Matrix metalloproteinase-9 (MMP-9) activation plays an important role in blood–brain barrier (BBB) dysfunction after central nervous system injury. Oxidative stress is also implicated in the pathogenesis after cerebral ischemia and spinal cord injury (SCI), but the relationship between MMP-9 activation and oxidative stress after SCI has not yet been clarified. We examined MMP-9 expression after SCI using copper/zinc–superoxide dismutase (SOD1) transgenic (Tg) rats. Our results show that MMP-9 activity significantly increased after SCI in both SOD1 Tg rats and their wild-type (Wt) littermates, although the increase was less in the SOD1 Tg rats. This pattern of MMP-9 expression was further confirmed by immunostaining and Western blot analysis. In situ zymography showed that gelatinolytic activity increased after SCI in the Wt rats, while the increase was less in the Tg rats. Evans blue extravasation increased in both the Wt and Tg rats, but was less in the SOD1 Tg rats. Inhibitor studies showed that, with an intrathecal injection of SB-3CT (a selective MMP-2/MMP-9 inhibitor), the MMP activity, Evans blue extravasation, and apoptotic cell death decreased after SCI. We conclude that increased oxidative stress after SCI leads to MMP-9 upregulation, BBB disruption, and apoptosis, and that overexpression of SOD1 in Tg rats decreases oxidative stress and further attenuates MMP-9 mediated BBB disruption.

Background: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. Methods: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0–1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. Results: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24–20.6]; P =0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P =0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62–30.7]; P =0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. Conclusions: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: UMIN000006640.

BACKGROUND AND PURPOSE: The incidence of wall enhancement of cerebral aneurysms on vessel wall MR imaging has been described as higher in ruptured intracranial aneurysms than in unruptured intracranial aneurysms, but the difference in the degree of enhancement between ruptured and unruptured aneurysms is unknown. We compared the degree of enhancement between ruptured and unruptured intracranial aneurysms by using quantitative MR imaging measures. MATERIALS AND METHODS: We performed quantitative analyses of circumferential enhancement along the wall of cerebral aneurysms in 28 ruptured and 76 unruptured consecutive cases by using vessel wall MR imaging. A 3D-T1-weighted fast spin-echo sequence was obtained before and after contrast media injection, and the wall enhancement index was calculated. We then compared characteristics between ruptured and unruptured aneurysms. RESULTS: The wall enhancement index was significantly higher in ruptured than in unruptured aneurysms (1.70 ± 1.06 versus 0.89 ± 0.88, respectively; P = .0001). The receiver operating characteristic curve analysis found that the most reliable cutoff value of the wall enhancement index to differentiate ruptured from unruptured aneurysms was 0.53 (sensitivity, 0.96; specificity, 0.47). The wall enhancement index remained significant in the multivariate logistic regression analysis (P < .0001). CONCLUSIONS: Greater circumferential enhancement along the wall of cerebral aneurysms correlates with the ruptured state. A quantitative evaluation of circumferential enhancement by using vessel wall MR imaging could be useful in differentiating ruptured from unruptured intracranial aneurysms.

Object: Internal coil trapping is a treatment method used to prevent rebleeding from a ruptured intracranial vertebral artery dissection (VAD). Postoperative medullary infarctions have been reported as a complication of this treatment strategy. The aim of this study was to determine the relationship between a postoperative medullary infarction and the clinical outcomes for patients with ruptured VADs treated with internal coil trapping during the acute stage of a subarachnoid hemorrhage (SAH). Methods: A retrospective study identified 38 patients who presented between 2006 and 2011 with ruptured VADs and underwent internal coil trapping during the acute stage of SAH. The SAH was identified on CT scanning, and the diagnosis for VAD was rendered by cerebral angiography. Under general anesthesia, the dissection was packed with coils, beginning at the distal end and proceeding proximally. When VAD involved the origin of the posterior inferior cerebellar artery (PICA) with a large cerebellar territory, an occipital artery (OA)–PICA anastomosis was created prior to internal coil trapping. The pre- and postoperative radiological findings, clinical course, and outcomes were analyzed. Results: The internal coil trapping was completed within 24 hours after admission. An OA-PICA anastomosis followed by internal coil trapping was performed in 5 patients. Postoperative rebleeding did not occur in any patient during a mean follow-up period of 16 months. The postoperative MRI studies showed medullary infarctions in 18 patients (47%). The mean length of the trapped VAD for the infarction group (15.7 ± 6.0 mm) was significantly longer than that of the noninfarction group (11.5 ± 4.3 mm) (p = 0.019). Three of the 5 patients treated with OA-PICA anastomosis had postoperative medullary infarction. The clinical outcomes at 6 months were favorable (modified Rankin Scale Scores 0–2) for 23 patients (60.5%) and unfavorable (modified Rankin Scale Scores 3–6) for 15 patients (39.5%). Of the 18 patients with postoperative medullary infarctions, the outcomes were favorable for 6 patients (33.3%) and unfavorable for 12 patients (66.7%). A logistic regression analysis predicted the following independent risk factors for unfavorable outcomes: postoperative medullary infarctions (OR 21.287 [95% CI 2.622–498.242], p = 0.003); preoperative rebleeding episodes (OR 7.450 [95% CI 1.140–71.138], p = 0.036); and a history of diabetes mellitus (OR 45.456 [95% CI 1.993–5287.595], p = 0.013). Conclusions: A postoperative medullary infarction was associated with unfavorable outcomes after internal coil trapping for ruptured VADs. Coil occlusion of the long segment of the VA led to medullary infarction, and an OA-PICA bypass did not prevent medullary infarction. A VA-sparing procedure, such as flow diversion by stenting, is an alternative treatment in the future, if this approach is demonstrated to effectively prevent rebleeding.

