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This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.

Purpose: Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm 3 ) or brain metastases located next to critical structures., Material and Methods: Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated., Results: Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity., Conclusion: The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Cavernous malformations (CM) represent a distinct subgroup of brain vascular malformations that are characterized by small sinusoidal vascular channels with hyaline degeneration and old blood pigments. Because of the increasing availability of magnetic resonance imaging (MRI) they are detected much more frequently in the present era. CM may be solitary or found in the context of a familial variant that results in an increasing number of CM developing as the patient ages. Because of the variable risk of subacute bleeding, their management options have been controversial. The annual risk of an incidentally detected CM bleeding is <0.5% each year. Leksell radiosurgery is used for a subgroup of patients who have repeatedly bled. In general, CM best considered for stereotactic radiosurgery are deep seated and do not pre-sent to a pial or ependymal surface where microsurgical corridors for removal are feasible. When radiosurgery is used for patients at high risk for both re-bleeding as well as microsurgical resection, the risk of bleeding can be reduced from as high as 33% each year to <0.5% each year after a 2-year latency interval. The target lies within the hemosiderin rim detected during the MRI that is part of planning. Marginal doses are significantly less than those used for angiographically visible arteriovenous malformations., (© 2019 S. Karger AG, Basel.)

Background: Current surgical therapies for spontaneous intracerebellar hemorrhage (SCH) include suboccipital craniotomy (SC), stereotactic aspiration and thrombolysis (SAT), and endoscopic surgery (ES). Evidence comparing the therapeutic effects of these 3 methods is scarce. The safety and efficacy of SC, SAT, and ES for SCH are still uncertain., Methods: 75 patients with SCH who received SC, SAT, or ES were reviewed retrospectively. Baseline parameters before the operation, evacuation rate, perihematoma edema, postoperative complications, and cumulative case fatalities were collected. Also, 12 months after ictus, the long-term functional outcomes in patients with regard to fourth ventricle compression and age were judged, respectively, by the modified Rankin Scale (mRS)., Results: The SAT was less effective in evacuating hematoma than were SC and ES. The perihematoma edema on postoperative day 7 and surgical complications were highest in the SC group. The functional outcome represented by mRS was better in the SAT group than in the SC and ES groups for patients with fourth ventricle compression grade 1. For patients with fourth ventricle compression grades 2 and 3, the ES group achieved the best functional outcome. Patients older than 60 years benefited less from SC than from ES and SAT., Conclusions: SAT may be suitable for SCH patients with fourth ventricle compression grade 1, and ES may be suitable for SCH patients with fourth ventricle compression grades 2 and 3. Aged patients benefit less from SC than from SAT and ES., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To evaluate the clinical value of minimally invasive stereotactic puncture therapy (MISPT) combined with external ventricular drainage (EVD) on secondary intraventricular hemorrhage (SIVH)., Methods: A retrospective analysis of the patients of intraventricular hemorrhage from May 2013 to January 2015 was conducted in our hospital, according to the enrollment criterion; of which 40 patients were treated by MISPT combined with EVD (ME group) and 45 patients by conventional craniotomy combined with EVD (CE group). Related indicators were compared in the two groups of patients with short- and long-term efficacy., Results: The patients in the ME group showed obvious amelioration in the GCS score compared with that of the CE group. There were no statistically significant differences in Graeb score and hematoma volume. Compared with the CE group, the incidence of postoperative complications was significantly decreased in the ME group. The mortalities of the ME and CE groups were 13.3% and 22.6%, respectively. The incidences of rebleeding in the ME and CE groups were 10.0% and 15.6%, respectively. For the four parameters representing long-term efficacy of 6 months postoperation, the Glasgow Outcome Scale (GOS), Barthel Index (BI), modified Rankin Scale (mRS), and Karnofsky Scale (KPS) scores in the ME group were ameliorated more significantly than those of the CE group., Conclusions: Our data showed that the main advantages of ME in the treatment for SIVH were in minimal trauma, low incidence of complications, and the possibility to improve the long-term prognosis significantly.

