Stanford Moyamoya Publications

Moyamoya Disease and Pediatrics

Zhao, M. Y., Alexander, S., Lopez, C. A., Zhang, H., Morton, G., Armindo, R. D., Yeom, K. W., Tong, E., Soares, B. P., Lee, S., Moseley, M. and Steinberg, G. K. (2025). "Characterizing pre- and post-operative cerebral blood flow and transit time in pediatric moyamoya patients using multi-delay ASL and DSC MRI." J Cereb Blood Flow Metab: 271678X251358979.

Cerebral blood flow (CBF) and blood movement are key to brain health. This study examined 22 children with moyamoya disease using a method called multi-delay arterial spin labeling (ASL) alongside DSC MRI to assess changes before and after surgeries to improve blood flow. Results showed that after surgery, blood flow increased significantly (24% with ASL, 7.6% with DSC), and blood movement improved (12% with ASL, 15% with DSC). The close correlation between the two methods indicates that multi-delay ASL is effective for measuring blood flow in children.

Sun, L. R., Vossough, A., Kossorotoff, M., Bang, O. Y., Smith, E., Phi, J. H., Dlamini, N., Steinberg, G. K., Lehman, L. L. and Lee, S. (2025). "Moyamoya Across the Lifespan: Current Neurologic Care and Future Directions." Neurology 104(7): e213484.

Moyamoya arteriopathy is a major cause of stroke, particularly in East Asia. The R4810K variant of the RNF213 gene is linked to severe, early-onset vasculopathy. Diagnosis relies on neuroimaging, while medical management focuses on reducing stroke risks and addressing conditions like headaches and epilepsy, often using antiplatelet therapy despite limited evidence. Surgical revascularization improves blood flow but has a 4%-18% risk of perioperative ischemic events. Long-term care includes neuroimaging and management of neuropsychological effects. This review discusses moyamoya evaluation and management across age groups and ongoing research to enhance patient care.

Zhao, M. Y., Tong, E., Duarte Armindo, R., Fettahoglu, A., Choi, J., Bagley, J., Yeom, K. W., Moseley, M., Steinberg, G. K. and Zaharchuk, G. (2024). "Short- and Long-Term MRI Assessed Hemodynamic Changes in Pediatric Moyamoya Patients After Revascularization." J Magn Reson Imaging 59(4): 1349-1357.

This study examined 46 pediatric patients (ages 11 months to 18 years) with Moyamoya disease to assess changes in blood flow and cerebrovascular reserve (CVR) before and after bypass surgeries using a non-invasive MRI technique called arterial spin labeling (ASL). Imaging was done two weeks before, and one week and six months after surgery.

Results showed blood flow increased by 41% within a week and 51% after six months, CVR improved by 68%, and arterial transit time decreased by 6.6%. These findings indicate that bypass surgery can enhance blood flow and CVR in children with Moyamoya disease both in the short and long term.

Sun, L. R., Jordan, L. C., Smith, E. R., Aldana, P. R., Kirschen, M. P., Guilliams, K., Gupta, N., Steinberg, G. K., Fox, C., Harrar, D. B., Lee, S., Chung, M. G., Dirks, P., Dlamini, N., Maher, C. O., Lehman, L. L., Hong, S. J., Strahle, J. M., Pineda, J. A., Beslow, L. A., Rasmussen, L., Mailo, J., Piatt, J., Lang, S. S., Adelson, P. D., Dewan, M. C., Mineyko, A., McClugage, S., Vadivelu, S., Dowling, M. M. and Hersh, D. S. (2024). "Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study." Neurocrit Care 40(2): 587-602.

Surgical revascularization lowers long-term stroke risk in children with moyamoya arteriopathy but may increase perioperative stroke risk. To address the lack of evidence-based guidelines, a modified Delphi process was conducted with 30 North American experts to establish consensus on perioperative care for indirect revascularization surgery. Consensus was reached on 39 key practices, including preadmission for high-risk children, administration of intravenous isotonic fluids, continuation of aspirin, and specific monitoring protocols post-surgery. The process also identified research priorities, such as the role of continuous electroencephalography, optimal blood pressure and hemoglobin targets, and the use of supplemental oxygen for suspected postoperative ischemia.

Yedavalli, V. S., Quon, J. L., Tong, E., van Staalduinen, E. K., Mouches, P., Kim, L. H., Steinberg, G. K., Grant, G. A., Yeom, K. W. and Forkert, N. D. (2022). "Intracranial Artery Morphology in Pediatric Moya Moya Disease and Moya Moya Syndrome." Neurosurgery 91(5): 710-716.

