Joseph M. Zabramski

The Barrow Ruptured Aneurysm Trial

OBJECT The purpose of this ongoing study is to compare the safety and efficacy of microsurgical clipping and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to determine if one treatment is superior to the other by examining clinical and angiographic outcomes. The authors examined the null hypothesis that no difference exists between the 2 treatment modalities in the setting of subarachnoid hemorrhage (SAH). The current report is limited to the clinical results at 1 year after treatment. METHODS The authors screened 725 patients with SAH, resulting in 500 eligible patients who were enrolled prospectively in the study after giving their informed consent. Patients were assigned in an alternating fashion to surgical aneurysm clipping or endovascular coil therapy. Intake evaluations and outcome measurements were collected by nurse practitioners independent of the treating surgeons. Ultimately, 238 patients were assigned to aneurysm clipping and 233 to coil embolization. The 2 treatment groups were well matched. There were no anatomical exclusions. Crossing over was allowed, but primary outcome analysis was based on the initial treatment modality assignment. Posttreatment care was standardized for both groups. Patient outcomes at 1 year were independently assessed using the modified Rankin Scale (mRS). A poor outcome was defined as an mRS score > 2 at 1 year. The primary outcome was based on the assigned group; that is, by intent to treat. RESULTS One year after treatment, 403 patients were available for evaluation. Of these, 358 patients had actually undergone treatment. The remainder either died before treatment or had no identifiable source of SAH. A poor outcome (mRS score > 2) was observed in 33.7% of the patients assigned to aneurysm clipping and in 23.2% of the patients assigned to coil embolization (OR 1.68, 95% CI 1.08-2.61; p = 0.02). Of treated patients assigned to the coil group, 124 (62.3%) of the 199 who were eligible for any treatment actually received endovascular coil embolization. Patients who crossed over from coil to clip treatment fared worse than patients assigned to coil embolization, but no worse than patients assigned to clip occlusion. No patient treated by coil embolization suffered a recurrent hemorrhage. CONCLUSIONS One year after treatment, a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes than clip occlusion. Although most aneurysms assigned to the coil treatment group were treated by coil embolization, a substantial number crossed over to surgical clipping. Although a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes at 1 year, it remains important that high-quality surgical clipping be available as an alternative treatment modality.

CAVERNOUS MALFORMATIONS OF THE BRAIN STEM : A REVIEW OF 139 CASES

SummaryA retrospective analysis of 139 patients with brain stem cavernous malformations is presented. The material consists of 41 cases from Bern and Phoenix and 98 further well-documented cases from the literature. Sixty-eight patients were male, 70 were female. The average age was 31.8+11.8 years. Sixty-two percent of the cavernous malformations were in the pons, 14% were in the mesencephalon, 12% were in the pontomesencephalic and in the pontomedullary junction, and 5% were in the medulla. Eighty-eight percent of the patients showed evidence of recent or previous hemorrhage, 55% had one hemorrhage. 17% had two hemorrhages, and 17% had three or more hemorrhages. Twelve patients died from a hemorrhage, 5 with the first bleeding and 7 with a rebleeding. The minimum bleeding rate was 2.7% per year and the average rebleeding rate 21% per year and per lesion. Most lesions had a diameter between 10 and 30 mm. Increase in size was observed in 12 of the patients; this correspondends to about 21% when only patients with a follow-up of at least one year are considered. In 93 patients the cavernous malformation was removed operatively while in 30 patients the lesion was not removed. In the group with conservative management at the end of the observation period (up to 25 and 32 years), 66.6% had no or only a slight neurological deficit, 6.7% were moderately disabled, 6.7% were completely dependent, and 20% had died. In the group treated surgically 83.9% had no or only a slight neurological deficit, and 15% were moderately disabled. One patient remained severely disabled, no patient died. The limitations of the retrospective nature of this study are stressed.

The Efficacy and Cost of Prophylactic and Periprocedural Antibiotics in Patients with External Ventricular Drains

OBJECTIVEProphylactic antibiotics are routinely administered to patients with external ventricular drains (EVDs); however, no conclusive evidence supports this practice. This study compared the efficacy and cost of prophylactic and periprocedural antibiotics in patients with EVDs. METHODSWe reviewed the charts of 308 patients who had an EVD in place for 3 or more days between January 1996 and June 1997. Patients with EVDs placed for shunt infections or meningitis were excluded. A standard protocol was used to insert and monitor EVDs. Catheters were left in place as long as clinically indicated and changed only if they malfunctioned. Cerebrospinal fluid cultures were obtained twice weekly. Prophylactic antibiotics were used at the discretion of the attending neurosurgeon. Patients were divided into two groups: Group A comprised 209 patients who received prophylactic antibiotics for the duration of the EVD (intravenously administered cefuroxime, 1.5 g every 8 h); Group B comprised 99 patients who received only periprocedural antibiotics (intravenously administered cefuroxime, 1.5 g every 8 h, three or less doses). RESULTSAlthough there were significantly more males in Group A than in Group B, the two groups were otherwise well matched, with no significant differences in age, indications, or duration of EVD placement. The overall rate of ventriculitis was 3.9%. The infection rates for Group A (3.8%) and Group B (4.0%) were almost identical. CONCLUSIONProphylactic antibiotics did not significantly reduce the rate of ventriculitis in patients with EVDs, and they may select for resistant organisms. Discontinuing the use of prophylactic antibiotics for EVDs at the authors’ institution would save approximately

Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis

80,000 per year in direct drug costs.

