Two weeks administration of tranexamic acid for acute intracerebral hemorrhage: A hospital-based pilot study.

Background: A previous report suggested that functional status does not differ between patients who received tranexamic acid and those who received placebo within the early hours of intracerebral hemorrhage (ICH). Our pilot study tested the hypothesis that 2 weeks administration of tranexamic acid would contribute to functional improvement. Methods: Consecutive patients with ICH were administered 250 mg tranexamic acid 3 times a day continuously for 2 weeks. We also enrolled historical control consecutive patients. We collected clinical data that involved hematoma size, level of consciousness, and Modified Rankin Scale (mRS) scores. Results: Univariate analysis showed that the mRS score on day 90 was better in the administration group (P = 0.0095). The mRS scores on the day of death or discharge suggested a favorable effect of the treatment (P = 0.0678). Multivariable logistic regression analysis also showed that the treatment was associated with good mRS scores on day 90 (odds ratio [OR] = 2.81, 95% confidence interval [CI]: 1.10-7.21, P = 0.0312). In contrast, ICH size was associated with poor mRS scores on day 90 (OR = 0.92, 95% CI: 0.88-0.97, P = 0.0005). After propensity score matching, there was no difference in the outcomes between the two groups. We did not detect mild and serious adverse events. Conclusion: The study could not show the significant effect of 2 weeks administration of tranexamic acid on functional outcomes of ICH patients after the matching; however, suggested that this treatment is at least safe and feasible. A larger and adequately powered trial is needed.

Clipping on Crossed Wrapping Method for Ruptured Blood Blister-Like Aneurysm of the Internal Carotid Artery: Technical Note and Long-Term Results.

BACKGROUND: We have been performing the clipping on crossed wrapping (COCW) method using 2 strips of cotton on patients with an internal carotid artery blood blister-like aneurysm (IC-BLA). This method is reliable in preventing the clips from slipping off and the aneurysm walls from being damaged during clipping, and it enables more appropriate and safer clipping. Here we report the technical details of this method and the long-term outcomes of patients receiving this procedure. METHODS: Fifteen of 1275 (1.5%) patients with a ruptured cerebral aneurysm who received treatment at the Saiseikai Kumamoto Hospital during the period from January 1, 1999, to December 31, 2016, had an IC-BLA. All 15 patients were treated with COCW, except for the first patient, who was treated using a single strip of cotton. The long-term outcome of the treatment was analyzed. RESULTS: The mean follow-up period was 74 months. The first patient experienced rerupture of an aneurysm 10 days after the operation. No complications or regrowth of an aneurysm were observed in the remaining 14 patients during the follow-up period, except for 1 patient who received a reoperation for the regrowth of an aneurysm. As the final outcome, the numbers of patients with a Modified Rankin Score of 0, 3, and 6 were 13, 1, and 1, respectively. CONCLUSIONS: It is suggested that COCW is a treatment that enables safe and long-term management of lesions in IC-BLAs.

A new type of hyperplastic anterior choroidal artery.

Hyperplastic anomaly of the anterior choroidal artery (hyperplastic AchA) and posterior communicating artery of duplicate origin (duplicated Pcom) are rare vessel anomalies. With some literature review, we here report three cases of hyperplastic AchA, one of which was considered a new type of hyperplastic AchA. This case was not categorized into Takahashi classification.

Prolonged Mean Transit Time Detected by Dynamic Susceptibility Contrast Magnetic Resonance Imaging Predicts Cerebrovascular Reserve Impairment in Patients with Moyamoya Disease.