Moya Moya disease (MMD) and Moya Moya syndrome (MMS) are cerebrovascular disorders in children affecting the internal carotid arteries. This study quantitatively assessed arterial differences in 17 pediatric MMD/MMS patients (mean age 10.0 years) compared to 98 children with normal vessel morphology (mean age 10.6 years) using MR angiography (MRA). Researchers found significantly smaller radii in the internal carotid artery (ICA), middle cerebral artery (MCA-M1, MCA-M2), and anterior cerebral artery (ACA) in the MMD/MMS group (P < .001), while no significant differences were noted for the posterior cerebral artery (PCA) or basilar artery (BA). The study highlights the potential of automated methods for characterizing the cerebrovascular system in pediatric MMD/MMS management.

Salimi-Jazi, F., Wood, L. S. Y., Jones, R. E., Chandler, J., Rafeeqi, T., Dutta, S., Steinberg, G. and Bruzoni, M. (2022). "Ten-year experience with laparoscopic pedicled omental flap for cerebral revascularization in patients with Moyamoya disease." J Pediatr Surg 57(11): 710-715.

The omental flap is useful for reconstruction and revascularization in Moyamoya disease patients. This study reviews a 10-year experience with laparoscopic harvesting of the omental flap in 21 patients from 2011 to 2021. Three intraoperative complications were noted, with an average length of stay of 6 days, including 3 days in the ICU. Post-discharge complications included an epigastric incisional hernia and partial scalp necrosis, while one patient needed a direct bypass due to disease progression. The findings suggest that laparoscopic pedicled omental flap mobilization is a safe and effective method for indirect cerebral revascularization in these patients.

Rao, V. L., Prolo, L. M., Santoro, J. D., Zhang, M., Quon, J. L., Jin, M., Iyer, A., Yedavalli, V., Lober, R. M., Steinberg, G. K., Yeom, K. W. and Grant, G. A. (2022). "Acetazolamide-Challenged Arterial Spin Labeling Detects Augmented Cerebrovascular Reserve After Surgery for Moyamoya." Stroke 53(4): 1354-1362.

Cerebrovascular reserve (CVR) is linked to stroke risk in children with Moyamoya disease and can improve with revascularization surgery. This study assessed whether acetazolamide-challenged arterial spin labeling (ASL) could quantify CVR increases post-surgery and correlate with angiographic scoring. Analyzing 32 pediatric patients who underwent revascularization from 2012 to 2019, results showed a significant increase in median CVR in the ipsilateral middle cerebral artery territory after surgery (6.9 to 16.5 mL/100 g per minute, P<0.01), with no significant changes in other territories. Patients with Matsushima grade A perfusion had higher CVR than those with grades B or C (25.8 vs. 17.5 mL, P=0.02). The type of bypass did not significantly affect CVR increases. The study concludes that acetazolamide-challenged ASL effectively quantifies CVR enhancement after Moyamoya surgery.

Quon, J. L., Kim, L. H., MacEachern, S. J., Maleki, M., Steinberg, G. K., Madhugiri, V., Edwards, M. S. B., Grant, G. A., Yeom, K. W. and Forkert, N. D. (2020). "Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease." Neurosurgery 86(4): 530-537.

This study examined brain diffusion changes in 29 children with moyamoya disease, who had normal pre-surgery MRIs, compared to 60 healthy peers. Results indicated significantly higher diffusion values in several brain areas of the children with moyamoya, despite no size differences. These findings suggest that even without visible stroke signs, children with moyamoya may experience altered brain water movement, indicating potential underlying blood flow issues.

Quon, J. L., Kim, L. H., MacEachern, S. J., Maleki, M., Steinberg, G. K., Madhugiri, V., Edwards, M. S. B., Grant, G. A., Yeom, K. W. and Forkert, N. D. (2020). "In Reply: Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease." Neurosurgery 87(3): E436-E437.

Quon, J. L., Kim, L. H., Lober, R. M., Maleki, M., Steinberg, G. K. and Yeom, K. W. (2019). "Arterial spin-labeling cerebral perfusion changes after revascularization surgery in pediatric moyamoya disease and syndrome." J Neurosurg Pediatr 23(4): 486-492.

Moyamoya disease requires careful monitoring, and this study investigated the use of arterial spin labeling (ASL), a non-invasive MRI technique, in pediatric patients after revascularization surgery. Researchers analyzed 15 children and found that blood flow significantly increased in the middle cerebral artery territory post-surgery, indicating improved perfusion. However, blood flow to the basal ganglia decreased, suggesting changes in collateral blood supply. Overall, ASL effectively assessed blood flow changes in children after moyamoya surgery and may enhance routine patient monitoring.

Gupta, M., Choudhri, O. A., Feroze, A. H., Do, H. M., Grant, G. A. and Steinberg, G. K. (2016). "Management of moyamoya syndrome in patients with Noonan syndrome." J Clin Neurosci 28: 107-111.

