Yuanli Zhao

Silent Intralesional Microhemorrhage as a Risk Factor for Brain Arteriovenous Malformation Rupture

Background and Purpose— We investigated whether brain arteriovenous malformation silent intralesional microhemorrhage, that is, asymptomatic bleeding in the nidal compartment, might serve as a marker for increased risk of symptomatic intracranial hemorrhage (ICH). We evaluated 2 markers to assess the occurrence of silent intralesional microhemorrhage: neuroradiological assessment of evidence of old hemorrhage—imaging evidence of bleeding before the outcome events–and hemosiderin positivity in hematoxylin and eosin-stained paraffin block sections. Methods— We identified cases from our brain arteriovenous malformation database with recorded neuroradiological data or available surgical paraffin blocks. Using 2 end points, index ICH or new ICH after diagnosis (censored at treatment, loss to follow-up, or death), we performed logistic or Cox regression to assess evidence of old hemorrhage and hemosiderin positivity adjusting for age, sex, deep-only venous drainage, maximal brain arteriovenous malformation size, deep location, and associated arterial aneurysms. Results— Evidence of old hemorrhage was present in 6.5% (n=975) of patients and highly predictive of index ICH (P<0.001; OR, 3.97; 95% CI, 2.1–7.5) adjusting for other risk factors. In a multivariable model (n=643), evidence of old hemorrhage was an independent predictor of new ICH (hazard ratio, 3.53; 95% CI, 1.35–9.23; P=0.010). Hemosiderin positivity was found in 36.2% (29.6% in unruptured; 47.8% in ruptured; P=0.04) and associated with index ICH in univariate (OR, 2.18; 95% CI, 1.03–4.61; P=0.042; n=127) and multivariable models (OR, 3.64; 95% CI, 1.11–12.00; P=0.034; n=79). Conclusions— The prevalence of silent intralesional microhemorrhage is high and there is evidence for an association with both index and subsequent ICH. Further development of means to detect silent intralesional microhemorrhage during brain arteriovenous malformation evaluation may present an opportunity to improve risk stratification, especially for unruptured brain arteriovenous malformations.

Morbidity after Hemorrhage in Children with Untreated Brain Arteriovenous Malformation

Background: Children with untreated brain arteriovenous malformations (bAVM) are at risk of encountering life-threatening hemorrhage very early in their lives. The primary aim of invasive treatment is to reduce unfavorable outcome associated with a bAVM rupture. A better understanding of the morbidity of bAVM hemorrhage might be helpful for weighing the risks of untreated bAVM and invasive treatment. Our aim was to assess the clinical outcome after bAVM rupture and identify features to predict severe hemorrhage in children. Methods: We identified all consecutive children admitted to our institution for bAVMs between July 2009 and December 2014. Clinical outcome after hemorrhagic presentation and subsequent hemorrhage was evaluated using the modified Rankin Scale (mRS) for children. The association of demographic characteristics and bAVM morphology with severe hemorrhage (mRS >3 or requiring emergency hematoma evacuation) was studied using univariate and multivariable regression analyses. A nomogram based on multivariable analysis was formulated to predict severe hemorrhage risk for individual patients. Results: A total of 134 patients were identified with a mean treatment-free follow-up period of 2.1 years. bAVM ruptured in 83 (62%) children: 82 had a hemorrhage at presentation and 6 of them experienced a recurrent hemorrhage during follow-up; 1 patient had other diagnostic symptoms but bled during follow-up. Among them, 49% (41/83) had a severe hemorrhage; emergency hematoma evacuation was required in 28% of them (23/83), and 24% (20/83) remained as disabled (mRS ≥3) at last follow-up. Forty-six percent (38/82) of children with hemorrhagic presentation were severely disabled (mRS >3). Forty-three percent (3/7) were severely disabled after subsequent hemorrhage. The annual rate of severe subsequent hemorrhage was 1% in the overall cohort and 3.3% in children with ruptured presentation. All the subsequent severe hemorrhage events occurred in children with severe hemorrhage history (7%, 3/41). Periventricular location, non-temporal lobe location, and long draining vein were predictors for severe hemorrhage in pediatric untreated bAVMs. A nomogram based on bAVM morphology was contracted to predict severe hemorrhage risk for individual patients, which was well calibrated and had a good discriminative ability (adjusted C-statistic, 0.72). Conclusions: Evaluating bAVM morbidity and morphology might be helpful for weighing the risks of untreated bAVM in pediatric patients.

