Louis J. Kim

Dehydroascorbic acid, a blood–brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke

Neuronal injury in ischemic stroke is partly mediated by cytotoxic reactive oxygen species. Although the antioxidant ascorbic acid (AA) or vitamin C does not penetrate the blood–brain barrier (BBB), its oxidized form, dehydroascorbic acid (DHA), enters the brain by means of facilitative transport. We hypothesized that i.v. DHA would improve outcome after stroke because of its ability to cross the BBB and augment brain antioxidant levels. Reversible or permanent focal cerebral ischemia was created by intraluminal middle cerebral artery occlusion in mice treated with vehicle, AA, or DHA (40, 250, or 500 mg/kg), either before or after ischemia. Given before ischemia, DHA caused dose-dependent increases in postreperfusion cerebral blood flow, with reductions in neurological deficit and mortality. In reperfused cerebral ischemia, mean infarct volume was reduced from 53% and 59% in vehicle- and AA-treated animals, respectively, to 15% in 250 mg/kg DHA-treated animals (P < 0.05). Similar significant reductions occurred in nonreperfused cerebral ischemia. Delayed postischemic DHA administration after 15 min or 3 h also mediated improved outcomes. DHA (250 mg/kg or 500 mg/kg) administered at 3 h postischemia reduced infarct volume by 6- to 9-fold, to only 5% with the highest DHA dose (P < 0.05). In contrast, AA had no effect on infarct volumes, mortality, or neurological deficits. No differences in the incidence of intracerebral hemorrhage occurred. Unlike exogenous AA, DHA confers in vivo, dose-dependent neuroprotection in reperfused and nonreperfused cerebral ischemia at clinically relevant times. As a naturally occurring interconvertible form of AA with BBB permeability, DHA represents a promising pharmacological therapy for stroke based on its effects in this model of cerebral ischemia.

Classification and Surgical Management of Spinal Arteriovenous Lesions: Arteriovenous Fistulae and Arteriovenous Malformations

OBJECTIVE:Preexisting spinal arteriovenous malformation nomenclature can be confusing. The aim of this article is to present a modified classification system for spinal arteriovenous lesions and to discuss its implications for microsurgical strategies. METHODS:Based on the literature review of prior classifications as well as on the experience of the senior author (RFS), the authors delineate an anatomically and pathophysiologically based classification to facilitate the description and treatment of these uncommon entities. RESULTS:Spinal arteriovenous lesions are composed of arteriovenous fistulae and malformations. These lesions are classified as extradural, extradural-intradural, or intradural. Intradural lesions are characterized further as ventral or dorsal fistulae or as intramedullary lesions. Intramedullary lesions are characterized as compact or diffuse. A new category, conus medullaris arteriovenous malformations, is described as a distinct entity. CONCLUSION:This updated classification system eliminates confusion related to older nomenclature and is based on the anatomical and pathophysiological features of these lesions. When treating these lesions, the neurovascular team must collaborate closely with their microsurgical and endovascular colleagues. Finally, treatment should be individualized, depending on lesional angioarchitecture and the patients clinical status.

Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke.

Background and Purpose Although the deleterious role of several proinflammatory mediators, including P-selectin, in reperfused stroke is well established, the role of E-selectin has not been fully characterized. Methods E-selectin mRNA expression was studied at 4, 10, and 24 hours after reperfusion with reverse transcription and polymerase chain reaction in mice (n=18) subjected to transient intraluminal middle cerebral artery occlusion (MCAO). Mice received intravenous injection with anti–E-selectin monoclonal antibody (10, 35, or 50 &mgr;g), nonimmune IgG, or vehicle immediately before MCAO and 90 minutes later (n=85). Others received anti–E-selectin antibody 3 or 6 hours after MCAO (n=32). Myeloperoxidase activity was measured in sham-operated mice and after 10 hours of reperfusion in saline-, nonimmune IgG–, or anti–E-selectin IgG–treated cohorts (n=17). Serial cerebral blood flow was measured with laser-Doppler flowmetry, and outcomes were assessed by neurological deficits and infarct volumes with the use of planimetric analysis of triphenyltetrazolium chloride–stained sections. Results Upregulated E-selectin expression occurred in the ischemic cerebral vasculature within 4 hours of reperfusion and persisted for 24 hours. Anti–E-selectin antibody increased ischemic cortical cerebral blood flow up to 2.6-fold (P <0.05). In addition to dose-dependent reductions in neurological deficits (P <0.05), mortality, and infarct volumes (P <0.01 for 35 and 50 &mgr;g), anti–E-selectin treatment reduced cerebral neutrophil accumulation (P <0.05) and was neuroprotective even if delayed until 3 hours after ischemia (P <0.05). Conclusions These findings establish a functional role for E-selectin in the pathogenesis of tissue injury after cerebral ischemia and reperfusion and suggest that E-selectin blockade may be clinically useful in the treatment of reperfused stroke.

