Posttraumatic Uncal Herniation in a Conscious Patient.

The incidence of primary traumatic oculomotor nerve palsies in craniocerebral trauma is approximately 1.2% and is usually persistent and associated with loss of consciousness, other neurologic deficits, and skull base or orbital fractures. This case is a rare demonstration of complete left third nerve palsy from uncal herniation after trauma without any loss of consciousness.

Intraventricular Glioblastomas.

BACKGROUND AND IMPORTANCE: Although glioblastoma is the most common primary brain tumor, primary intraventricular locations are extremely rare; only 21 cases have been reported to date. METHODS: A retrospectively acquired database of all intracranial glioblastomas treated in 2 different neurosurgical departments during the last 10 years was queried. Patients with histologically proven intraventricular glioblastomas were included in the study. RESULTS: Eight patients were identified as having a histologically confirmed intraventricular glioblastoma. Patient age at diagnosis ranged from 6 to 74 years (mean 29.6 years) and the male/female ratio was 5:3. Increased intracranial pressure due to hydrocephalus was the main cause of the clinical manifestations. The tumor was located within the lateral ventricle in 6 cases and the anterior third ventricle in 2 others. Gross total tumor excision was achieved in 3 patients, whereas the surgical resection was subtotal in 4 cases and a surgical biopsy was performed in 1 patient. Postoperative adjuvant therapies were administered in 5 patients. Median survival time was 32.1 months, and 3 patients were alive at the end of study. All of them had isocitrate dehydrogenase-mutated tumors. CONCLUSIONS: Intraventricular glioblastoma is extremely rare and can affect younger individuals including children. This malignant tumor should be included in the differential diagnosis of intraventricular lesions, especially in the lateral ventricles. Radical surgical resection can be associated with remarkable disease-free survival, especially in isocitrate dehydrogenase-mutated tumors. Because recurrence virtually is unavoidable, long-term follow-up is mandatory.

Primary Cerebellar Gliosarcoma with Extracranial Metastases: An Orphan Differential Diagnosis.

BACKGROUND: Gliosarcomas are rare, malignant primary brain tumors, most commonly located in the temporal lobe, that contain both glial and mesenchymal elements. Gliosarcomas located within the cerebellum are exceedingly rare. The previously unreported finding of a cerebellar gliosarcoma concurrently with an extracranial metastasis to the lungs is discussed here. CASE DESCRIPTION: A 57-year-old man presented with a 3-month history of chest pain, weight loss, headaches, and vomiting. Physical examination revealed a left cerebellar dysfunction, and the radiological work-up revealed a 6 × 6-cm right apical pulmonary tumor and a 4 × 3.5 × 3.8-cm peripherally enhancing left cerebellar mass. On the basis of a smoking history in the setting of a lung lesion and cerebellar mass, the presumptive diagnosis was primary lung cancer with metastasis to the cerebellum. Gross total resection of a firm pseudo-encapsulated cerebellar mass was performed. The microscopic features and the immunohistochemical profile confirmed the diagnosis of Gliosarcoma. The thoracic lesion was removed subsequently, and pathology confirmed it as an extracranial metastasis from the cerebellar gliosarcoma. Adjuvant radiation and chemotherapy were then administered. No clinical or radiographic evidence of recurrence was observed during one year of follow-up monitoring. CONCLUSIONS: To the best of our knowledge, a primary infratentorial gliosarcoma with extracranial metastases has not been previously described.

Calcified Suprasellar Xanthogranuloma Presenting with Primary Amenorrhea in a 17-Year-Old Girl: Case Report and Literature Review.