OBJECTIVE Ruptured arteriovenous malformations (AVMs) are often obliterated after emergency microsurgical treatment. However, some studies have reported AVM recurrence after the obliteration of ruptured AVMs. The authors report their experience with AVM recurrence after successful microsurgical treatment of ruptured AVMs. METHODS The authors reviewed the medical data of 139 consecutive patients who underwent microsurgery at the authors' institution for ruptured AVM between 2002 and 2012. Each patient underwent a conventional cerebral angiography examination immediately after the surgery. Subsequent follow-ups were performed with MR angiography after 6 months, and, if there was no indication of AVM recurrence, patients were followed up with conventional cerebral angiography between 1 and 2 years after the treatment; pediatric patients were followed up until age 18 years. Recurrence was defined as new radiological evidence of an AVM at the site of a ruptured AVM or a new hemorrhage in patients with angiographically documented AVM obliteration on postoperative angiograms. RESULTS The mean age of the patients at the time of ruptured AVM diagnosis was 30.8 years (SD ± 5, range 4-69 years), and 44 of the patients were younger than 18 years (the mean age at diagnosis in this pediatric subgroup was 11.4 years [range 4-17.9 years]). Complete AVM obliteration after the initial microsurgery was observed in 123 patients (89.5%). Reappearance of an AVM was noted in 7 patients between 12 and 42 months after the treatment, and all of these patients were younger than 18 years. The recurrent AVM was located in an eloquent zone in 4 patients, and deep venous drainage was noted in 3 patients. Radiosurgery was performed in 6 of these patients, and 1 patient underwent another microsurgical procedure. The authors noted only one rebleeding due to an AVM recurrence during the latency period after radiosurgery. CONCLUSIONS The recurrence of an AVM is fairly rare and affects mostly pediatric patients. Therefore, especially in children, long-term angiographic follow-up is required to detect AVM recurrence or an AVM remnant. The authors stress the need for discussion involving a multidisciplinary neurosurgical team to decide on treatment in cases of any AVM recurrence or remnant.

OBJECTIVE Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes. METHODS The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses. RESULTS The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm 3 , 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis. CONCLUSIONS Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.

Background: The angioarchitecture of arteriovenous fistulas (AVFs) of cerebral arteriovenous malformation (CAVM) after stereotactic radiosurgery (SRS) remain unclear. The purpose of this study is to report the angiographic change of AVF components of CAVMs after SRS and outcomes of endovascular embolisation., Methods: From 2002 to 2012, a total of 523 CAVMs had been treated primarily by SRS with more than 3-year latency. Among these databases, there were 19 patients with 21 AVFs undergoing embolization after SRS. We retrospectively analyzed the angioarchitecture of the CAVM to identify AVFs, morphologic change and outcomes of AVFs after SRS and embolisation., Results: Eight AVFs were in the periphery of CAVMs, the other 13 were in a central location. Eighteen of 21 AVFs remained constant in morphology after SRS, while three feeders of AVFs were associated with radiation arteritis. The causes of failure to identify AVFs before SRS were overlooked (n = 7) or there was superimposition with feeders, nidus and/or venous drains of CAVMs (n = 14). Total fistula occlusion was achieved in all 21 AVFs; residual CAVMs was totally obliterated by embolisation and/or additional SRS in 12 patients. One patient had a small procedure-related intracerebral hemorrhage. Mean follow-up period was 26 months., Conclusions: Early detection of AVF components of CAVMs prior to SRS may be difficult, particularly those in a central location. However, most AVFs became evident and showed consistency in angiographic morphology after obliteration of the majority nidus parts of CAVMs. Endovascular embolisation is effective in managing these AVF components.

We describe a case of a 78-year-old man who, on two occasions, had intracerebral hemorrhage with an atypical, predominantly psychiatric presentation: once with major depression without focal neurological signs and the second time with severe behavioral disturbance and only mild facial paralysis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To analyse the imaging and clinical prognostic indicators for early hematoma enlargement after spontaneous intracerebral hemorrhage (ICH)., Methods: In 126 patients, spontaneous ICH was diagnosed by computed tomography (CT) within 4 hours of disease onset. Repeat CT was performed after 24 hours to detect the development of hematoma enlargement. A regression equation was obtained by first examining the significance of correlations between possible risk factors and early hematoma progression, followed by verification using multivariate stepwise regression., Results: The incidence of early hematoma enlargement after spontaneous ICH was 25.4%, and the significant prognostic indicators were CT hematoma inhomogeneity, degree of consciousness impairment on admission and time between disease onset and initial CT. In addition, the characteristic 'hematoma enlargement border' on CT has important prognostic value in early hematoma enlargement., Conclusion: Clear prognostic indicators exist for early hematoma enlargement after spontaneous ICH, suggesting that hematoma inhomogeneity has important implications for predicting ICH progression, and we discovered as well as defined the 'hematoma enlargement border', an imaging characteristic of early hematoma enlargement.