Distinctive distribution of lymphocytes in unruptured and previously untreated brain arteriovenous malformation

Aim: To test the hypothesis that lymphocyte infiltration in brain arteriovenous malformation (bAVM) is not associated with iron deposition (indicator of micro-hemorrhage). Methods: Sections of unruptured, previously untreated bAVM specimens (n = 19) were stained immunohistochemically for T-lymphocytes (CD3 + ), B-lymphocytes (CD20 + ), plasma cells (CD138 + ) and macrophages (CD68 + ). Iron deposition was assessed by hematoxylin and eosin and Prussian blue stains. Superficial temporal arteries (STA) were used as control. Results: Both T-lymphocytes and macrophages were present in unruptured, previously untreated bAVM specimens, whereas few B cells and plasma cells were detected. Iron deposition was detected in 8 specimens (42%; 95% confidence intervals = 20-67%). The samples with iron deposition tended to have more macrophages than those without (666 ± 313 vs. 478 ± 174 cells/mm 2 ; P = 0.11). T-cells were clustered on the luminal side of the endothelial surface, on the vessel-wall, and in the perivascular regions. There was no correlation between T-lymphocyte load and iron deposition (P = 0.88). No macrophages and lymphocytes were detected in STA controls. Conclusion: T-lymphocytes were present in bAVM specimens. Unlike macrophages, the load and location of T-lymphocytes were not associated with iron deposition, suggesting the possibility of an independent cell-mediated immunological mechanism in bAVM pathogenesis.

Higher Flow Is Present in Unruptured Arteriovenous Malformations With Silent Intralesional Microhemorrhages

Background and Purpose— Silent microhemorrhage (hemosiderin) has been observed in resected brain arteriovenous malformations (bAVM) tissue and may represent a subgroup at increased risk for clinical hemorrhage. Previous studies suggest that ruptured bAVMs have faster flow and shorter mean transit time of contrast in blood vessels than unruptured bAVMs. We hypothesized that flow would be faster in unruptured AVMs with hemosiderin compared with those without hemosiderin. Methods— We selected unruptured, supratentorial bAVMs >3.5 cc with pathology specimens. Hemodynamic features were evaluated using color-coding angiography, including contrast mean transit time of AVM nidus, time to peak (TTP) of feeding artery (FA) and draining vein (DV), and the ratio (TTP DV/FA). Characteristics of 9 cases with hemosiderin and 16 without hemosiderin were compared using 2-sample t tests and Fisher exact tests. Results— No difference in FA TTP and DV TTP was observed between groups. However, cases with hemosiderin had significantly shorter mean transit time compared with those without hemosiderin (1.11±0.28 versus 1.64±0.55 seconds; P=0.013) and a lower ratio of DV TTP/FA TTP (1.48±0.32 versus 1.94±0.61; P=0.045). Presence of venous varix was significantly associated with hemosiderin (P=0.003). No other clinical or angioarchitectural factors were associated with hemosiderin. Conclusions— Shorter mean transit time through the AVM nidus, lower DV TTP/FA TTP, and the high prevalence of venous varices suggests that high flow is an important feature of unruptured bAVMs with hemosiderin.

Three-dimensional intracranial middle cerebral artery aneurysm models for aneurysm surgery and training.

To develop a realistic model of middle cerebral artery (MCA) aneurysms using three-dimensional (3D) printing for surgical planning, research, and training of neurosurgical residents. This study included eight MCA aneurysm cases. The aneurysm together with the adjacent arteries and skull base were printed based on raw computed tomography angiography (CTA) data using a 3D printer with acrylonitrile-butadiene-styrene as the model material. The aneurysm models were used for surgical planning, and craniotomy and clipping practice by neurosurgical residents. Feedback was obtained using a survey. 3D aneurysm models were created for all seven MCA aneurysm patients. There was good agreement in the model aneurysm diameter, width, and neck and the CTA data, with no significant difference (p > 0.05) among the groups. The simulator was useful for choosing the clips to use before surgery. The average response to each of the survey questions was greater than 3.85 (range 3.0-5.0) on a five-point scale. The 3D printed MCA aneurysm models were accurate. Simulation and practice using the 3D models was useful for understanding the aneurysm structure and choosing the clips to use before surgery, especially for junior neurosurgeons.

Multiple nodular dural cavernous angiomas occluding superior sagittal sinus and destructing calvarium: Case report and literature review

Dural cavernous angiomas (CAs) outside the middle cranial fossa are uncommon vascular lesions that generally present with benign clinical course compared to those within the middle cranial fossa. Aggressive invasion of these lesions is less common and mainly involves the skull. Dura sinus invasion and diffused nodular growth are exceedingly rare. We presented a case of a 33-year-old male with multiple nodular CAs growing in a sheet-like pattern along the falx cerebri and convexity dura, which occluded the superior sagittal sinus, destructed calvarium and were associated with an isolated skull CA on the right forehead. Both dura sinus and convexity skull were extensively invaded by these multiple dural CAs without obvious mass effect, suggesting an aggressive infiltration pattern. Invasive dural CAs have been predominantly observed in patients <40 year-old and might be along the extra-axial vasculature. Therefore, cavernous angiomas should be considered in the diagnosis of dura-based invasive lesions and a closer follow-up might be recommended for young patients with dural CAs adjacent to dura sinus or skull.

Cerebral ischemia at early postoperative period of direct revascularization for moyamoya disease: a case report and literature review

1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. 2China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. 3Department of Neurosurgery, Peking University International Hospital, Peking University Health Science Center, Beijing 102206, China. 4Center of Stroke, Beijing Institute for Brain Disorders, Beijing 100050, China. 5Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing 100050, China. *Authors contributed equally.