BACKGROUND: Xanthogranuloma, also known as cholesterol granuloma, is an extremely rare intracranial neoplasm most commonly located in the middle ear, petrous apex, or choroid plexus. Exclusively suprasellar xanthogranulomas are exceptional and this report presents a very rare case in the pediatric population, particularly unique due to the presence of calcification. CASE DESCRIPTION: A 17-year-old girl presented with primary amenorrhea with computed tomography and magnetic resonance imaging showing a large calcified enhancing suprasellar mass, which was presumptively diagnosed as a craniopharyngioma on the basis of its clinical and radiologic appearance. Gross total resection of a well-encapsulated, exclusively suprasellar tumor was achieved, without postoperative neurologic deficits. Histologic examination found fibrous tissue with abundant cholesterol clefts, multinucleated giant cells, and hemosiderin deposits but no epithelial cells. The final histologic diagnosis was a xanthogranuloma. CONCLUSIONS: Xanthogranuloma, although extremely rare in the pediatric population, may present as a calcified suprasellar mass and manifest with primary amenorrhea. The prognosis after gross total resection is likely favorable; however, long-term follow-up is indicated for these rare neoplasms.

Simple technique for intraoperative angiographic localization of small vascular lesions.

BACKGROUND: Precise surgical localization of small arteriovenous malformations (AVMs), arteriovenous fistulae (AVFs), and aneurysms located in the distal portions of the intracranial arteries can be difficult. OBJECTIVE: We describe a simple and accurate intraoperative angiographic localization technique for small AVMs, AVFs, and distal aneurysms. METHODS: All patients had routine preoperative diagnostic imaging and evaluations, including catheter angiography. Once anesthetized, the patients were prepared for intraoperative angiography following cannulation of the femoral artery. Craniometric landmarks were utilized to approximately localize the lesion. A wire in the shape of a square was placed over the proposed craniotomy site and an angiogram was performed. With use of real-time angiography, the wire localizer was manipulated until the small vascular lesion was visualized entirely within the wire frame, thus defining the extent of the required craniotomy and the surgical trajectory. RESULTS: The wire localizer was used to target small vascular lesions in 9 cases of AVMs, 4 cases of distal middle cerebral artery aneurysms, and 1 case of a diploic AVF. In all 14 cases, the lesion was accurately localized intraoperatively without further image-guided techniques, and there was no change in the craniotomy. There were no intraoperative complications, and all patients had uneventful recoveries. CONCLUSION: Intraoperative angiography with a simple wire localizer can effectively and accurately aid in the planning of surgery for a range of small and distal vascular lesions with virtually no added cost, minimal setup time, and limited potential for technical errors.

Frontozygomatic titanium cranioplasty in frontosphenotemporal ("pterional") craniotomy.

OBJECTIVE: One of the most common problems after frontosphenotemporal, or pterional, craniotomy is the marked depression of the frontozygomatic fossa caused by atrophy of the temporalis muscle. Although temporalis muscle reconstruction techniques have been proposed to prevent this problem, a definitive solution has not been achieved. We report the results of a titanium cranioplasty technique in a prospective series of patients who underwent frontosphenotemporal craniotomy. METHODS: Between April 2002 and June 2006, 209 consecutive patients underwent a frontosphenotemporal craniotomy for aneurysms, vascular malformations, or tumors. At the time of surgery, the patients underwent a frontozygomatic fossa cranioplasty with a titanium plate, to which the temporalis muscle was attached. In this series, 194 patients had documented follow-up periods averaging 9.5 months (range, 1 mo-4 yr; median, 7.5 mo), and the cosmetic results of the cranioplasty have been assessed. RESULTS: The cosmetic outcomes have been outstanding in all patients treated to date. Two patients had the cranioplasty removed due to either orbital pain or local infection secondary to sepsis. CONCLUSION: The frontozygomatic cranioplasty during frontosphenotemporal craniotomy prevents the characteristic depression at the frontozygomatic fossa and accomplishes an outstanding cosmetic result.

Repeat stereotactic radiosurgery for high-grade and large intracranial arteriovenous malformations.

