廣瀬 雄一

Objective High blood pressure (HBP) is observed frequently in patients with spontaneous intracerebral haemorrhage (SICH). Although HBP at admission has been associated with poor outcomes, most studies from which such conclusions were derived had been carried out decades earlier, when aggressive BP management was not implemented. In our institution, SICH patients showing HBP undergo aggressive BP management by intravenous nicardipine with target systolic BP (SBP) less than 140mmHg. We investigated whether responsiveness to intravenous nicardipine, haematoma expansion rate and activity of daily living 90 days after admission differed by the degree of admission SBP. Patients and methods A retrospective study was carried out by reviewing charts of 120 SICH patients admitted within 6 h of onset who were quadrichotomized on the basis of SBP: <140 mmHg (n=6), 140-184 mmHg (n=49), 185-219 mmHg (n=38) and >= 220 mmHg (n=27). The six patients with SBP less than 140 mmHg were excluded, and demographic and outcome variables of the latter three groups were compared. Whether plasma catecholamine levels differed among the three groups was also investigated. Results Optimal BP management (target SBP<140mmHg) within 2 h of arrival was achieved in 98%, haematoma expansion occurred in 7% and the 90-day mortality rate was 11%. Responsiveness to intravenous nicardipine, haematoma expansion rate and activity of daily living were not significantly different. Furthermore, plasma catecholamine levels did not differ significantly. Conclusion The lack of difference in the demographic and outcome variables in SICH patients managed by aggressive treatment to normalize the BP indicates that the previously reported association between HBP at admission and poor outcomes needs to be re-evaluated. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

AimTherapeutic intervention to repair unruptured aneurysms (UA) has not been strongly recommended for the elderly, because of their limited life expectancy and low annual bleeding rate. However, physically and mentally healthy older adults with seemingly high risk of aneurysmal bleeding might benefit from having their UA repaired. MethodsA single-center retrospective study was carried out. Among 1078 patients admitted for treatment of UA between 2007 and 2011, the number of patients aged 75 years who underwent surgical and endovascular repair of UA was 30 and 31, respectively. The operative and mid-term outcomes were compared between the two groups. For evaluation of the operative outcomes, frequency and types of adverse events that occurred within 30 days of intervention (operative morbidity) were described. For assessment of the mid-term outcomes, activities of daily living (ADL) at 24 months after intervention were evaluated with the modified Rankin Scale (mRS). ResultsThe operative morbidity rate was 6.7% in the open surgery group and 6.5% in the endovascular surgery group, and they did not differ significantly. The frequency of patients with mRS 0-2 at 24 months after intervention was 85.7% in the open surgery group and 82.8% in the endovascular surgery group, and they did not differ significantly. The adverse event rate of patients with middle cerebral artery aneurysms treated endovascularly was high (80%). ConclusionsThe outcomes of individuals aged 75 years who underwent repair of UA were generally favorable in either treatment group, with more than 80% living an independent life at 24 months after intervention. Geriatr Gerontol Int 2014; 14: 858-863.