BACKGROUND: Identification of rupture sites in patients with multiple intracranial aneurysms is largely based on aneurysm size, location, and shape. Finding circumferential enhancement along the aneurysm wall (CEAW) on magnetic resonance (MR) vessel wall imaging was recently shown to be indicative of ruptured aneurysm. OBJECTIVE: To investigate the hypothesis that a higher degree of CEAW would identify the site of rupture in patients with multiple aneurysms. METHODS: We prospectively performed quantitative analysis of CEAW in consecutive patients with both aneurysmal subarachnoid hemorrhage and multiple aneurysms (26 patients with a total of 62 aneurysms), using MR vessel wall imaging. Three-dimensional T1-weighted fast spin-echo sequences were obtained before and after injection of contrast media, and the wall enhancement index (WEI) was calculated. Aneurysm characteristics (size, location, irregular shape, aspect ratio [neck-to-dome length/neck width], and WEI) were compared between ruptured and unruptured aneurysms. Odds ratios with 95% confidence intervals for ruptures were calculated with conditional univariable logistic regression analysis. Analyses were repeated after adjustment for aneurysm size. RESULTS: Large aneurysm size, high aspect ratio, WEI (above the median values), and irregular shape were significantly associated with aneurysm rupture. After adjustment for aneurysm size, WEI (adjusted odds ratio: 8.8; 95% confidence interval, 1.1-72.6) as well as irregular shape and aspect ratio showed a strong association with rupture. CONCLUSION: CEAW is associated with rupture of intracranial aneurysm independent of aneurysm size and patient characteristics. Contrast-enhanced MR vessel wall imaging helps to identify the site of rupture in patients with multiple aneurysms.

BACKGROUND AND PURPOSE: Ischemic complications after coil embolization of the PcomA aneurysms are not thoroughly understood, especially in cases in which the PcomA is sacrificed. Our purpose was to examine the preoperative angiographic features and pattern of postoperative cerebral infarctions exhibited by patients who underwent embolization of ruptured PcomA aneurysms with PcomA sacrifice. MATERIALS AND METHODS: A retrospective review identified 14 patients with ruptured PcomA aneurysms who underwent embolization of the aneurysms in combination with PcomA sacrifice. Preoperative angiographic data, including the Allcock test, postoperative DWI, and neurologic status, were examined. RESULTS: Elimination of the aneurysm was complete in all cases. Postoperative DWI indicated 7 cases with infarctions (infarction group) and 7 cases without infarctions (noninfarction group). All patients in the infarction group developed infarctions in the vicinity of the tuberothalamic artery. In all 14 cases, a preoperative Allcock test demonstrated a retrograde filling of the PcomA through the P1 segment. The incidence of negative visualizations of the P1 segment on vertebral angiograms was significantly higher in the infarction group (100%) than in the noninfarction group (0%; P = .00058). The mean PcomA diameters, PcomA/P1 ratios, and aneurysm sizes observed in the infarction group were significantly greater than those in the noninfarction group (P < .05, P < .01, and P < .02, respectively). Tuberothalamic artery infarction caused hemiparesis and memory disturbance, which were associated with unfavorable outcomes. CONCLUSIONS: After the coil occlusion of ruptured PcomA aneurysms with PcomA sacrifice, tuberothalamic artery infarctions tended to occur in cases exhibiting negative visualization of the P1 segment, even when collateral flow was observed with the Allcock test.