BACKGROUND: The treatment of large and high-grade (Spetzler-Martin III-V) AVMs remains a challenge. There is a paucity of literature addressing the efficacy of radiosurgery in this group. We retrospectively analyze our experience with repeat radiosurgery with such AVMs. METHODS: Between 1989 and 2004, 14 patients with large and high-grade AVMs deemed to be nonoperative candidates were treated with repeat radiosurgery. Patients were treated either on a LINAC or gamma knife-based system at 2- to 3-year intervals with targeting of the entire nidus with each treatment. Patients who did not receive their full treatment course or follow-up at the institution were excluded. RESULTS: Mean follow-up was 18 months. The complete obliteration rate was 35.7%, with a mean volume reduction of 53% in the remaining lesions. Twenty percent of grade III and 50% of grade IV lesions experienced cure. Complications included persistent headaches (2 patients). Statistical analysis revealed no difference between obliterated and partially obliterated groups with regard to mean pretreatment volume (24.87 cm(3)), median Spetzler-Martin grade (IV), mean follow-up (30.5 months), total delivered dose (3550 cGy), mean dose per stage (13 Gy), median number of stages (2), or mean interval between treatment stages (40 months). CONCLUSION: The present study demonstrates the potential role of repeat radiosurgery in the treatment of this cohort in the context of our short follow-up. The benefits of repeat therapy could be derived from using lower doses per session and repeat targeting of the lesion in an effort to increase response and decrease complication rates.

Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood.

OBJECTIVE: Leukocyte-endothelial cell interactions appear to play a role in the development of vasospasm after SAH. Using a purely inflammatory protein, LPS, we evaluated the effect of inflammation on the development of chronic vasospasm in the absence of blood and compared it to SAH-induced vasospasm in rabbits. METHODS: Lipopolysaccharide was incorporated into EVAc polymers to produce 20% LPS/EVAc polymers (wt/wt). Rabbits (n = 23) were randomized to 4 experimental groups: (1) empty polymer (n = 6), (2) SAH (n = 5), (3) 0.7 mg/kg polymeric LPS dose (n = 6), and (4) 1.4 mg/kg polymeric LPS dose (n = 6). Blood and polymers were inserted into the cisterna magna. The rabbits were killed 3 days postoperatively, and the basilar arteries were harvested for morphometric analysis. Clinical response and lumen patencies were analyzed using ANOVA and a post hoc Newman-Keuls Multiple Comparisons test. RESULTS: Significant narrowing of the basilar artery was observed by insertion of 20% LPS/EVAc polymers into the subarachnoid space at a polymeric dose of 1.4 mg/kg (actual dose, 66 microg kg(-1) d(-1)) (75.4% +/- 4.2%; P < .01) and by SAH (80.3% +/- 8.1%; P < .01) as compared with the empty polymer group. A trend toward narrowing was observed in the 0.7 mg/kg polymeric LPS dose group (actual dose, 33 microg kg(-1) d(-1)) (85.2% +/- 2.6%; P > .05). Symptoms associated with SAH were noted in 50% of the rabbits in the 0.7 mg/kg LPS group and in 100% of rabbits in the 1.4 mg/kg LPS group. CONCLUSION: Controlled release of LPS into the subarachnoid space of rabbits produced chronic vasospasm in a dose-dependent manner. At a polymeric dose of 1.4 mg/kg, LPS-induced vasospasm was equivalent to that induced by SAH. This suggests that LPS and SAH may induce vasospasm through similar mechanisms and provides further evidence that inflammation plays a central role in the etiology of chronic vasospasm.

Lysis of intracerebral hematoma with stereotactically implanted tissue plasminogen activator polymers in a rabbit model.