Non-aneurismatic spontaneous cerebral hemorrhage or intracranial hemorrhage accounts for 10-15% of total cerebral vascular accidents. Depending on its site it can may be intraparenchymal or intraventricular. The most frequent location is in the basal ganglia and its predominant etiology is poorly-controlled arterial hypertension. In Spain, the incidence of intracerebral hemorrhage is estimated to be 15 cases per 100,000 population/ year, this being more frequent in males over 55 years old. Intracranial hemorrhage is less frequent than ischemic stroke, but has higher mortality and morbidity, it being one of the first causes of severe disability. Cerebral hemorrhage is not a monophasic phenomenon which abates immediately, because the hematoma continues to increase in the first 24 hours. Due to this reason and because of their characteristics of the disease itself, these are critical patients who must be admitted in to Intensive Care Unit where hemodynamic and cardiorespiratory control should be made as well as strict monitoring of the awareness level and remaining neuromonitoring standard parameters. In this paper, we review some aspects of the epidemiology, physiopathology, clinical presentation, diagnosis and the different therapeutic options, performing an up-date on the treatment of intracranial hemorrhage from both the medical and surgical point of view.

Inducible heat shock protein 70 (HSP70), a stress protein detected in the central nervous system, is expressed when a cell or organism is under stress. Interleukin-18 (IL-18) and tumor necrosis factor alpha (TNF-alpha) are multipotential early proinflammatory cytokines. Our objective was to determine protein levels of HSP70, IL-18, and TNF-alpha as well as mRNA levels of HSP70, IL-18, and TNF-alpha in the plasma and CSF of spontaneous intracerebral hemorrhage (ICH) patients, and to correlate these with disease outcome. Serial measurement of the proteins in CSF and plasma and of the mRNAs in peripheral blood mononuclear cells was conducted in 43 patients (mean age, 64+/-9 years; 23 men and 20 women). Ten (23%) patients died. We found that the damaged brain releases TNF-alpha and HSP70 to the peripheral blood and that plasma levels of these are highly associated with mortality in spontaneous ICH patients.

Rationale and Objectives: To evaluate the clinical utility of cranial computed tomography (CT) in pediatric and adult patients during ongoing extracorporeal membrane oxygenation (ECMO) treatment from acute respiratory failure and to assess the frequency of intracranial hemorrhage (ICH) and infarction during the treatment., Materials and Methods: The medical records of 123 consecutive patients, 54 children (ages 3 months-17 years) and 69 adults (ages 18-62 years), treated with ECMO over a 10-year period were searched for cranial CT performed during ECMO. Indications for CT, CT findings, impact on clinical management, and patient outcome were noted. In addition, all CT scans were reviewed for the frequency of ICH or infarction., Results: Seventy-eight patients had cranial CT while on ECMO. ICH or cerebral infarction were detected in 45 (37%) of the 123 patients. Eighteen patients (15%) had focal hemorrhage, 11 (9%) focal infarction, and 16 (13%) general brain edema. In 16 of the 45 patients, the CT findings were decisive to withdraw the ECMO treatment. Five patients were weaned from ECMO, and in four patients the findings motivated cranial surgery during ECMO. In the remaining 20 patients with less extended intracranial pathology, the ECMO treatment was continued with high survival., Conclusion: Cranial CT has an important role during ECMO treatment to reveal or exclude severe intracranial complications where ECMO treatment should be discontinued. Less severe complications have a favorable prognosis with continued treatment. Our study suggests an underreporting of intracranial complications in adults and pediatric patients on ECMO because of low utilization of neuroimaging.

Introduction: Intracerebral hemorrhage (ICH) associated with pregnancy commonly occurs in the postpartum period in the setting of preeclampsia/eclampsia. We describe the clinical course of two patients with ICH due to postpartum cerebral vasculopathy in the absence of toxemia., Methods: We reviewed two cases with ICH and postpartum vasculopathy in our hospital (1996-2001) and compared them with seven similar case reports from the literature., Results: Mean age of all patients is 28.7+/-5.6 years (mean+/-S.D.). Toxemia of pregnancy was absent in all cases. ICHs were cortical in eight and putaminal in one patient. Erythrocyte sedimentation rate was elevated in two. Two cases rehemorrhaged during the same admission. No cerebral infarctions were reported. All patients had diffuse vasculopathy on conventional catheter angiography, with no clinical manifestations or laboratory data supportive of extracerebral or systemic vasculitis. Eight patients were treated with corticosteroids, two with additional cytotoxic agents and one with nimodipine alone. Improvement on follow-up cerebral angiography (catheter or MRA) and transcranial Doppler ultrasonography (TCD) was noted in eight cases. One did not have follow-up cerebral imaging but had an excellent clinical outcome. All cases had good to excellent functional recovery., Conclusions: Postpartum ICH in the absence of toxemia may be associated with isolated cerebral vasculopathy. The clinical course and functional outcome is good to excellent. This entity appears to be distinct from cerebral vasculitis, which is usually associated with poor outcome.