This report highlights four cases of patients with Noonan syndrome who developed moyamoya syndrome, leading to headaches and strokes affecting one side of their bodies. Each patient underwent successful surgery to improve blood flow: a 10-year-old girl recovered well after a stroke, an adult with a childhood stroke improved but still had mini-strokes, a 7-year-old girl who didn't respond to medication had surgery, and a 24-year-old woman with worsening headaches had surgery to unblock an artery. These cases emphasize the importance of recognizing moyamoya syndrome in Noonan syndrome patients and the need for early surgical intervention to prevent further complications.

Ball, A. J., Steinberg, G. K. and Elbers, J. (2016). "Quality of Life in Pediatric Moyamoya Disease." Pediatr Neurol 63: 60-65.

Moyamoya disease (MMD) can lead to strokes and may impact children's quality of life. This study surveyed 30 children aged 7 to 17 with moyamoya disease to compare their quality of life with healthy peers and those who had strokes. Results revealed that children with MMD had lower quality of life scores than healthy children and similar scores to chronically ill kids and those with strokes from other causes. Notably, there was no significant difference in quality of life between those who had a stroke and those who did not. These findings suggest that children with moyamoya disease may need mental health support, as their quality of life can be affected even with mild symptoms.

Choudhri, O., Shah, A., Basarab-Tung, J., Jaffe, R. A. and Steinberg, G. K. (2015). "Extracorporeal membrane oxygenation for cardiac arrest during moyamoya cerebral revascularization surgery: case report." J Neurosurg 123(3): 693-698.

A 51-year-old man with moyamoya disease experienced a cardiac arrest during surgery but was successfully treated with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) after CPR failed. This case highlights ECMO's potential in non-traditional settings for patients with brain issues. Despite its risks and costs, the patient recovered fully after 48 hours on ECMO, suggesting it can be a safe option for select neurosurgical patients.

Navarro, R., Chao, K., Gooderham, P. A., Bruzoni, M., Dutta, S. and Steinberg, G. K. (2014). "Less invasive pedicled omental-cranial transposition in pediatric patients with moyamoya disease and failed prior revascularization." Neurosurgery 10 Suppl 1: 1-14.

A new laparoscopic technique called omental-cranial transposition has been developed to treat moyamoya disease in children who haven't improved after previous surgeries. This method involves moving tissue from the omentum to the brain to enhance blood flow. In a study of three children aged 5 to 12, the procedure resulted in minimal blood loss and quick recovery, with all patients experiencing symptom resolution within three months and improved blood flow confirmed by follow-up imaging. This approach appears to be safer and more effective than traditional surgery for moyamoya disease.

Pandey, P. and Steinberg, G. K. (2011). "Outcome of repeat revascularization surgery for moyamoya disease after an unsuccessful indirect revascularization. Clinical article." J Neurosurg 115(2): 328-336.

Revascularization surgery for moyamoya disease is effective in preventing strokes, but some patients may need repeat surgeries due to inadequate blood flow from initial indirect procedures. This study reviewed 16 patients (ages 5-48) who underwent repeat surgery after ongoing symptoms. Following the repeat procedures, 80% of surviving patients were free from new strokes or symptoms, and imaging showed improved blood flow in most cases. These results indicate that repeat revascularization can effectively assist patients with insufficient blood flow after initial treatments, with the choice of procedure based on the condition of the blood vessels.

Miskinyte, S., Butler, M. G., Herve, D., Sarret, C., Nicolino, M., Petralia, J. D., Bergametti, F., Arnould, M., Pham, V. N., Gore, A. V., Spengos, K., Gazal, S., Woimant, F., Steinberg, G. K., Weinstein, B. M. and Tournier-Lasserve, E. (2011). "Loss of BRCC3 deubiquitinating enzyme leads to abnormal angiogenesis and is associated with syndromic moyamoya." Am J Hum Genet 88(6): 718-728.

Moyamoya is a rare blood vessel disorder that narrows the carotid arteries in the brain, leading to fragile collateral vessels and an increased risk of strokes. It can occur alone or with conditions like neurofibromatosis and Down syndrome, and is more common in Japan. Recent research identified an X-linked moyamoya syndrome in three families, characterized by moyamoya angiopathy, short stature, and distinct facial features. The study linked this syndrome to gene deletions and found that the gene BRCC3 is essential for blood vessel formation, suggesting that mutations in BRCC3 may contribute to moyamoya angiopathy.

Lee, M., Guzman, R., Bell-Stephens, T. and Steinberg, G. K. (2011). "Intraoperative blood flow analysis of direct revascularization procedures in patients with moyamoya disease." J Cereb Blood Flow Metab 31(1): 262-274.