OBJECT: Currently no adequate surgical treatment exists for spontaneous intracerebral hemorrhage (ICH). Implantable polymers can be used effectively to deliver therapeutic agents to the local site of the pathological process, thus reducing adverse systemic effects. The authors report the use of stereotactically implanted polymers loaded with tissue plasminogen activator (tPA) to induce lysis of ICH in a rabbit model. METHODS: Ethylene vinyl acetate (EVAc) polymers were loaded with bovine serum albumin (BSA) only or with BSA plus tPA. In vitro pharmacokinetic (three polymers) and thrombolysis (12 polymers) studies were performed. For the in vivo study, 12 rabbits were fixed in a stereotactic frame, and 0.2 ml of clotted autologous blood was injected into the right frontal lobe parenchyma. After 20 minutes, control BSA polymers were stereotactically implanted at the hemorrhage site in six rabbits, and experimental BSA plus tPA polymers were implanted in six rabbits. Animals were killed at 3 days, and blood clot volume was assessed. The pharmacokinetic study showed release of 146 ng of tPA over 3 days. The tPA activity correlated with in vitro thrombolysis. In the in vivo study, the six animals treated with tPA polymers had a mean (+/- standard error of the mean [SEM]) thrombus volume of 1.43 +/- 0.29 mm3 at 3 days, whereas the six animals treated with blank (BSA-only) polymers had a mean (+/- SEM) thrombus volume of 19.99 +/- 3.74 mm3 (p < 0.001). CONCLUSIONS: Ethylene vinyl acetate polymers release tPA over the course of 3 days. Stereotactic implantation of tPA-loaded EVAc polymers significantly reduced ICH volume. Polymers loaded with tPA may be useful clinically for lysis of ICH without the side effects of systemic administration of tPA.

Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers.

Lactacystin, a proteasome-inhibitor, has been shown to induce apoptosis of experimental gliomas in vitro. However, its systemic toxicity prevents further clinical use. To circumvent this problem, lactacystin can be delivered intratumorally. We tested the efficacy of lactacystin incorporated into controlled-release polymers for treating experimental gliomas. 9L-gliosarcoma and F98-glioma cell lines were treated with lactacystin (10-100 microg/ml) for 72 h in vitro. Cell-viability was measured with MTT-assays. Toxicity of lactacystin/polycarboxyphenoxypropane-sebacic-acid (pCPP : SA) polymers was tested in vivo using Fischer-344 rats intracranially implanted with lactacystin polymers loaded from 0.1 to 2% lactacystin by weight. The efficacy of 1, 1.3, 1.5 and 1.7% lactacystin/pCPP : SA polymers was determined in Fischer-344 rats intracranially challenged with 9L and treated either simultaneously or 5 days after tumor implantation. Lactacystin was cytotoxic in 9L cells, causing a 16 +/- 8% growth inhibition at 10-microg/ml that increased to 78 +/- 4% at 100-microg/ml. Similarly, lactacystin inhibited growth of F98 by 18 +/- 8% at 10-microg/ml and 74 +/- 2% at 100-microg/ml in vitro. Polymers released lactacystin for 21 days and intracranial implantation in rats neither generate local nor systemic toxicity at doses lower than 2%. Treatment with lactacystin/pCPP : SA polymers with loading concentrations of 1.0, 1.3, and 1.5% prolonged survival of animals intracranially challenged with 9L when polymers where inserted in the day of tumor implantation. In conclusion, lactacystin exhibits potent cytotoxic-activity against 9L and F98 in vitro, it can be efficiently incorporated and delivered using controlled-release polymers, and at the proposed concentrations lactacystin polymers are safe for CNS delivery and prolong survival in the 9L model.

Systemic administration of simvastatin after the onset of experimental subarachnoid hemorrhage attenuates cerebral vasospasm.

