaluation of management and extended follow-up review in 6 patients.

OBJECT The authors report the management protocol and successful outcomes in 6 patients with dissecting aneurysms of the posterior inferior cerebellar artery (PICA). METHODS Medical records and neuroimaging studies of 6 patients who underwent surgical treatment of dissecting PICA aneurysms were reviewed. The mean follow-up duration was 1.8 years. No patient was lost to follow-up review. RESULTS Four patients presented with acute subarachnoid hemorrhage and 2 with PICA ischemia. All patients underwent surgery, which entailed proximal occlusion with distal revascularization in 3 cases and circumferential wrap/clip reconstruction in 3 cases. The revascularization techniques used were occipital artery-PICA bypass and PICA-PICA anastomosis. Delayed follow-up angiography was performed in all cases. In patients treated with proximal occlusion, delayed angiography showed minimal retrograde opacification of the dissected segments. The 3 patients treated with wrap/clip reconstruction showed unexpectedly significant normalization of their lesions on angiographic studies. Outcome was good in all cases. CONCLUSIONS Dissecting PICA aneurysms are rare lesions with an apparent propensity for bleeding. Individualized management including distal revascularization with PICA sacrifice or circumferential wrap/clip reconstruction to reinforce the dissected segment produced good outcomes. Patients treated with aneurysm wrapping may show dramatic angiographic improvement of the dissected segment.