Evolution of surgical approaches in the treatment of petroclival meningiomas: a retrospective review.

OBJECTIVE We examined the surgical approaches used at a single institution to treat petroclival meningioma and evaluated changes in method utilization over time. METHODS Craniotomies performed to treat petroclival meningioma between September of 1994 and July of 2005 were examined retrospectively. We reviewed 46 patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or transcochlear approaches (15% of patients), retrosigmoid craniotomies with or without some degree of petrosectomy (59% of patients), orbitozygomatic craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid approaches (19% of patients). In 18 patients, the tumor extended supratentorially. Overall, the rate of gross total resection was 43%. Seven patients demonstrated progression over a mean of 5.9 years. No patients died. At 36 months, the progression-free survival rate for patients treated without petrosal approaches was 96%. Of 14 patients treated with stereotactic radiosurgery, none developed progression. CONCLUSION Over the study period, a diminishing proportion of patients with petroclival meningioma were treated using petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid approaches alone or in combination provided a viable alternative to petrosal approaches for treatment of petroclival meningioma. Regardless of approach, progression-free survival rates were excellent over short-term follow-up period.

Safety and accuracy of bedside external ventricular drain placement.

OBJECTIVE To study the safety and accuracy of ventriculostomy by neurosurgical trainees. METHODS Initial computed tomographic studies of 346 consecutive patients who underwent bedside ventriculostomy were reviewed retrospectively. Diagnosis, catheter tip location, midline shift, and procedural complications were tabulated. To analyze catheter placement, we used a new grading system: Grade 1, optimal placement in the ipsilateral frontal horn or third ventricle; Grade 2, functional placement in the contralateral lateral ventricle or noneloquent cortex; and Grade 3, suboptimal placement in the eloquent cortex or nontarget cerebrospinal fluid space, with or without functional drainage. Statistical analysis was performed using Fishers exact test and a weighted κ coefficient. RESULTS Diagnoses included the following: subarachnoid hemorrhage, n = 153 (44%); trauma, n = 64 (18%); intracerebral hemorrhage/intraventricular hemorrhage, n = 63 (18%); and other, n = 66 (20%). There were 266 (77%) Grade 1, 34 (10%) Grade 2, and 46 (13%) Grade 3 catheter placements. Hemorrhagic complications occurred in 17 (5%). Four patients (1.2%) were symptomatic, with two (0.6%) requiring surgery. Inter- and intraobserver agreement was almost perfect (κ = 0.846 and 0.922, respectively) as applied to our grading system. Rates of suboptimal placement were highest in patients with midline shift (P = 0.059) and trauma (P = 0.0001). Rates of optimal placement were highest in patients with subarachnoid hemorrhage (P = 0.003) and when the catheter was placed ipsilateral to the side of midline shift (P = 0.063). Neither the residents training experience nor the side of placement seemed to affect accuracy. CONCLUSION Bedside ventriculostomy is a safe and accurate procedure for intracranial pressure monitoring and cerebrospinal fluid drainage.

Neurosurgical management of intracranial aneurysms previously treated with endovascular therapy.

OBJECTIVEWith the increased use of endovascular therapy, an increasing number of patients with incompletely treated intracranial aneurysms are presenting for further surgical management. This study reviews our experiences with such patients. METHODSDuring a 7-year period, 38 patients with 40 intracranial aneurysms who were initially treated with endovascular therapy underwent surgical obliteration of refractory or recurrent lesions. All patients were recorded in a prospective registry, and their clinical data and imaging studies were analyzed retrospectively. RESULTSTwenty-six anterior and 14 posterior circulation aneurysms were treated. Four aneurysms were on the cavernous internal carotid artery, 13 were on the distal internal carotid artery, 6 were on the anterior communicating artery complex, 2 were on the middle cerebral artery, 3 were on the posteroinferior cerebellar artery, 1 was at the vertebrobasilar junction, 3 were on the superior cerebellar artery, 4 were at the basilar apex, 2 were on the posterior cerebral artery, and 1 was on the distal vertebral artery. Two pseudoaneurysms—one on the petrocavernous segment of the internal carotid artery and one on the distal VA—also were treated. The median time until recurrence was 6 months. Thirty-one aneurysms were clip-ligated, and six were treated with trapping. Three extracranial-intracranial bypasses were performed. One aneurysm was treated with muslin wrapping. Two aneurysms required the use of surgical approaches that involved hypothermic circulatory arrest. Nine aneurysms required coil mass extraction and/or complex vascular reconstruction to complete lesion obliteration. All aneurysms except the single wrapped aneurysm were successfully excluded from the intracranial circulation. Two deaths occurred as a result of the operative procedures, and another patient died as a result of subarachnoid hemorrhage-induced massive myocardial infarction. Ultimately, 86.8% of patients achieved an excellent or good recovery. CONCLUSIONWith endovascular therapy assuming an increasing role in the treatment of patients with intracranial aneurysms, more lesions that are refractory to initial treatment will require surgical management. Our experience indicates that good results are attainable, although technical challenges are frequently encountered.

