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Yu-ichiro Ohnishi, Koichi Iwatsuki, Masahiro Ishihara, Toshika Ohkawa, Manabu Kinoshita, Koei Shinzawa, Yasunori Fujimoto and Toshiki Yoshimine

OBJECTIVE

Diffuse astrocytomas (DAs) have a high recurrence rate due to diffuse infiltration into the brain and spinal cord. Micro RNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been reported that miRNA-22 (miR-22) is involved in the invasion of some cancer cell lines. The aim of this study was to identify the biological effects of miR-22 in regard to the invasion of human DAs.

METHODS

The authors evaluated whether the level of miR-22 is elevated in human spinal DAs by using miRNA chips. Next, the role of miR-22 in 1321N1 human astrocytoma cells was investigated. Finally, to elucidate whether miR-22 promotes invasion by astrocytoma cells in vivo, the authors transplanted miR-22 overexpressed astrocytoma cells into mouse thoracic spinal cord.

RESULTS

The miR-22 significantly upregulated the invasion capacity of 1321N1 cells. Computational in silico analysis predicted that tissue inhibitor of matrix metalloproteinase–2 (TIMP2) is a target gene of miR-22. This was confirmed by quantitative reverse transcription polymerase chain reaction and Western blotting, which showed that miR-22 inhibited TIMP2 mRNA and protein expression, respectively. Luciferase reporter assays demonstrated that miR-22 directly bound the 3′-untranslated regions of TIMP2. The authors further showed that miR-22 promoted invasiveness in 1321N1 astrocytoma cells when transplanted into mouse spinal cord.

CONCLUSIONS

These data suggest that miR-22 acts to regulate invasion of 1321N1 astrocytoma cells by targeting TIMP2 expression. Additional studies with more cases and cell lines are required to elucidate the findings of this study for a novel treatment target for spinal DAs.

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Hidetoshi Matsukawa, Hiroyasu Kamiyama, Toshiyuki Tsuboi, Kosumo Noda, Nakao Ota, Shiro Miyata, Takanori Miyazaki, Yu Kinoshita, Norihiro Saito, Osamu Takahashi, Rihee Takeda, Sadahisa Tokuda and Rokuya Tanikawa

OBJECTIVE

Only a few previous studies have investigated subarachnoid hemorrhage (SAH) after surgical treatment in patients with unruptured intracranial aneurysms (UIAs). Given the improvement in long-term outcomes of embolization, more extensive data are needed concerning the true rupture rates after microsurgery in order to provide reliable information for treatment decisions. The purpose of this study was to investigate the incidence of and risk factors for postoperative SAH in patients with surgically treated UIAs.

METHODS

Data from 702 consecutive patients harboring 852 surgically treated UIAs were evaluated. Surgical treatments included neck clipping (complete or incomplete), coating/wrapping, trapping, proximal occlusion, and bypass surgery. Clippable UIAs were defined as UIAs treated by complete neck clipping. The annual incidence of postoperative SAH and risk factors for SAH were studied using Kaplan-Meier survival analysis and Cox proportional hazards regression models.

RESULTS

The patients’ median age was 64 years (interquartile range [IQR] 56–71 years). Of 852 UIAs, 767 were clippable and 85 were not. The mean duration of follow-up was 731 days (SD 380 days). During 1708 aneurysm years, there were 4 episodes of SAH, giving an overall average annual incidence rate of 0.23% (95% CI 0.12%–0.59%) and an average annual incidence rate of 0.065% (95% CI 0.0017%–0.37%) for clippable UIAs (1 episode of SAH, 1552 aneurysm-years). Basilar artery location (adjusted hazard ratio [HR] 23, 95% CI 2.0–255, p = 0.0012) and unclippable UIA status (adjusted HR 15, 95% CI 1.1–215, p = 0.046) were significantly related to postoperative SAH. An excellent outcome (modified Rankin Scale score of 0 or 1) was achieved in 816 (95.7%) of 852 cases overall and in 748 (98%) of 767 clippable UIAs at 12 months.

CONCLUSIONS

In this large case series, microsurgical treatment of UIAs was found to be safe and effective. Aneurysm location and unclippable morphologies were related to postoperative SAH in patients with surgically treated UIAs.

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Hidetoshi Matsukawa, Hiroyasu Kamiyama, Takanori Miyazaki, Yu Kinoshita, Nakao Ota, Kosumo Noda, Takaharu Shonai, Osamu Takahashi, Sadahisa Tokuda and Rokuya Tanikawa

OBJECTIVE

Perforator territory infarction (PTI) is still a major problem needing to be solved to achieve good outcomes in aneurysm surgery. However, details and risk factors of PTI diagnosed on postoperative MRI remain unknown. The authors aimed to investigate the details of PTI on postoperative diffusion-weighted imaging (DWI) in patients with surgically treated unruptured intracranial saccular aneurysms (UISAs).