A 50-year-old male presented with a central neurocytoma with intratumoral homorrhage. He had undergone partial removal of the tumor and postoperative radiation therapy 15 years previously. He was followed as an outpatient after the initial treatment, and there was no evidence of regrowth of the residual tumor. Removal of the hematoma and biopsy of the tumor were performed. Abnormally developed blood capillaries in the tumor may have undergone disturbances of circulation caused by irradiation which resulted in bleeding. Patients with partially resected central neurocytomas which have low proliferative potential may not require radiation therapy, due to the benign nature and the risk of delayed complications of irradiation including intratumoral hemorrhage.

Congenital arteriovenous malformation (AVM) of the brain represents a defect in capillary development resulting in a high flow fistula between arterial and venous systems. In this study, AVM hemodynamics were related with clinical findings. Volume flow was calculated based on transcranial Doppler (TCD) and angiographic data. Forty patients admitted to the Massachusetts General Hospital for proton beam therapy (33 +/- 10 yr old; mean +/- SD) were studied. Four symptoms were considered: intracranial bleeding, progressive neurological deficit, seizures, and headache. Fourteen control subjects aged 30 +/- 7 years (mean +/- SD) were normal volunteers. Angiography with calibrated markers permitting magnification correction was available for all patients. Lateral and medial depth limits of the intracranial basal arteries in relation to the TCD temporal window were determined by TCD and angiogram with excellent correlation. Selected depth for data acquisition was determined independently in the angiogram and by TCD. The difference between the two techniques was less than 4 mm. Mean flow velocity, pulsatility index, and vessel diameter were studied. Flow volume was calculated from these data. Mean flow velocity, pulsatility index, vessel diameter, and flow volume were significantly different among AVM feeders, non-feeders, and control arteries. The non-feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 254 +/- 13, 136 +/- 14, and 79 +/- 8 ml/min, respectively. Accordingly, the estimated cerebral flow volume was 938 ml/min. The feeding middle cerebral artery, anterior cerebral artery, and posterior cerebral artery flows were 552 +/- 47, 369 +/- 70, and 484 +/- 67 ml/min, respectively (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A case of an 18-year-old female, who developed an intraventricular hemorrhage and recurrent cerebral ischemic r attacks with Moyamoya like angiographical findings was reported. Lupus Anticoagulant (LA) was present in the patient's plasma. Cerebral angiography demonstrated stenosis and occlusion of the intracranial major arteries. Hemorrhagic episodes in patient's with LA is quite rare. The mechanism of intraventricular hemorrhage and the significance of LA in the differential diagnosis of Moyamoya disease are discussed.

Twenty-six patients with arteriovenous malformations (AVMs) were treated between 1965 and 1986 with conventional fractionated radiotherapy at the Royal Marsden Hospital. There were 14 male patients and 12 female, aged 11 to 57 years (median, 24 yr). Twenty-five patients completed radiotherapy with a localized treatment target volume of a dose of 40 to 54 Gy. The median follow-up was 14.5 years. Eleven patients had an additional hemorrhage. The actuarial annual risk of bleeding was 2.3%, which is similar to that found in untreated patients. Follow-up angiograms were performed in 11 patients, and 10 showed persistence of AVM. The results suggest that fractionated radiotherapy in conventional doses does not make a large impact on the risk of hemorrhage in patients with inoperable AVMs, and, where possible, stereotactic external beam radiotherapy/radiosurgery should be employed.

Forty patients aged 6 to 18 years have now been treated for inoperable intracranial arteriovenous malformations (AVMs) using stereotactic heavy-charged-particle Bragg peak radiosurgery at the Lawrence Berkeley Laboratory 184-inch Synchrocyclotron at the University of California, Berkeley. This paper describes the procedures for selection of patients, the treatment protocol, and the neurological and neuroradiological responses to stereotactic radiosurgery in this age group. The volumes of the treated AVMs ranged from 265 mm3 to 60,000 mm3. The results are favorable: thus far, 20 of 25 patients have experienced greater than or equal to 50% obliteration of their AVMs within 1 year after treatment, and 14 of 18 patients have experienced total obliteration of the AVM by 2 years after treatment. Two patients hemorrhaged from radiosurgically treated AVMs within 12 months after treatment, but none thereafter. Complications include vasogenic edema and arterial occlusion; three patients have had neurological worsening as definite or possible sequelae of treatment. The strengths and limitations of the method are discussed.