The role of the Sylvian fissure configuration and the vascular anatomy on different bleeding patterns in ruptured middle cerebral artery aneurysms.

OBJECTIVE: Ruptured middle cerebral artery (MCA) aneurysms are one of the causes of subarachnoid (SAH) or intracerebral hemorrhage (ICH) but the factors associated with the bleeding type are unknown. The aim of the study was to analyze the association of the morphological variations of the Sylvian fissure (SF) and vascular parameters on occurrence of different bleeding patterns in patients with ruptured MCA aneurysms. PATIENTS AND METHODS: The data of consecutive 202 patients with ruptured MCA aneurysm of two centers were included for analysis. Patients were divided into three groups: Group 1 with SAH, Group 2 with accompanying ICH and Group 3 with intrasylvian hemorrhage (ISH). The SF was divided into five types according to the previously described classification. Analyzed vascular parameters were aneurysm size, localization, presence of a daughter aneurysm, shape, and angulation of the aneurysm sac. RESULTS: A total of 202 patients (141 female, 61 male, mean age 52.4 yr) were included in this study. 67 patients (33.2%) had a SAH, 122 (60.4%) an ICH and 13 (6.4%) presented with ISH. Statistical analysis showed a significant association of narrow and twisted SF types 4 and 5 (p < 0.001) and temporal angulation of the aneurysm (p = 0.030) for occurrence of ICH. All other vascular parameters showed no significant association for any kind of hemorrhage. CONCLUSION: Our results allow the conclusion that the complex SF types 4 and 5, as well as the temporal angulation of the aneurysm sac are associated with the occurrence of ICH in ruptured MCA aneurysms.

Long-term outcomes of semi-implantable functional electrical stimulation for central drop foot.

BACKGROUND: Central drop foot is a common problem in patients with stroke or multiple sclerosis (MS). For decades, it has been treated with orthotic devices, keeping the ankle in a fixed position. It has been shown recently that semi-implantable functional electrical stimulation (siFES) of the peroneal nerve can lead to a greater gait velocity increase than orthotic devices immediately after being switched on. Little is known, however, about long-term outcomes over 12 months, and the relationship between quality of life (QoL) and gait speed using siFES has never been reported applying a validated tool. We provide here a report of short (3 months) and long-term (12 months) outcomes for gait speed and QoL. METHODS: Forty-five consecutive patients (91% chronic stroke, 9% MS) with central drop foot received siFES (Actigait®). A 10 m walking test was carried out on day 1 of stimulation (T1), in stimulation ON and OFF conditions, and repeated after 3 (T2) and 12 (T3) months. A 36-item Short Form questionnaire was applied at all three time points. RESULTS: We found a main effect of stimulation on both maximum (p < 0.001) and comfortable gait velocity (p < 0.001) and a main effect of time (p = 0.015) only on maximum gait velocity. There were no significant interactions. Mean maximum gait velocity across the three assessment time points was 0.13 m/s greater with stimulation ON than OFF, and mean comfortable gait velocity was 0.083 m/s faster with stimulation ON than OFF. The increase in maximum gait velocity over time was 0.096 m/s, with post hoc testing revealing a significant increase from T1 to T2 (p = 0.012), which was maintained but not significantly further increased at T3. QoL scores showed a main effect of time (p < 0.001), with post hoc testing revealing an increase from T1 to T2 (p < 0.001), which was maintained at T3 (p < 0.001). Finally, overall absolute QoL scores correlated with the absolute maximum and comfortable gait speeds at T2 and T3, and the increase in overall QoL scores correlated with the increase in comfortable gait velocity from T1 to T3. Pain was reduced at T2 (p < 0.001) and was independent of gait speed but correlated with overall QoL (p < 0.001). CONCLUSIONS: Peroneal siFES increased maximal and comfortable gait velocity and QoL, with the greatest increase in both over the first three months, which was maintained at one year, suggesting that 3 months is an adequate follow-up time. Pain after 3 months correlated with QoL and was independent of gait velocity, suggesting pain as an independent outcome measure in siFES for drop foot.

Intraventricular Hemorrhage Caused by Subarachnoid Hemorrhage: Does the Severity Matter?