Moyamoya disease narrows the main brain arteries, leading to strokes and bleeding, with surgery being the primary treatment. In a study of 292 patients who had 496 surgeries, we measured blood flow and vessel size. Average blood flow in a key artery was 4.4 mL/min before surgery and increased to 22.2 mL/min after bypass surgery. Children had lower blood flow than adults. Higher blood flow post-surgery was linked to better recovery, but very high flow rates increased the risk of stroke, bleeding, and temporary neurological issues. This data helps us understand the disease and the impact of surgery.

Pandey, P., Bell-Stephens, T. and Steinberg, G. K. (2010). "Patients with moyamoya disease presenting with movement disorder." J Neurosurg Pediatr 6(6): 559-566.

Moyamoya disease is a rare condition that narrows blood flow in the brain, usually causing mini-strokes or strokes, but it can also lead to movement disorders in children. This report highlights four pediatric patients who presented with movement issues, such as jerky movements and limb shaking, out of 446 treated patients. Brain scans showed reduced blood flow in the frontal brain area, and three had the disease on both sides. After undergoing surgery to improve blood flow, all four patients fully recovered, with most showing normal blood flow in follow-up scans. This underscores that movement disorders can be a rare symptom of moyamoya disease, and the surgery was effective in their treatment.

Guzman, R. and Steinberg, G. K. (2010). "Direct bypass techniques for the treatment of pediatric moyamoya disease." Neurosurg Clin N Am 21(3): 565-573.

Moyamoya is an increasingly recognized cause of stroke in children and adults. Identification of the disease early in its course with prompt institution of therapy is critical to providing the best outcome for patients. Revascularization surgery seems to be effective in preventing stroke in moyamoya, with direct techniques providing durable protection when performed at experienced centers.

Guzman, R., Lee, M., Achrol, A., Bell-Stephens, T., Kelly, M., Do, H. M., Marks, M. P. and Steinberg, G. K. (2009). "Clinical outcome after 450 revascularization procedures for moyamoya disease. Clinical article." J Neurosurg 111(5): 927-935.

Researchers at Stanford University Medical Center studied 329 patients with moyamoya disease (MMD) treated surgically between 1991 and 2008 to understand its characteristics and long-term outcomes in North America. The study included 233 adults (average age 39.5) and 96 children (average age 10.1), with most undergoing surgery to improve blood flow. Over an average follow-up of 4.9 years, the complication rate was low (3.5%) and the mortality rate was very low (0.7%), with a 5.5% chance of stroke or death within five years. Additionally, 91.8% of patients with temporary stroke-like symptoms were symptom-free after one year, and overall quality of life significantly improved. The results indicate that revascularization surgery for MMD is low-risk, effective in preventing future strokes, and enhances patients' quality of life.

Veeravagu, A., Guzman, R., Patil, C. G., Hou, L. C., Lee, M. and Steinberg, G. K. (2008). "Moyamoya disease in pediatric patients: outcomes of neurosurgical interventions." Neurosurg Focus 24(2): E16.

Surgical treatments for moyamoya disease (MMD) in children include direct, indirect, and combined methods, all of which have proven effective, but no study has shown one to be superior. This review analyzes various studies, highlighting results from different hospitals. Direct methods can quickly improve blood flow and reduce stroke risk but may not be suitable for all children due to their complexity. Indirect methods are also effective but may take longer to show results. Overall, it's unclear which technique is best, as most studies involved small patient groups and varied success measures. More extensive research is needed to understand the pros and cons of each technique for pediatric patients.

Karzmark, P., Zeifert, P. D., Tan, S., Dorfman, L. J., Bell-Stephens, T. E. and Steinberg, G. K. (2008). "Effect of moyamoya disease on neuropsychological functioning in adults." Neurosurgery 62(5): 1048-1051; discussion 1051-1042.

Moyamoya disease is a brain blood vessel disorder that leads to the closure of key vessels and the formation of abnormal blood vessels. This study evaluated 36 adults with confirmed moyamoya disease using neuropsychological tests before surgery. While overall cognitive performance was normal, significant difficulties were noted in executive functioning, with 31% of patients showing some cognitive impairment—four with moderate to severe issues. Memory and intelligence were largely unaffected, and some patients reported mild to moderate depression. These results suggest that moyamoya disease can impact cognition in adults, but the effects are generally less severe than in children, highlighting the need for further research on brain function.

Golby, A. J., Marks, M. P., Thompson, R. C. and Steinberg, G. K. (1999). "Direct and combined revascularization in pediatric moyamoya disease." Neurosurgery 45(1): 50-58; discussion 58-60.