BACKGROUND: Evaluating cerebrovascular reserve (CVR) is important for patients with moyamoya disease (MMD). 123I-iodoamphetamine single-photon emission CT (SPECT) with acetazolamide (ACZ) challenge is widely carried out, but using ACZ becomes problematic owing to its off-label use and its adverse effects. Here, we report the efficacy of dynamic susceptibility contrast MRI (DSC-MRI) for the evaluation of CVR in MMD patients. METHODS: All 33 MMD patients underwent both SPECT and DSC-MRI at an interval of <10 days from each other (mean age 38.3 years). The region of interest (ROI) was the anterior cerebral artery (ACA) territory, middle cerebral artery (MCA) territory, basal ganglia and cerebellum hemisphere for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) images. The ratios of the ROIs to the ipsilateral cerebellum were calculated for each parameter and evaluated. The CVR was calculated using images acquired by SPECT before and after ACZ administration. The ratios of DSC-MRI parameters and CVR were compared and evaluated for each ROI. RESULTS: The MTT of the ACA and MCA territories significantly correlated with CVR (p < 0.0001). However, CBF and CBV had no correlation with CVR. The MTT ratio had a threshold of 1.966, with a sensitivity of 68.4% and a specificity of 91.5% for predicting decreased CVR (<10%). CONCLUSION: MTT had a negative correlation with CVR. DSC-MRI is easy, safe and useful for detecting decreased CVR and can be used as a standard examination in MMD patient's care.

Superficial temporal artery-to-middle cerebral artery bypass surgery for middle cerebral artery stenosis in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a rare hereditary small vessel disease. Ischemic events are the main clinical manifestation of this condition. Here, we present a case in which superficial temporal artery-to-middle cerebral artery anastomosis was performed in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy who developed cerebral infarctions caused by severe middle cerebral artery stenosis. Cerebral blood flow and cerebrovascular reactivity were effectively improved using double anastomoses. To our knowledge, surgical revascularization for patients with this condition has not yet been described in the literature. Superficial temporal artery-to-middle cerebral artery anastomosis is effective for patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy who show marked regional cerebral hypoperfusion.

Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients.

BACKGROUND: To determine the prognostic value of isocitrate dehydrogenase 1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and 1p/19q co-deletion in Japanese patients with malignant gliomas. METHODS: We studied 267 malignant gliomas, which included 171 glioblastomas (GBMs), 40 anaplastic astrocytomas (AAs), 30 anaplastic oligodendrogliomas (AOs), and 26 anaplastic oligoastrocytomas (AOAs). These malignant gliomas were divided into 2 groups (Group 1: GBM + AA, Group 2: AO + AOA) according to the presence of the oligodendroglioma component. We examined IDH1 mutation and MGMT promoter methylation in each group by direct sequencing and methylation-specific PCR, respectively. We further examined 1p/19q co-deletion in Group 2 by fluorescence in situ hybridization. Survival between groups was compared by Kaplan-Meier analysis. RESULTS: In Group 1, patients with IDH1 mutations exhibited a significantly longer survival time than patients with wild-type IDH1. However, no significant difference was observed in Group 2, although patients with IDH1 mutations tended to show prolonged survival. For both Group 1 and Group 2, patients with MGMT methylation survived longer than those without this methylation. Further, patients with 1p/19q co-deletion showed significantly better outcome in Group 2. CONCLUSIONS: Our study confirms the utility of IDH1 mutations and MGMT methylation in predicting the prognosis of Group 1 patients (GBM + AA) and demonstrated that IDH1 mutations may serve as a more reliable prognostic factor for such patients. We also showed that MGMT methylation and 1p/19q co-deletion rather than IDH1 mutations were prognostic factors for Group 2 patients (AOA + AO). Our study suggests that patients survive longer if they have IDH1 mutations and undergo total resection. Further, irrespective of MGMT promoter methylation status, the prognosis of glioma patients can be improved if total resection is performed. Moreover, our study includes the largest number of Japanese patients with malignant gliomas that has been analyzed for these three markers. We believe that our findings will increase the awareness of oncologists in Japan of the value of these markers for predicting prognosis and designing appropriate therapeutic strategies for treating this highly fatal disease.

Inhibition of eIF4E phosphorylation reduces cell growth and proliferation in primary central nervous system lymphoma cells.