OBJECTIVE: Experimental evidence suggests that intercellular adhesion molecule-1 mediated leukocyte extravasation contributes to the pathogenesis of cerebral vasospasm. Simvastatin, an HMG-CoA reductase inhibitor, decreases intercellular adhesion molecule-1 expression and competitively inhibits leukocyte intercellular adhesion molecule-1 binding. We hypothesized that administration of simvastatin after the onset of subarachnoid hemorrhage (SAH) would attenuate perivascular granulocyte migration and ameliorate cerebral vasospasm in a rabbit model of SAH. METHODS: New Zealand white rabbits (n = 15) underwent injection of autologous blood into the cisterna magna or sham surgery followed by subcutaneous injection of simvastatin (40 mg/kg) or vehicle 30 minutes, 24 hours, and 48 hours after SAH or sham surgery. Seventy-two hours later, basilar artery lumen diameter was measured by in situ perfusion/fixation and image analysis. CD-18 monoclonal antibody stained perivascular granulocytes and macrophages were counted under light microscopy. RESULTS: In vehicle treated rabbits, mean +/- standard deviation basilar artery diameter was reduced 3 days after SAH (n = 5) versus sham (n = 5) rabbits (0.49 +/- 0.08 mm versus 0.75 +/- 0.03 mm, P < 0.01). After SAH, mean +/- standard deviation basilar artery diameter was greater in simvastatin (n = 5) treated rabbits versus vehicle (n = 5) (0.63 +/- 0.04 mm versus 0.49 +/- 0.08 mm, P < 0.01). In vehicle treated rabbits, SAH resulted in an increase in the mean +/- standard deviation perivascular CD18 cell count (sham-vehicle, 2.8 +/- 2; SAH-vehicle 90 +/- 27; P < 0.01). Subcutaneous administration of simvastatin attenuated this increase in perivascular CD18-positive cells after SAH (SAH statin, 41.6 +/- 13; SAH vehicle, 90 +/- 27; P < 0.001). CONCLUSION: Subcutaneous administration of simvastatin after the onset of SAH attenuates perivascular granulocyte migration and ameliorates basilar artery vasospasm after experimental SAH in rabbits. 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, such as simvastatin, may potentially serve as agents in the prevention of cerebral vasospasm after SAH.

Aneurysmal rupture without subarachnoid hemorrhage: case series and literature review.

OBJECTIVE: Although an aneurysmal rupture typically presents on computed tomographic (CT) imaging as only subarachnoid hemorrhage (SAH), it may be associated with intraparenchymal hemorrhage (IPH), intraventricular hemorrhage (IVH), or subdural hemorrhage. On rare occasions, however, an aneurysmal rupture may present with IPH or IVH without SAH. METHODS: The Division of Cerebrovascular Neurosurgery at The Johns Hopkins Medical Institutions maintains a prospective database of all patients treated for intracranial aneurysms at this institution since 1991. Using this database, we identified patients with ruptured aneurysms who presented with IPH or IVH in the absence of SAH on CT imaging. RESULTS: Eight hundred twenty-two patients with radiographically documented ruptured aneurysms were admitted from January 1991 through June 2004. Of these, nine patients presented with IPH only, three with IPH and IVH, and one with IVH only, for a total of 13 cases. There were seven posterior communicating artery, four middle cerebral artery, one basilar apex, and one posterior cerebral artery aneurysms. The incidence of aneurysmal rupture with IPH and/or IVH without SAH is 1.6% CONCLUSION: Initial presentation of a ruptured aneurysm without SAH is rare and may have a multifactorial cause attributable to the timing of CT imaging, physiological parameters, or location of the aneurysm. Patients presenting with a head CT scan revealing IPH in the temporal lobe or with IVH should be considered for an urgent workup of a ruptured aneurysm, even in the absence of diffuse SAH.

Local delivery of ibuprofen via controlled-release polymers prevents angiographic vasospasm in a monkey model of subarachnoid hemorrhage.

OBJECTIVE: Adhesion and migration of leukocytes into the periadventitial space play a role in the pathophysiology of vasospasm after subarachnoid hemorrhage (SAH). Intercellular adhesion molecule-1 is a determinant cell adhesion molecule involved in this process. Ibuprofen has been shown to inhibit intercellular adhesion molecule-1 upregulation and prevent vasospasm in animal models of SAH. In this study, we report the toxicity and efficacy of locally delivered ibuprofen incorporated into controlled-release polymers to prevent vasospasm in a monkey model of SAH. METHODS: Ibuprofen was incorporated into ethylene-vinyl acetate (EVAc) polymers at 45% loading (wt:wt). For the toxicity study, cynomolgus monkeys (n = 5) underwent surgical implantation of either blank/EVAc polymers (n = 3) or 45% ibuprofen/EVAc polymers (n = 2) in the subarachnoid space, were followed up for 13 weeks, and were killed for histopathological analysis. For the efficacy study, cynomolgus monkeys (n = 14) underwent cerebral angiography 7 days before and 7 days after surgery and SAH and were randomized to receive either a 45% ibuprofen/EVAc polymer (n = 7; mean dose of ibuprofen, 6 mg/kg) or blank EVAc polymers (n = 7) in the subarachnoid space. Angiographic vasospasm was determined by digital image analysis. Student's t test was used for analysis. RESULTS: Animals implanted with ibuprofen polymers showed no signs of local or systemic toxicity. Animals treated with ibuprofen polymers had 91 +/- 9% lumen patency of the middle cerebral artery, compared with 53 +/- 11% of animals treated with blank/EVAc polymers (P < 0.001). CONCLUSION: Ibuprofen polymers are safe and prevent angiographic vasospasm after SAH in the monkey model. These findings support the role of cell adhesion molecules and inflammation in the pathophysiology of vasospasm.