Surgical revascularization for moyamoya disease can improve neurological outcomes. A study on direct revascularization in 12 pediatric patients (ages 5 to 17) found that all patients stabilized or improved after surgery, with no new strokes or ischemic lesions. Follow-up showed significant enhancements in cerebral blood flow. This approach is effective, especially for children who did not benefit from previous treatments.

Wang, M. Y. and Steinberg, G. K. (1996). "Rapid and near-complete resolution of moyamoya vessels in a patient with moyamoya disease treated with superficial temporal artery-middle cerebral artery bypass." Pediatr Neurosurg 24(3): 145-150.

Surgical revascularization can improve moyamoya vessels in children, but clear evidence of near-complete resolution has been rare. In a case involving a 5-year-old boy who underwent a specific surgical procedure, he showed near-complete resolution of moyamoya vessels and significant improvement in brain blood flow. This suggests that the resolution of these vessels may indicate successful surgical outcomes.

Moyamoya Disease and Outcomes

Tigchelaar, S. S., Wang, A. R., Vaca, S. D., Li, Y. and Steinberg, G. K. (2024). "Incidence and Outcomes of Posterior Circulation Involvement in Moyamoya Disease." Stroke 55(5): 1254-1260.

A study of 770 patients with moyamoya disease (MMD) found that 41.1% had posterior circulation moyamoya disease (PCMMD), with severity ranging from mild to severe. Those with more severe PCMMD faced higher postoperative complications and worse functional outcomes. Over an average follow-up of six years, 12.6% showed new or worsening PCMMD, with significant progression influenced by factors like pre-existing disease status, tobacco use, and hypertension. These results highlight the importance of monitoring PCMMD in MMD patients due to its potential impact on health outcomes.

Abhinav, K., Lee, A. G., Pendharkar, A. V., Bigder, M., Bet, A., Rosenberg-Hasson, Y., Cheng, M. Y. and Steinberg, G. K. (2024). "Comprehensive Profiling of Secreted Factors in the Cerebrospinal Fluid of Moyamoya Disease Patients." Transl Stroke Res 15(2): 399-408.

Moyamoya disease (MMD) causes blockage of internal carotid arteries, leading to ischemic and hemorrhagic events. This study examined cerebrospinal fluid (CSF) from 71 MMD patients (37 ischemic, 34 hemorrhagic) and 32 controls, focusing on 62 secreted factors. It found 41 elevated molecules, including PDGF-BB and PAI-1, in both MMD types. Several interleukins and chemokines were newly associated with MMD. Pathway analysis revealed shared inflammatory activation and suppressed lipid signaling. IL-13 and IL-2 correlated negatively with preoperative blood flow, while seven factors correlated positively with postoperative revascularization. These elevated factors may play a role in MMD and serve as potential therapeutic targets.

This study evaluated the impact of surgery on cerebrovascular reserve (CVR) in children with Moyamoya disease. Analyzing data from 32 patients, researchers found that CVR significantly increased in the middle cerebral artery after surgery, from 6.9 to 16.5 mL of blood per 100 grams of brain tissue per minute. Children with the best blood flow outcomes had higher CVR, while the type of surgical bypass did not affect the improvement. The acetazolamide test effectively measures CVR enhancement post-surgery.

Church, E. W., Qaiser, R., Bell-Stephens, T. E., Bigder, M. G., Chow, E. K., Han, S. S., El-Sayed, Y. Y. and Steinberg, G. K. (2021). "Pregnancy after direct cerebral bypass for moyamoya disease." J Neurosurg 134(1): 10-16.

This study assessed the health outcomes of women with Moyamoya disease (MMD) who became pregnant after cerebral bypass surgery at Stanford Medical Center. Among 71 pregnancies in 56 women, post-surgery pregnancies showed low complication rates, with only 5 cases (8%) of temporary strokes and no confirmed strokes. In contrast, pregnancies before surgery had higher rates of temporary strokes (25%) and confirmed strokes (17%). Complications like preeclampsia occurred in 13% of pregnancies, and the cesarean delivery rate was 39%. Overall, the findings indicate that pregnancies after bypass surgery are generally safe, highlighting the need for collaboration between neurosurgeons and obstetricians for optimal care.

Teo, M., Furtado, S., Kaneko, O. F., Azad, T. D., Madhugiri, V., Do, H. M. and Steinberg, G. K. (2020). "Validation and Application for the Berlin Grading System of Moyamoya Disease in Adult Patients." Neurosurgery 86(2): 203-212.

This study assessed a new grading system for moyamoya disease (MMD) symptoms in 96 patients to predict surgical outcomes. The system categorized symptoms as mild, moderate, or severe, correlating well with clinical symptoms and postoperative results. After surgery, 33% of mild cases showed symptoms, compared to 92% of moderate and 100% of severe cases. A small percentage of mild cases experienced new brain damage or bleeding, with higher rates in moderate and severe cases. Overall, the grading system effectively stratifies preoperative symptoms and predicts new ischemic changes and strokes post-surgery.