METHODS

The data of 848 patients with 1047 UISAs were retrospectively evaluated. PTI was diagnosed on DWI, which was performed the day after aneurysm surgery. Clinical and radiological characteristics were compared between UISAs with and without PTI. Poor outcome was defined as an increase in 1 or more modified Rankin Scale scores at 12 months after aneurysm surgery.

RESULTS

Postoperative DWI was performed in all cases, and it revealed PTI in 56 UISA cases (5.3%). Forty-three PTIs occurred without direct injury and occlusion of perforators (43 of 56, 77%). Poor outcome was more frequently observed in the PTI group (17 of 56, 30%) than the non-PTI group (57 of 1047, 5.4%) (p < 0.0001). Thalamotuberal arteries (p < 0.01), lateral striate arteries (p < 0.01), Heubner’s artery (p < 0.01), anterior median commissural artery (p < 0.05), terminal internal carotid artery perforators (p < 0 0.01), and basilar artery perforator (p < 0 0.01) infarctions were related to poor outcome by adjusted residual analysis. On multivariate analysis, statin use (OR 10, 95% CI, 3.3–31; p < 0.0001), specific aneurysm locations (posterior communicating artery [OR 4.1, 95% CI 2.1–8.1; p < 0.0001] and basilar artery [OR 3.1, 95% CI 1.1–8.9; p = 0.031]), larger aneurysm size (OR 1.1, 95% CI 1.1–1.2; p = 0.043), and permanent decrease of motor evoked potential (OR 38, 95% CI 3.1–468; p = 0.0045) were related to PTI.

CONCLUSIONS

Despite efforts to avoid PTI, it occurred even without direct injury, occlusion of perforators, or evoked potential abnormality. Therefore, surgical treatment of UISAs, especially with the aforementioned risk factors of PTI, should be more carefully considered. The evaluation of PTI in the territory of the above-mentioned perforators could be useful in helping predict the clinical course in patients after aneurysm surgery.

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Hidetoshi Matsukawa, Hiroyasu Kamiyama, Yu Kinoshita, Norihiro Saito, Yuto Hatano, Takanori Miyazaki, Nakao Ota, Kosumo Noda, Takaharu Shonai, Osamu Takahashi, Sadahisa Tokuda and Rokuya Tanikawa

OBJECTIVE

It is well known that larger aneurysm size is a risk factor for poor outcome after surgical treatment of unruptured saccular intracranial aneurysms (USIAs). However, the authors have occasionally observed poor outcome in the surgical treatment of small USIAs and hypothesized that size ratio has a negative impact on outcome. The aim of this paper was to investigate the influence of size ratio on outcome in the surgical treatment of USIAs.

METHODS

Prospectively collected clinical and radiological data of 683 consecutive patients harboring 683 surgically treated USIAs were evaluated. Dome-to-neck ratio was defined as the ratio of the maximum width of the aneurysm to the average neck diameter. The aspect ratio was defined as the ratio of the maximum perpendicular height of the aneurysm to the average neck diameter of the aneurysm. The size ratio was calculated by dividing the maximum aneurysm diameter (height or width, mm) by the average parent artery diameter (mm). Neurological worsening was defined as an increase in modified Rankin Scale score of 1 or more points at 12 months. Clinical and radiological variables were compared between patients with and without neurological worsening.

RESULTS

The median patient age was 64 years (IQR 56–71 years), and 528 (77%) patients were female. The median maximum size, dome-to-neck ratio, aspect ratio, and size ratio were 4.7 mm (IQR 3.6–6.7 mm), 1.2 (IQR 1.0–1.4), 1.0 (IQR 0.76–1.3), and 1.9 (IQR 1.4–2.8), respectively. The size ratio was significantly correlated with maximum size (r = 0.83, p < 0.0001), dome-to-neck ratio (r = 0.69, p < 0.0001), and aspect ratio (r = 0.74, p < 0.0001). Multivariate logistic regression analysis showed that the specific USIA location (paraclinoid segment of the internal carotid artery: OR 6.2, 95% CI 2.6–15, p < 0.0001; and basilar artery: OR 8.4, 95% CI 2.8–25, p < 0.0001), size ratio (OR 1.3, 95% CI 1.1–1.6, p = 0.021), and postoperative ischemic lesion (OR 9.4, 95% CI 4.4–19, p < 0.0001) were associated with neurological worsening (n = 52, 7.6%), and other characteristics showed no significant differences.

CONCLUSIONS

The present study showed that size ratio, and not other morphological parameters, was a risk factor for 12-month neurological worsening in surgically treated patients with USIAs. The size ratio should be further studied in a large, prospective observational cohort to predict neurological worsening in the surgical treatment of USIAs.