Multimodality treatment of intracranial dural arteriovenous fistulas in the Onyx era: a single center experience.

BACKGROUND The results of treatment of intracranial dural arteriovenous fistulas (DAVFs) since Onyx became available as an embolic agent at our institution is reported. An algorithm is presented for treatment of DAVFs with Onyx, and the role of endovascular transvenous, surgical, and radiosurgical approaches are presented. METHODS Thirty-two patients with DAVFs treated between November 2005 and November 2008 by endovascular embolization, surgery, or radiosurgery were identified by a retrospective chart review. Treatment strategies were based on the location or complexity of the fistula and the patients clinical status. Data collected included DAVF characteristics, obliteration rates, complications, and outcomes. The results were analyzed and correlated with the treatment modality. RESULTS Presenting symptoms were as follows: hemorrhage (n = 12 patients), headaches (n = 12), tinnitus (n = 5), orbital symptoms (n = 7), and seizures (n = 1). Thirty patients were treated by endovascular embolization (transarterial only with Onyx-21, transvenous only with platinum coils-6, transarterial [Onyx] and transvenous [coils]-3). Five patients (4 after incomplete/failed embolization) had surgical excision of the fistula. Three patients were treated with Gamma Knife radiosurgery (primary-1, 2 after incomplete/failed embolization). The locations of the fistulas were transverse sigmoid (10 patients), petrotentorial (7 patients), indirect carotid cavernous fistula (7 patients), parasagittal/falcine (3 patients), middle fossa dura (3 patients), torcula (1 patient), and anterior fossa dura (1 patient). The distribution of patients according to Borden classification was I-6, II-13, and III-13. Complete obliteration of the fistula was achieved in 26/32 (81%) patients after multimodal treatment. All surgical cases had complete obliteration. In the high-risk group with cortical venous reflux, 23/26 (89%) patients were cured. Endovascular complications included a stuck microcatheter tip with fracture of the tip in two patients and cranial nerves V and VII palsies in one patient. At last follow-up (range 1-36 months), 24 patients had modified Rankin score of 0-2, 5 patients had modified Rankin score of 3-5, and 3 patients were dead. Two patients died during admission due to the insult of the hemorrhage, and one died after an accidental fall with subsequent traumatic subdural hematoma. CONCLUSIONS Multimodality treatment of DAVFs has high success rates for cure at our center. Transarterial embolization with Onyx has become the primary treatment for intracranial DAVFs at our center and is associated with high safety profile and efficacy. Transvenous coil embolization is still preferred in DAVFs with supply from arterial branches supplying cranial nerves, predominant internal carotid artery feeders and potential extracranial-intracranial collateral anastomosis. In our series, patients with incompletely treated DAVFs were treated with surgery and those with partially treated type I fistulas had radiosurgery for palliation.

Postembolization neurological deficits in cerebral arteriovenous malformations: stratification by arteriovenous malformation grade.