The mRNA cap-binding protein eukaryotic initiation factor 4E (eIF4E) plays an important role in mRNA translation; its activity is implicated in cell growth and proliferation. In experimental models, eIF4E over-expression induces cellular transformation, tumorigenesis, and lymphomagenesis. The activity of eIF4E is regulated by the Akt/mTOR and MAPK/MAP kinase-interacting kinase-1 (MNK1) pathways. While investigating the participation of the MNK1/eIF4E signaling pathway in primary central nervous system lymphoma (PCNSL), we noted the over-expression of eIF4E and phosphorylated eIF4E (p-eIF4E) in specimens from PCNSL patients. Western blot analysis using B-cell lymphoma cell lines showed that eIF4E phosphorylation was serum-independent and was selectively inhibited by the MNK1 inhibitor. Furthermore, MNK1 inhibitor led to reduced cyclin D1 expression and caused inhibition of cell proliferation and cell death in human brain malignant lymphoma cell line (HKBML). Also, the growth of the subcutaneous HKBML xenografts in mice was inhibited by intraperitoneal administration of MNK1 inhibitor compared with mice treated with vehicle (P = 0.026). Our data suggest that in PCNSL cells eIF4E phosphorylation plays an important role in proliferation and our results identify inhibition of the MNK1/eIF4E pathway as a potential therapeutic target in patients with PCNSL.

Antitumor effect of humanized anti-interleukin-6 receptor antibody (tocilizumab) on glioma cell proliferation. Laboratory investigation.

OBJECT: Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates diverse physiological functions, including cell proliferation and survival. Recent studies have shown that IL-6 expression is often elevated in response to several types of glioma. Although IL-6 is said to play an important role in glioma, the involvement of IL-6 signaling has been quite controversial. The aim of this study was to evaluate the involvement of IL-6 signaling in glioma and the inhibitory effect of IL-6 signaling on glioma tumor proliferation. METHODS: The expression of IL-6 receptors (IL-6Rs) was evaluated in glioma tissues by means of immunohistochemical analysis, and the involvement of IL-6 signaling in glioblastoma multiforme (GBM) U87MG cell proliferation was also determined. In addition, to examine the inhibitory effect of IL-6 signaling on glioma cell proliferation, the authors investigated the effects of tocilizumab, the humanized anti-human IL-6R antibody in U87MG cells. RESULTS: Increased immunoreactivity for IL-6R was predominantly found in the cytoplasm of endothelial cells in all GBM samples. Inhibition of IL-6 signaling by both IL-6- and IL-6R-specific small interfering RNA and AG490, a specific inhibitor of JAK2 phosphorylation, suppressed glioma cell proliferation. Furthermore, tocilizumab, a clinically developed humanized anti-human IL-6R antibody, exerted an antiproliferative effect on cells from the GBM cell line U87MG via the IL-6R-dependent JAK-STAT3 pathway. CONCLUSIONS: The IL-6 signaling pathway plays an important role in glioma cell proliferation, and tocilizumab exerts an antitumor effect in U87MG glioma cells. These results may bring new insight into the molecular pathogenesis of glioma and may lead to a new therapeutic intervention.

Postoperative quality of life of patients treated for asymptomatic unruptured intracranial aneurysms.

OBJECT: The aim of this study was to assess the quality of life (QOL) of patients who underwent surgery for asymptomatic unruptured intracranial aneurysms (UIAs). METHODS: The authors assessed QOL in 149 patients who had undergone microsurgical clipping of asymptomatic UIAs. They surveyed these patients using universal methods such as the 36-Item Short Form Health Survey (SF-36) for health-related QOL and the Hospital Anxiety and Depression Scale for anxiety and depression assessments. RESULTS: The patients' mean scores for each of the eight domains of SF-36 were comparable to those of a Japanese reference population. Analysis of data from the average-QOL and low-QOL subgroups showed that the low-QOL group contained a higher number of patients with preexisting heart diseases and restricted activities of daily living. Operative procedures and complications did not affect QOL. CONCLUSIONS: Because 86% of the patients who underwent surgery manifested a QOL similar to the reference population, the authors suggest that elective surgery for asymptomatic UIAs is a reasonable treatment, especially in patients who are troubled by the risk of rupture. Postoperative decreases in QOL are not invariably attributable to the operation or its associated complications, but may be correlated with other chronic disorders. To select the appropriate treatment for asymptomatic UIAs, neurosurgeons and patients need information on the expected postoperative QOL.