Abhinav, K., Furtado, S. V., Nielsen, T. H., Iyer, A., Gooderham, P. A., Teo, M., Lee, J., Han, S. S. and Steinberg, G. K. (2020). "Functional Outcomes After Revascularization Procedures in Patients With Hemorrhagic Moyamoya Disease." Neurosurgery 86(2): 257-265.

This study assessed long-term outcomes in 104 patients with hemorrhagic moyamoya disease (MMD) who underwent surgical revascularization over 26 years. The average age was 38, and most patients (91.3%) received a direct bypass. Over an average follow-up of 61.4 months, 7.7% experienced rebleeding, with a rate of 1.9% per year, and the average modified Rankin scale (mRS) score improved from 1.3 to 1.1. The findings support surgical revascularization, especially direct bypass methods, as the rebleeding rate was significantly lower than natural rates.

Elbers, J., Armstrong, D., Benseler, S. M., Dlamini, N., Steinberg, G. K. and Yeom, K. W. (2018). "The Utility of Collaterals as a Biomarker in Pediatric Unilateral Intracranial Arteriopathy." Pediatr Neurol 78: 27-34.

This study explored whether children with unilateral intracranial arteriopathy and lenticulostriate collaterals have different vascular outcomes than those without. Analyzing imaging results from 44 children (average age 8.2 years), researchers found similar progression rates after about 25 months for the collateral group (50%) and 23 months for the non-collateral group (37.5%). The collateral group was linked to asymptomatic presentations, while the non-collateral group showed improvement or mixed results. Collaterals were significant predictors of vascular outcomes, indicating they could serve as useful imaging biomarkers for patient differentiation.

Teo, M., Johnson, J. N., Bell-Stephens, T. E., Marks, M. P., Do, H. M., Dodd, R. L., Bober, M. B. and Steinberg, G. K. (2016). "Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies." J Neurosurg Pediatr 25(6): 717-723.

Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder characterized by very short stature and severe small head size, often affecting brain blood vessels. This study reviewed ten MOPD II patients who underwent surgery between 2005 and 2012, including five with moyamoya disease (MMD) and two with brain aneurysms. Most patients had symptoms like temporary strokes, with average ages of 9 years for MMD and 15.5 years for aneurysms. Despite some complications, most recovered to their previous neurological state during an average follow-up of nearly six years, indicating that surgeries for MOPD II can yield positive long-term outcomes at specialized centers.

Bruzoni, M., Steinberg, G. K. and Dutta, S. (2016). "Laparoscopic harvesting of omental pedicle flap for cerebral revascularization in children with moyamoya disease." J Pediatr Surg 51(4): 592-597.

The omentum is ideal for revascularizing extraperitoneal wounds, and laparoscopic techniques may reduce complications associated with traditional harvesting methods. This study reviewed seven children who underwent laparoscopic omental flap mobilization for cerebral revascularization in moyamoya disease, noting one intraoperative and one postoperative complication. All patients achieved partial to complete symptom relief and showed adequate intracranial revascularization on angiography, suggesting that this approach is feasible and could be used for other conditions.

Khan, N., Achrol, A. S., Guzman, R., Burns, T. C., Dodd, R., Bell-Stephens, T. and Steinberg, G. K. (2012). "Sex differences in clinical presentation and treatment outcomes in Moyamoya disease." Neurosurgery 71(3): 587-593; discussion 593.

Moyamoya (MM) disease, more prevalent in females, was examined in 430 patients undergoing 717 revascularization procedures over 19 years. Females were more likely to experience preoperative transient ischemic attacks but showed similar neurological improvement post-surgery compared to males. However, females had a higher 5-year risk of adverse postoperative events (11.4%) than males (5.3%), suggesting greater postoperative risks despite similar neurological benefits from surgery.

Researchers at Stanford University Medical Center studied 329 patients with Moyamoya disease (MMD) treated between 1991 and 2008 to assess its characteristics and treatment outcomes in North America. Most patients underwent direct revascularization surgery, which had a low complication rate of 3.5% and a mortality rate of 0.7%. After surgery, 91.8% of those who had temporary strokes were symptom-free after a year, and patients reported significant improvements in quality of life. The results suggest that revascularization surgery is safe and effective for preventing future strokes in symptomatic MMD patients.

Direct and Indirect Bypasses for Moyamoya Disease

Gauden, A. J. and Steinberg, G. K. (2024). "Direct and indirect microvascular revascularization in the setting of moyamoya disease." J Clin Neurosci 119: 112.