Local delivery of antineoplastic agents by controlled-release polymers for the treatment of malignant brain tumours.

Recent advances in the treatment of malignant brain tumours have focused on the development of targeted local delivery of therapeutic agents, which combine various antineoplastic strategies that include cytotoxic, anti-angiogenic and immunomodulatory mechanisms, among others. The introduction of local delivery devices for sustained administration of antineoplastic agents represents a new opportunity to effectively treat these malignancies by facilitating the intracranial administration of safe and clinically efficacious doses for prolonged periods of time in a controlled fashion. This technology circumvents the need for high systemic doses with potentially harmful toxicities, bypasses the blood-brain barrier and can be tailored to deliver new agents with complex pharmacological properties. Based on local delivery strategies, new delivery systems, including convection-enhanced delivery and microchips, have been developed. As a result, recent advances in tumour biology have been adopted as potentially translatable treatments and are undergoing preclinical and clinical evaluation at present. These novel approaches could improve the prognosis of patients with these tumours.

Delayed intracranial delivery of a nitric oxide donor from a controlled-release polymer prevents experimental cerebral vasospasm in rabbits.

OBJECTIVE: Decreased local availability of nitric oxide (NO) may mediate chronic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Previous reports have shown that early treatment with NO prevents vasospasm in animals. We evaluated the efficacy of controlled-release polymers that contain the NO donor diethylenetriamine (DETA-NO) for the delayed treatment of vasospasm in a rabbit model of SAH. METHODS: DETA-NO 20% (wt/wt) was incorporated into ethylene-vinyl acetate (EVAc) polymers. Animals (n = 52) were randomized to two experimental groups. In the first group (n = 32), animals received SAH and implantation of either 20% DETA-NO/EVAc polymer at a dose of 0.5 mg/kg of DETA-NO (n = 16) or empty EVAc polymer (n = 16). Polymers were implanted 24 (n = 16) or 48 hours (n = 16) after SAH. In the second group (n = 20), animals received SAH and implantation of either 20% DETA-NO/EVAc polymer at a dose of 1.3 mg/kg (n = 10) or empty EVAc (n = 10). Polymers were implanted 24 (n = 10) or 48 hours (n = 10) after SAH. An additional group (n = 16) underwent either sham operation (n = 6) or SAH only (n = 10). Animals were killed 3 days after hemorrhage, and the basilar arteries were processed for morphometric measurements. Results were analyzed using Student's t test. RESULTS: Treatment with 20% DETA-NO/EVAc polymers at a dose of 1.3 mg/kg significantly increased basilar artery lumen patency when administered at 24 (97 +/- 6% versus 73 +/- 10%; P = 0.0396) or 48 hours (94 +/- 6% versus 71 +/- 9%; P = 0.03) after SAH. Treatment with 20% DETA-NO/EVAc polymers at a dose of 0.5 mg/kg administered 48 hours after SAH significantly increased lumen patency (82 +/- 8% versus 68 +/- 12%; P = 0.03); a dose of 0.5 mg/kg, 24 hours after SAH, did not reach statistical significance (74 +/- 7% versus 65 +/- 9%; P = 0.16). The SAH-only group had a lumen patency of 67 +/- 12%. CONCLUSION: Delayed treatment of SAH with controlled-release DETA-NO polymers prevented experimental posthemorrhagic vasospasm in the rabbit. This inhibition was dose-dependent. This further confirms the role of NO in the pathogenesis of vasospasm.