OBJECTIVE: Aneurysm rupture might be accompanied by intraventricular hemorrhage (IVH), which is associated with poor outcome of subarachnoid hemorrhage (SAH). The aim of this study was to analyze risk factors and clinical impact of IVH severity. METHODS: A total of 995 consecutive patients with SAH treated at our institution between January 2003 and June 2016 were eligible for this study. Clinical and radiologic findings were correlated with the presence and severity of IVH assessed with the original Graeb score. RESULTS: A total of 487 patients with SAH (48.9%) presented with IVH (mean IVH severity, 5.48 points [±3.5]). IVH severity correlated with poorer initial clinical condition (World Federation of Neurosurgical Societies grade >3; P < 0.001), acute hydrocephalus (P = 0.001), and poor outcome at 6 months (modified Rankin Scale score >2; P < 0.001). The location of the ruptured aneurysm in the anterior cerebral artery independently predicted the occurrence (P = 0.007) and severity of IVH (P < 0.001). In turn, aneurysm size affected only the severity of IVH (P = 0.001) but not its occurrence (P = 0.153). Early complications of SAH occurring within 72 hours after the bleeding event (cerebral infarction [P = 0.043], early mortality [P = 0.001], and primary craniectomy [P = 0.043]) were independently associated with the severity of IVH. CONCLUSIONS: Severity of aneurysmal IVH is a strong contributor to initial severity and early complications of SAH. Patients with larger aneurysms, especially located in the anterior cerebral artery, are at particular risk of severe IVH in cases of aneurysm rupture.

Predictive anatomical factors for rupture in middle cerebral artery mirror bifurcation aneurysms.

OBJECTIVE The aim of this study was to define predictive factors for rupture of middle cerebral artery (MCA) mirror bifurcation aneurysms. METHODS The authors retrospectively analyzed the data in patients with ruptured MCA bifurcation aneurysms with simultaneous presence of an unruptured MCA bifurcation mirror aneurysm treated in two neurosurgical centers. The following parameters were measured and analyzed with the statistical software R: neck, dome, and width of both MCA aneurysms-including neck/dome and width/neck ratios, shape of the aneurysms (regular vs irregular), inflow angle of both MCA aneurysms, and the diameters of the bilateral A1 and M1 segments and the frontal and temporal M2 trunks, as well as the bilateral diameter of the internal carotid artery (ICA). RESULTS The authors analyzed the data of 44 patients (15 male and 29 female, mean age 50.1 years). Starting from the usual significance level of 0.05, the Sidak-corrected significance level is 0.0039. The diameter of the measured vessels was statistically not significant, nor was the inflow angle. The size of the dome was highly significant (p = 0.0000069). The size of the neck (p = 0.0047940) and the width of the aneurysms (p = 0.0056902) were slightly nonsignificant at the stated significance level of 0.0039. The shape of the aneurysms was bilaterally identical in 22 cases (50%). In cases of asymmetrical presentation of the aneurysm shape, 19 (86.4%) ruptured aneurysms were irregular and 3 (13.6%) had a regular shape (p = 0.001). CONCLUSIONS In this study the authors show that the extraaneurysmal flow dynamics in mirror aneurysms are nonsignificant, and the aneurysmal geometry also does not seem to play a role as a predictor for rupture. The only predictors for rupture were size and shape of the aneurysms. It seems as though under the same conditions, one of the two aneurysms suffers changes in its wall and starts growing in a more or less stochastic manner. Newer imaging methods should enable practitioners to see which aneurysm has an unstable wall, to predict the rupture risk. At the moment one can only conclude that in cases of MCA mirror aneurysms the larger one, with or without shape irregularities, is the unstable aneurysm and that this is the one that needs to be treated.

TNF alpha signaling is associated with therapeutic responsiveness to vascular disrupting agents in endocrine tumors.

ASA404 (Vadimezan) belongs to a class of agents with disrupting properties against tumor vasculature, which is partly mediated by TNFα-signaling. Preclinical and early clinical studies have indicated promising results for ASA404, while extended clinical trials performed poorly. Our aim was to investigate the potential therapeutic applicability of ASA404 against endocrine tumors. Moreover, as the reason for the unpredictable clinical anti-tumor activity of ASA 404 remained uncertain in previous studies, we compared two tumor models of endocrine origin with different responses to ASA404 treatment. Specifically, we determined anti-tumoral effects in preclinical models of neuroendocrine tumors of the gastroenteropancreatic system (BON) and adrenocortical cancer (NCI-H295R) in vitro and in xenograft models in vivo. Upon treatment of tumor bearing mice significant anti-tumoral effects, an increase in TNFα as well as activation of TNFα-specific downstream signaling were evident in the BON tumor model while no comparable effects were detectable for NCI-H295R. We identified TNFAIP3/A20, a key molecule of an inhibitory feedback-loop downstream of TNF-receptor 1, CD40, Toll-like receptors, NOD-like receptors and the interleukin-1 receptor signaling cascades, as overexpressed in the adrenocortical carcinoma tumor model. Subsequent analyses of clinical patient samples confirmed a correlation between tumor TNFAIP3 expression levels and overall survival in patients with ACC. Taken together our findings provide evidence that modulation of TNFα-signaling could be of relevance both for the clinical course of ACC patients and as a marker of treatment response.