Moyamoya disease causes blockages in the brain's blood vessels and currently has no effective endovascular treatments, making surgical revascularization the main option. A case involving a 40-year-old woman who underwent successful direct revascularization showed no further strokes post-surgery. Our findings suggest that younger patients with good collateral blood flow before surgery have better outcomes, highlighting the importance of skilled surgical techniques in reducing stroke risk.

Li, Y., Wang, A. R. and Steinberg, G. K. (2022). "Safety and Efficacy of Induced Hypertension and Hypervolemia in Preventing Neurologic Complications After Combined Direct and Indirect Bypass in Hemorrhagic-Onset Moyamoya Disease." World Neurosurg 160: e381-e387.

This study assessed the safety and effectiveness of induced hypertension and hypervolemia (IHH) during surgery for hemorrhagic-onset moyamoya disease (HOMMD) in 122 patients treated between 1987 and 2019. Among 203 procedures, there were 19 transient neurological events and a few ischemic and hemorrhagic complications, with no significant differences between those receiving IHH therapy and those who did not. The results suggest that while IHH may help patients with ischemic symptoms, it may not be necessary for those with hemorrhagic presentations.

Nielsen, T. H., Abhinav, K., Sussman, E. S., Han, S. S., Weng, Y., Bell-Stephens, T., Cnrn, Heit, J. J. and Steinberg, G. K. (2021). "Direct versus indirect bypass procedure for the treatment of ischemic moyamoya disease: results of an individualized selection strategy." J Neurosurg 134(5): 1578-1589.

This study evaluated the effectiveness of direct versus indirect bypass surgery for ischemic moyamoya disease (iMMD) in 138 patients treated between March 2016 and June 2018. Direct bypass was performed on 133 patients and indirect bypass on 62, with stroke rates of 4.7% and 6.8%, respectively, showing no significant difference. However, direct bypass resulted in better blood flow restoration and a trend toward greater patient improvement after six months. The authors concluded that direct bypass is the preferred treatment for iMMD.

Leuze, C., Goubran, M., Barakovic, M., Aswendt, M., Tian, Q., Hsueh, B., Crow, A., Weber, E. M. M., Steinberg, G. K., Zeineh, M., Plowey, E. D., Daducci, A., Innocenti, G., Thiran, J. P., Deisseroth, K. and McNab, J. A. (2021). "Comparison of diffusion MRI and CLARITY fiber orientation estimates in both gray and white matter regions of human and primate brain." Neuroimage 228: 117692.

Diffusion MRI (dMRI) is a non-invasive method for mapping brain fiber orientations, but it relies on indirect measurements. This study enhances dMRI interpretation by comparing it with optical imaging of labeled brain fibers in cleared tissue. It finds a mean angular difference of 19 degrees in fiber orientation estimates from human thalamus samples and shows that blood vessel structures do not significantly affect dMRI results. Overall, this research improves the integration of dMRI and CLARITY techniques for better understanding brain structure.

Ahmed, S. U., Lee, H. and Steinberg, G. K. (2021). "Commentary: Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease." Neurosurgery 89(2): E114-E115.

This study compared direct and indirect surgical procedures for adults with ischemic moyamoya disease (MMD) in North America. Analyzing 95 patient records from 1984 to 2018, researchers found early complications in 3.5% of direct bypass patients and 8.6% of indirect bypass patients, with no significant difference. While both methods had similar long-term outcomes, direct revascularization was associated with fewer combined ischemic and hemorrhagic events. Overall, both approaches are comparable in safety and effectiveness, but direct revascularization may reduce complications.

Church, E. W., Bell-Stephens, T. E., Bigder, M. G., Gummidipundi, S., Han, S. S. and Steinberg, G. K. (2020). "Clinical Course of Unilateral Moyamoya Disease." Neurosurgery 87(6): 1262-1268.

This study analyzed the progression of unilateral moyamoya disease (MMD) in 217 patients treated from 1991 to 2017, with an average follow-up of 5.8 years. About 8.3% of patients experienced worsening on the opposite side, with 3.7% requiring surgery. Factors like initial blockage severity and high cholesterol were linked to this progression. The findings suggest a lower progression rate than previously reported, recommending yearly noninvasive screenings and indicating potential benefits of statin therapy for MMD management.

Teo, M. K., Madhugiri, V. S. and Steinberg, G. K. (2017). "Editorial: Direct versus indirect bypass for moyamoya disease: ongoing controversy." J Neurosurg 126(5): 1520-1522.