Repair of vertebral artery injury during anterior cervical decompression.

Cerebral cavernous malformations (CCMs) are vascular anomalies of the central nervous system, comprising dilated blood-filled capillaries lacking structural support. The lesions are prone to rupture, resulting in seizures or hemorrhagic stroke. CCM can occur sporadically, manifesting as solitary lesions, but also in families, where multiple lesions generally occur. Familial cases follow autosomal-dominant inheritance due to mutations in one of three genes, CCM1/KRIT1, CCM2/malcavernin or CCM3/PDCD10. The difference in lesion burden between familial and sporadic CCM, combined with limited molecular data, suggests that CCM pathogenesis may follow a two-hit molecular mechanism, similar to that seen for tumor suppressor genes. In this study, we investigate the two-hit hypothesis for CCM pathogenesis. Through repeated cycles of amplification, subcloning and sequencing of multiple clones per amplicon, we identify somatic mutations that are otherwise invisible by direct sequencing of the bulk amplicon. Biallelic germline and somatic mutations were identified in CCM lesions from all three forms of inherited CCMs. The somatic mutations are found only in a subset of the endothelial cells lining the cavernous vessels and not in interstitial lesion cells. These data suggest that CCM lesion genesis requires complete loss of function for one of the CCM genes. Although widely expressed in the different cell types of the brain, these data also suggest a unique role for the CCM proteins in endothelial cell biology.

The Barrow Ruptured Aneurysm Trial: 6-year results.

Methods Vertebral artery injury is a rarely described complication of anterior cervical decompression. The authors performed a retrospective review of their operative database for the purposes of defining the optimal management of this complication and its avoidance. Results Four of 1,215 (0.3%) patients undergoing anteior cervical operation sustained arterial injuries. In three cases, primary repair of the artery was succesful; in one case, the artery was exposed and ligated. There were no postoperative ischemic compllcations. Artery laceration occurred during decompression (n=2), screw tapping (n=1), and during soft tissue retraction (n=1). Conclusions Injury to the vertebral artery during anterior approaches can be avoided by preoperative identification of anomalous arteries and by intraoperative attention to the midline. When the artery is injured, primary repair may be the optimal management strategy.

Outcome of oculomotor nerve palsy from posterior communicating artery aneurysms: comparison of clipping and coiling.

OBJECT The authors report the 6-year results of the Barrow Ruptured Aneurysm Trial (BRAT). This ongoing randomized trial, with the final goal of a 10-year follow-up, compares the safety and efficacy of surgical clip occlusion and endovascular coil embolization in patients presenting with subarachnoid hemorrhage (SAH) from a ruptured aneurysm. The 1- and 3-year results of this trial have been previously reported. METHODS In total, 500 patients with an SAH met the entry criteria and were enrolled in the study. Of these patients, 471 were randomly assigned to the treatments: 238 to surgical clipping and 233 to endovascular coiling. Six patients who died before treatment and 57 patients with nonaneurysmal SAHs were excluded, leaving a total of 408 patients who underwent clipping (209 assigned) or coiling (199 assigned). Whether to treat patients within the assigned group or to cross over patients to the other group was at the discretion of the treating physician; 38% (75/199) of the patients assigned to coiling were crossed over to clipping and 1.9% (4/209) assigned to clipping were crossed over to coiling. The outcome data were collected by a dedicated nurse practitioner. The primary outcome analysis was based on the assigned treatment group; poor outcome was defined as a modified Rankin Scale (mRS) score > 2 and was independently adjudicated. Six years after randomization, 336 (82%) of 408 patients who had been treated were available for examination. RESULTS On the basis of an mRS score of > 2, and similar to the results at the 3-year follow-up, no significant difference in outcomes (p = 0.24) was detected between the 2 treatment groups. Complete aneurysm obliteration at 6 years was achieved in 96% (111/116) of the clipping group and in 48% (23/48) of the coiling group (p < 0.0001). In the period between the 3- and 6-year follow-ups, 3 additional patients assigned to coiling and none assigned to clipping received retreatment, for overall retreatment rates of 4.6% (13/280) for clipping and 16.4% (21/128) for coiling (p < 0.0001). When aneurysm location was considered, the 6-year results continued to match the previously reported results, with no difference in outcome for anterior circulation aneurysms at most time points. Of the anterior circulation aneurysms assigned to coiling treatment, 42% (70/168) were crossed over to clipping treatment. The outcomes for posterior circulation aneurysms continued to favor coiling. The randomization process was unexpectedly skewed, with 18 of 21 treated aneurysms of the posterior inferior cerebellar artery (PICA) being assigned to clipping, but even when PICA aneurysms were removed from the analysis, outcomes for the posterior circulation aneurysms still favored coiling. CONCLUSIONS Although BRAT was statistically underpowered to detect small differences, these results suggest little difference in outcome between the 2 treatments for anterior circulation aneurysms. This was not the case for the posterior circulation aneurysms, where coil embolization appeared to provide a sustained advantage over clipping. Aneurysm obliteration rates in BRAT were significantly lower and retreatment rates significantly higher in the patients undergoing coiling than in those undergoing clipping. However, despite the fact that retreatment rates were higher after coiling, no recurrent hemorrhages were known to have occurred in patients undergoing coiling in BRAT who were followed up for 6 years. Sufficient questions remain about the relative benefits of the 2 treatment modalities to warrant further well-designed randomized trials.