[Self-assesed quality of life in patients who underwent surgery for asymptomatic meningiomas].

The aim of our study was to assess the quality of life (QOL) of patients operated on for asymptomatic meningioma and to assess the correlation between QOL and operative complications. Of 21 surgically treated patients, 6 (28.6%) presented with persistent neurological impairments or events considered to be treatment-related. Seventeen patients participated in the QOL survey using MOS Short-Form 36-Item Health Survey (SF-36) for health-related QOL issues and the Hospital Anxiety and Depression Scale (HADS) for anxiety nd depression assessment. The mean scores for each of the 8 domains of SF-36 were comparable with these of a Japanese reference population. When we divided the patients into 2 groups according to the degree of headache, activity of daily living, or complications, the QOL of patients with persistent headache declined in the SF-36 domains related to physical function and vitality. Minor neurological impairments developed by 4 patients did not affect their QOL. In conclusion, surgery for asymptomatic meningioma has no negative impact on postoperative QOL if the surgical complications are minor. On the other hand, physical activities in some patients were hampered due to persistent headache. Besides the treatment-related morbidity and mortality rates, QOL issues should also be included in treatment indications for asymptomatic meningioma.

Improvement of quality of life in patients surgically treated for asymptomatic unruptured intracranial aneurysms.

OBJECTIVE: To compare the preoperative and postoperative health-related quality of life (QOL) and psychological state of patients with asymptomatic unruptured intracranial aneurysms (ICAs) who underwent elective surgery. METHODS: Out of 67 patients who underwent neck clipping of ICAs, we assessed the QOL of 61 patients using Short Form-36 (SF-36); their psychological state was rated on the Hospital Anxiety and Depression Scale (HADS) before, 3 months, and 1 and 3 years after treatment. RESULTS: The preoperative mean scores for each of the eight SF-36 domains except bodily pain were significantly lower in the study population than in the reference population. 14 (20.9%) patients experienced surgical complications defined as neurological deterioration and/or abnormal CT findings within 30 days of the operation. Despite some complications, the QOL of all operated patients returned to the mean level of the reference population 3 years after treatment. At 3 months after surgery, the scores for psychosocial activities and general health perception were transiently below the preoperative levels. According to the HADS, the patients experienced mild anxiety before the operation; it disappeared by the third postoperative month. CONCLUSIONS: Preoperatively, patients with unruptured ICAs reported a significantly decreased QOL. It further declined transiently after elective surgery, but it returned to the mean level recorded for the reference population within 3 years. Our findings suggest that these patients derived significant QOL benefits from their surgery. Hence subjective QOL issues should be considered in deciding whether treatment-related risks and their natural history, such as their potential rupture, warrant surgery of asymptomatic unruptured ICAs.

Cavernous malformation of the optic chiasm: case report.

We report a 14-year-old boy with cavernous malformation of the optic chiasm. He had a 2-year history of gradually worsening visual disturbance. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a suprasellar mass, findings compatible with craniopharyngioma. The mass was biopsied and histological examination confirmed cavernous malformation. On the second day after the biopsy, he suffered chiasmal apoplexy due to intratumoural haemorrhage, lost visual acuity and developed a field cut. Cavernous malformations arising from the optic nerve and chiasm are extremely rare; only 29 cases have been reported to date. Most patients manifested acute visual acuity and visual field disturbances. Although MRI findings of cavernous malformations in the brain parenchyma have been reported, MRI findings on the optic nerve and chiasm may not be completely diagnostic. Of the 29 documented patients, 16 underwent total resection of the lesion without exacerbation of their preoperative symptoms; in some cases, resection was complicated by risk of damage to the surrounding neural tissue. As patients may suffer intratumoural haemorrhage after biopsy or partial removal of the lesion, the advisability of surgical treatment of cavernous malformations of the optic nerve and chiasm must be considered carefully.