Eric S. Sussman, Venkatesh Madhugiri, Mario Teo, Troels H. Nielsen, Sunil V. Furtado, Arjun V. Pendharkar, Allen L. Ho, Rogelio Esparza, Tej D. Azad, Michael Zhang and Gary K. Steinberg
Revascularization surgery is a safe and effective surgical treatment for symptomatic moyamoya disease (MMD) and has been shown to reduce the frequency of future ischemic events and improve quality of life in affected patients. The authors sought to investigate the occurrence of acute perioperative occlusion of the contralateral internal carotid artery (ICA) with contralateral stroke following revascularization surgery, a rare complication that has not been previously reported.
This study is a retrospective review of a prospective database of a single surgeon’s series of revascularization operations in patients with MMD. From 1991 to 2016, 1446 bypasses were performed in 905 patients, 89.6% of which involved direct anastomosis of the superficial temporal artery (STA) to a distal branch of the middle cerebral artery (MCA). Demographic, surgical, and radiographic data were collected prospectively in all treated patients.
Symptomatic contralateral hemispheric infarcts occurred during the postoperative period in 34 cases (2.4%). Digital subtraction angiography (DSA) was performed in each of these patients. In 8 cases (0.6%), DSA during the immediate postoperative period revealed associated new occlusion of the contralateral ICA. In each of these cases, revascularization surgery involved direct anastomosis of the STA to an M4 branch of the MCA. Preoperative DSA revealed moderate (n = 1) or severe (n = 3) stenosis or occlusion (n = 4) of the ipsilateral ICA and mild (n = 2), moderate (n = 4), or severe (n = 2) stenosis of the contralateral ICA. The baseline Suzuki stage was 4 (n = 7) or 5 (n = 1). The collateral supply originated exclusively from the intracranial circulation in 4/8 patients (50%), and from both the intracranial and extracranial circulation in the remaining 50% of patients. Seven (88%) of 8 patients improved symptomatically during the acute postoperative period with induced hypertension. The modified Rankin Scale (mRS) score at discharge was worse than baseline in 7/8 patients (88%), whereas 1 patient had only minor deficits that did not affect the mRS score. At the 3-year follow-up, 3/8 patients (38%) were at their baseline mRS score or better, 1 patient had significant disability compared with preoperatively, 2 patients had died, and 1 patient was lost to follow-up. Three-year follow-up is not yet available in 1 patient.
Acute occlusion of the ICA on the contralateral side from an STA-MCA bypass is a rare, but potentially serious, complication of revascularization surgery for MMD. It highlights the importance of the hemodynamic interrelationships that exist between the two hemispheres, a concept that has been previously underappreciated. Induced hypertension during the acute period may provide adequate cerebral blood flow via developing collateral vessels, and good outcomes may be achieved with aggressive supportive management and expedited contralateral revascularization.
Michael Zhang, Yi-Ren Chen, Steven D. Chang and Anand Veeravagu
Symptomatic vertebral hemangiomas (SVHs) are a very rare pathology that can present with persistent pain or neurological deficits that warrant surgical intervention. Given the relative rarity and difficulty in assessment, the authors sought to present a dedicated series of SVHs treated using stereotactic radiosurgery (SRS) to provide insight into clinical decision making.
A retrospective review of a single institution's experience with hypofractionated radiosurgery for SVH from 2004 to 2011 was conducted to determine the clinical and radiographic outcomes following SRS treatment. The authors report and analyze the treatment course of 5 patients with 7 lesions, 2 of which were treated primarily by SRS.
Of the 5 patients studied, 4 presented with a chief complaint of pain refractory to conservative measures. Three patients reported dysesthesias, and 2 reported upper-extremity weakness. Following radiosurgery, 4 of 5 patients exhibited improvement in their primary symptoms (3 for pain and 1 for weakness), achieving a clinical response after a mean period of 1 year. In 2 cases there was 20%–40% reduction in lesion size in the most responsive dimension as noted on images. All treatments were well tolerated.
SRS for SVH is a safe and feasible treatment strategy, comparable to prior radiotherapy studies, and in select cases may successfully confer delayed decompressive effects. Additional investigation will determine future patient selection and how conformal SRS treatment can best be administered.
Hangjun Ruan, Lily Hu, Jingli Wang, Tomoko Ozawa, Nader Sanai, Michael Zhang, Kathleen R. Lamborn and Dennis F. Deen
The presence of hypoxic cells in human brain tumors contributes to the resistance of these tumors to radiation therapy. However, because normal tissues are not hypoxic, the presence of hypoxic cells also provides the potential for designing cancer-specific gene therapy. Suicide genes can be expressed specifically in hypoxic conditions by hypoxia-responsive elements (HREs), which are activated through the transcriptional complex hypoxia-inducible factor–1 (HIF-1).
The authors have transfected the murine BAX–green fluorescent protein (GFP) fusion gene under the regulation of three copies of HRE into U-87 MG and U-251 MG cells and selected stably transfected clones. Even though BAX was expressed under both oxic and anoxic conditions in these clones, cell survival assays demonstrated increased cell killing under anoxic as compared with oxic conditions. Cells obtained from most of these clones did not grow in vivo, or the tumors exhibited highly variable growth rates. However, cells obtained from the U-251 MG clone A produced tumors that grew as well as tumors derived from parental cells, and examination of the tumor sections under fluorescent microscopy revealed GFP expression in localized regions. Western blot analyses confirmed an increased BAX expression in these tumors. Analysis of the results suggests that HRE-regulated BAX can be a promising tool to target hypoxic brain tumor cells. However, there are measurable levels of BAX-GFP expression in this three-copy HRE–mediated expression system under oxia, suggesting promoter leakage. In addition, most clones did not show significant induction of BAX-GFP under anoxia. Therefore, the parameters of this HRE-mediated expression system, including HRE copy number and the basal promoter, need to be optimized to produce preferential and predictable gene expression in hypoxic cells.