Pediatric spinal cord injury without radiographic abnormalities: report of 26 cases and review of the literature.

OBJECTIVE:Recovery of posterior communicating artery aneurysm-induced oculomotor nerve palsy (ONP) after aneurysm coiling has been reported. However, the coil mass may compromise recovery of the nerve. Therefore, we compared the outcome of coiling and clipping for this indication. METHODS:We retrospectively compared the outcomes of ONP in 13 patients, six of whom underwent endovascular coiling and seven of whom underwent surgical clipping. RESULTS:Six of the seven surgical patients with ONP recovered completely, compared with two of the six patients in the endovascular group. Of the patients with more than 1 year of follow-up, all six surgical patients recovered completely, compared with two of four endovascular patients (P = 0.05). In addition, preoperative complete or partial ONP also was associated with degree of resolution by survival analysis (P = 0.03). All patients with partial ONP in the surgical group and two of three patients in the endovascular group recovered without residual deficits, whereas three of the four patients with complete ONP in the clipping group and none in the coiling group recovered completely. Regardless of the treatment method, time to complete resolution of ONP was 6 months in both groups. CONCLUSION:Clipping posterior communicating artery aneurysms was associated with a higher probability of complete recovery from ONP than coiling. Degree of preoperative ONP also affected recovery. If patients can tolerate surgery, it should be considered the treatment of choice.

Chronic cerebral vasospasm: effect of volume and timing of hemorrhage in a canine model

Spinal cord injury without radiographic abnormality (SCIWORA) occurs primarily in the pediatric population but is less common than other forms of spinal injury among children. Between 1972 and 1990, 159 pediatric patients were admitted to the Barrow Neurological Institute with acute traumatic spinal cord or vertebral column injuries. Of these, 26 children (16%) sustained SCIWORA. The mechanism of injury, its severity, and the prognosis for recovery were related to the patients age. In young children, SCIWORA accounted for 32% of all spinal injuries and tended to be severe; 70% were complete injuries. In older children, SCIWORA accounted for only 12% of the spinal injuries, was rarely associated with a complete injury, and had an excellent prognosis for complete recovery of neurologic function. As with other types of spinal cord injuries, the severity of neurological injury was the most important predictor of outcome. Patients with complete neurological deficits from SCIWORA had a poor prognosis for recovery of neurological function.

Surgical treatment of high-risk intracranial dural arteriovenous fistulae: clinical outcomes and avoidance of complications.

The effect of altering the volume and timing of hemorrhage on the severity of spasm was studied in a canine model. All animals received three cisterna magna injections of fresh unheparinized autologous arterial blood. Selective left vertebral arteriograms were obtained during the week before and exactly 7 days after the initial subarachnoid injection. Increasing volumes of hemorrhage (from 9 to 15 ml of blood) delivered over 24 hours produced increasingly more severe arterial spasm, with reductions in basilar artery diameter of 37% +/- 14 (SD) and 58% +/- 15, respectively. Delay of the final injection of blood to 96 hours in the 15-ml hemorrhage group resulted in even more intense spasm, with an average 71% +/- 12 reduction in basilar artery diameter. Serial angiographic evaluation demonstrated the resolution of spasm in this group over approximately 3 weeks. Finally, small, late rebleeding episodes resulted in the rapid onset of intense spasm. Our results support the clinical impression of previous studies that the severity of spasm is related to the volume of hemorrhage and, in addition, suggest that the time course of hemorrhage may play a significant role in determining the overall severity of chronic cerebral vasospasm.