OBJECTIVE To stratify the risk of embolization during the treatment of cerebral arteriovenous malformations (AVMs) by grade and to assess its impact on the overall treatment risk. METHODS Patients with cerebral AVMs treated with embolization between 1995 and 2004 were retrospectively reviewed. Age, sex, AVM grade, location of lesion, number and location of embolized arteries, and number of embolization sessions were analyzed with respect to neurological or vascular complications after embolization. RESULTS Embolization was performed in 153 patients: 508 vessels were embolized during 203 sessions (mean, 3.3 vessels per patient). The mean angiographic and clinical follow-up periods were 1.7 and 2.1 years, respectively (range, 3-60 mo). The periprocedural morbidity and mortality rate was 11.8%, but at the last follow-up examination, only 2% of survivors were significantly disabled (modified Rankin score > 2). One (0.7%) patient died, and 17 patients experienced unexpected neurological deficits immediately after embolization. Five of these patients demonstrated near or total recovery during follow-up. The number of branches embolized was the only variable significantly related to neurological deficit (P < 0.017). The long-term rates of neurological deficits after embolization were 0, 5, 7, 10, and 18%, respectively, for AVM Grades I through V. Among 114 patients who underwent preoperative embolization, follow-up deficit rates of Grades I through V were 0, 5, 6, 6, and 25%, respectively. Long-term permanent deficits from embolization occurred in 8.6% of patients. CONCLUSION Endovascular treatment carries a procedural risk related to AVM grade and number of branches treated. This risk should be weighed carefully in the context of overall treatment morbidity and mortality.

Surgical risks associated with the management of Grade I and II brain arteriovenous malformations.

OBJECTIVE Grade I and II arteriovenous malformations (AVMs) have been considered safe to resect. However, unoperated low-grade AVMs have not been considered in previously reported series. The aim of this study was to examine all cases, both operated and unoperated, to identify any characteristics of low-grade AVMs that comprise a subgroup that might pose a relatively higher risk. METHODS A prospectively enrolled AVM database included 237 patients in Spetzler-Martin Grade I or II. These patients were analyzed on the basis of demographic characteristics, angiographic and magnetic resonance imaging features, clinical presentation, method of treatment, and outcome. RESULTS Surgery was performed in 220 patients in Spetzler-Martin Grade I or II. Seventeen patients did not undergo treatment because of poor neurological condition (six patients), patient refusal (nine patients), and perceived surgical difficulty (AVM size approaching 3 cm adjacent to Brocas area) (two patients). The overall surgical morbidity rate was 0.9%, and the mortality rate was 0.5%. Adverse outcomes occurred in 1 (0.6%) of 180 patients with AVMs located away from eloquent cortex and in 2 (5%) of 40 patients with AVMs adjacent to eloquent cortex. None of 28 surgical patients with deep venous drainage had an adverse outcome. All 219 patients who survived surgery underwent postoperative angiography that confirmed cure. No postoperative hemorrhage has occurred in 1143 patient-years of follow-up (mean follow-up, 5.3 yr). CONCLUSION When considering adverse outcome in the surgical series of Grade I and II AVMs alone, no statistical difference between non-eloquently located AVMs (0.6%) and eloquently located AVMs (5% adverse outcome) can be detected. However, consideration of all Grade I and II AVMs, both surgical and nonsurgical, may prove that a difference in outcome exists between these two groups masked by case selection. Generalization of the chances of adverse outcomes to all Grade I and II AVMs (both operated and unoperated) suggests that the risk of performing surgery on noneloquent brain in our series was 0.6% and that in eloquent brain could have been as high as 9.5%, had all such patients undergone surgery.

Unruptured Cerebral Aneurysms Do Not Shrink When They Rupture: Multicenter Collaborative Aneurysm Study Group

BACKGROUND:The International Study of Intracranial Aneurysms found that for patients with no previous history of subarachnoid hemorrhage, small (< 7 mm) anterior circulation and posterior circulation aneurysms had a 0% and 2.5% risk of subarachnoid hemorrhage over 5 years, respectively. OBJECTIVE:To determine whether cerebral aneurysms shrink with rupture. METHODS:The clinical databases of 7 sites were screened for patients with imaging of cerebral aneurysms before and after rupture. Inclusion criteria included documented subarachnoid hemorrhage by imaging or lumbar puncture and intracranial imaging before and after cerebral aneurysm rupture. The patients were evaluated for aneurysm maximal height, maximal width, neck diameter, and other measurement parameters. Only a change of ≥ 2 mm was considered a true change. RESULTS:Data on 13 patients who met inclusion criteria were collected. The median age was 60, and 11 of the 13 patients (84.6%) were female. Only 5 patients had posterior circulation aneurysms. None of the aneurysms had a significant decrease in size. One aneurysm decreased by 1.8 mm in maximum size after rupture (7.7%). Six aneurysms had an increase in maximum size of at least 2 mm after rupture (46.2%) with a mean increase of 3.5 mm (± 0.5 mm). CONCLUSION:Unruptured aneurysms do not shrink when they rupture. The large percentage of ruptured small aneurysms in previous studies were likely small before they ruptured.