Our assumption that blood pressure (BP) in supratentorial hypertensive intracerebral hemorrhage patients does not differ significantly according to the hemispheric laterality has never been verified before. This study was carried out to explore the possibility of hemispheric BP differences and whether this might influence the outcomes. A review of the charts/radiographic images of 281 patients with putaminal/thalamic hemorrhages diagnosed within 6 h of symptom onset was performed. Immediately after arrival, they received a continuous intravenous nicardipine infusion to lower and maintain systolic BP (SBP) between 120 and 160 mmHg. They were quadrichotomized as follows: left putamen (LP, n=89), right putamen (RP, n=69), left thalamus (LT, n=68), and right thalamus (RT, n=55). Two-group or four-group comparisons were made on demographic variables, BPs, and outcomes. Patients with left-sided hemorrhages presented with significantly worse neurologic scores in both hemorrhage categories and tended to sustain larger hematomas than their right-sided counterparts. Significant differences in SBPs between LP and RP (205 +/- 31 vs. 189 +/- 29 mmHg, P<0.01) as well as in diastolic BPs between LT and RT (109 +/- 19 vs. 97 +/- 20 mmHg, P=0.03) were noted. Multivariate regression analysis showed that patients with SBPs of at least 220 mmHg were 2.9 times more likely to harbor left-sided hemorrhages. There were no significant intergroup differences in responsiveness to a continuous intravenous nicardipine infusion or 30-day mortality rates. Although the differences in BPs are unlikely to have influenced outcomes, future trials involving supratentorial hypertensive intracerebral hemorrhages may benefit from considering hemispheric differences in BP and other demographic variables. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Background and Purpose Insular injuries are known to cause autonomic derangements. Patients with ruptured middle cerebral artery aneurysms frequently develop temporal hematomas (THs) in addition to subarachnoid hemorrhages, and those with TH may sustain autonomic derangements more frequently than those without TH. Hemispheric lateralization in autonomic derangements has been reported in patients with insular ischemic stroke, and this study was conducted to clarify whether such lateralization was also observed in patients with TH resulting from middle cerebral artery aneurysm rupture. Methods A retrospective analysis on the medical records of 79 patients with ruptured middle cerebral artery aneurysms was performed on the basis of lateralization and presence of TH. They were quadrichotomized as left TH+ (LTH+; n=17), right TH+ (n=25), left TH- (n=15), and right TH- (n=22). Comparisons, mainly between LTH+ and right TH+, were made on demographic variables, autonomic/cardiac parameters, plasma catecholamine and glucose levels, and outcomes. Results There were no significant differences in demographic or cardiac parameters between the 2 groups. Systolic blood pressures were lower in LTH+ (13934 versus 174 +/- 47 mm Hg; P=0.05). The LTH+ group also tended to be more bradycardiac (80 +/- 19 versus 101 +/- 22 bpm; P=0.13). The LTH+ group exhibited significantly lower plasma norepinephrine (1008 +/- 975 versus 2549 +/- 2133 pg/mL; P=0.03) and glucose levels (9.3 +/- 1.8 versus 12.2 +/- 4.5 mmol/L; P=0.04). However, in-hospital mortality did not differ significantly (41% versus 44%; P=1.00). Conclusions Lateralization of autonomic derangements observed might not have had a significant effect on the outcomes. Nevertheless, autonomic derangements associated with insular injury should be considered in the management of subarachnoid hemorrhage patients with TH.

Background: Malignant hemispheric infarction is a life-threatening condition with a high mortality rate. Decompressive hemicraniectomy (DHC) is frequently a life-saving procedure that has shown the highest grade of evidence for patients 18 to 60 years of age. However, the efficacy of DHC in patients >60 years of age has rarely been investigated. Methods: A retrospective study was conducted in a single academic institution. Surrogates of patients with clinical signs of impending brain herniation despite standard medical therapy were offered the option of DHC regardless of age or the side of the lesion. The clinical data from 18 patients >60 years of age who underwent DHC for malignant hemispheric infarction in our institution were analyzed. Patients were classified into the following 2 groups: 61-70 and >70 years of age, and their demographics and surgical outcomes were compared. The variables compared included the male: female ratio, side of the lesion, type of stroke, site of vascular occlusion, use of thrombolytic therapy, National Institutes of Health Stroke Scale score, stroke onset-to-DHC interval, duration of hospital stay, infectious complications, and 90-day mortality rate. Results: There were no significant intergroup differences in any of the demographic variables evaluated. However, the 30-day mortality rate was significantly higher in the group that was >70 years of age (0% v 60%; P = .01) than in the group that was 61 to 70 years of age. Conclusions: We suggest that the efficacy of DHC in malignant hemispheric stroke patients between 61 and 70 years of age be further investigated in future randomized trials. By contrast, it appears unlikely that patients >70 years of age would benefit from DHC.

The recent progress in chemotherapy for malignant gliomas is attributable to the introduction of the DNA-methylating agent temozolomide (TMZ) however, drug resistance remains a major issue. Previous studies have shown that TMZ induces prolonged arrest of human glioma cells in the G2/M phase of the cell cycle followed by a senescence-like phenomenon or mitotic catastrophe. These findings suggest that the G2 checkpoint is linked to DNA repair mechanisms. We investigated the effect of a cyclin-dependent kinase (Cdk) inhibitor flavopiridol (FP) that inhibits the action of Cdc2, a key protein in the G2 checkpoint pathway, on TMZ-treated glioma cells. Colony formation efficiency revealed that FP potentiated the cytotoxicity of TMZ in glioma cells in a p53-independent manner. This effect was clearly associated with the suppression of key proteins at the G2-M transition, accumulation of the cells exclusively at the G2 phase, and increase in a double-stranded DNA break marker (seen on performing immunoblotting). TMZ-resistant clones showed activation of the G2 checkpoint in response to TMZ, while FP treatment resensitized these clones to TMZ. FP also enhanced the cytotoxicity of TMZ in U87MG-AktER cells. Moreover, administration of TMZ and/or FP to nude mice with xenografted U87MG cells revealed that FP sensitized xenografted U87MG cells to TMZ in these mice. Our findings suggest that TMZ resistance could be promoted by enhanced DNA repair activity in the G2-M transition and that a Cdk inhibitor could suppress this activity, leading to potentiation of TMZ action on glioma cells. © 2013 Springer Science+Business Media New York.