In this issue of the Journal of Neurosurgery, Macyszyn and colleagues claim that direct revascularization for moyamoya disease has worse outcomes than indirect and combined techniques. However, the commentary argues that direct revascularization is effective, with lower long-term stroke risks and immediate blood flow improvements. The authors suggest considering both methods for pediatric cases, call for a randomized controlled trial, and reference a recent study supporting direct revascularization, concluding that direct bypass is preferred for most patients, while indirect procedures may be suitable for young children or specific cases.

Teo, M., Johnson, J. and Steinberg, G. K. (2017). "Strategies for and Outcome of Repeat Revascularization Surgery for Moyamoya Disease: An American Institutional Series." Neurosurgery 81(5): 852-859.

This study evaluated repeat revascularization outcomes in moyamoya disease (MMD) patients with prior indirect or direct bypass surgeries. Among 765 patients treated from 1991 to 2014, 57 required repeat procedures (38 indirect and 19 direct), with repeat rates of 4% for indirect and 1% for direct bypasses. Both groups had similar surgery intervals and rates of repeat procedures due to transient ischemic attacks. Over 50% of repeat surgeries were direct, aimed at improving blood flow. After nearly five years, over 80% of patients remained well and free from stroke symptoms, concluding that repeat revascularization is safe and effective, with higher repeat rates for indirect bypasses.

Liu, J. J. and Steinberg, G. K. (2017). "Direct Versus Indirect Bypass for Moyamoya Disease." Neurosurg Clin N Am 28(3): 361-374.

Moyamoya disease is a progressive occlusive vasculopathy affecting the supraclinoid internal carotid arteries and Circle of Willis, leading to collateral vessel formation, cerebral ischemia, and potential intracerebral hemorrhage. Surgical revascularization is the primary treatment, utilizing direct, indirect, and combined techniques. This discussion covers the available revascularization options and our perspectives on managing patients with moyamoya disease.

Feroze, A. H., Kushkuley, J., Choudhri, O., Heit, J. J., Steinberg, G. K. and Do, H. M. (2015). "Development of arteriovenous fistula after revascularization bypass for Moyamoya disease: case report." Neurosurgery 11 Suppl 2: E202-206.

Moyamoya disease, a rare condition affecting brain blood flow, is often treated with surgical bypass techniques. This report describes a 51-year-old woman who successfully underwent bypass surgery but later developed a new arteriovenous fistula at the surgery site, a first-of-its-kind case. Despite this complication, she had no neurological deficits or symptoms. The fistula likely formed from the reopening of a previously blocked vein. This case underscores the potential for arteriovenous fistula formation after bypass surgery and the need for careful treatment evaluation.

Researchers developed a minimally invasive technique for harvesting an omental flap that maintains its blood supply to treat children with moyamoya disease who had ongoing symptoms despite previous surgeries. Applied to three patients (ages 5-12), the method resulted in minimal blood loss, quick recovery (discharge within 3 to 5 days), and resolution of symptoms within three months. Follow-up imaging confirmed improved blood flow and successful restoration of targeted areas, demonstrating the technique's efficiency and effectiveness.

Pandey, P. and Steinberg, G. K. (2011). "Neurosurgical advances in the treatment of moyamoya disease." Stroke 42(11): 3304-3310.

Moyamoya disease affects brain blood vessels, leading to reduced blood flow. Recent advancements in treatment focus on restoring blood flow through direct and indirect surgical methods, supported by improved imaging techniques like MRI and PET scans. New approaches allow real-time monitoring during surgery, while indirect methods enhance blood supply by adding tissue to the brain's surface. Increased blood flow post-surgery can cause complications, emphasizing the need for careful monitoring. Overall, surgical restoration of blood flow is the preferred treatment.

Zhao, H., Yenari, M. A., Cheng, D., Sapolsky, R. M. and Steinberg, G. K. (2005). "Biphasic cytochrome c release after transient global ischemia and its inhibition by hypothermia." J Cereb Blood Flow Metab 25(9): 1119-1129.

Hypothermia protects the brain from damage caused by a lack of blood flow, though its mechanisms are not fully understood. In a study, researchers found that a protein called cytochrome c was released in two phases after inducing a lack of blood flow in cooled animals: an initial peak at 5 hours and a larger peak at 48 hours. Caspase activity, which contributes to brain damage, increased at 12 and 24 hours. A caspase blocker given after the lack of blood flow protected brain cells and halted the second peak of cytochrome c release. Overall, mild hypothermia helps protect the brain by reducing the later release of cytochrome c and lowering caspase activity.

Coert, B. A., Chang, S. D., Marks, M. P. and Steinberg, G. K. (2005). "Revascularization of the posterior circulation." Skull Base 15(1): 43-62.

Revascularization procedures in the brain's posterior circulation aim to prevent strokes caused by reduced blood flow, influenced by factors like the size of the posterior communicating artery. These procedures are for patients with persistent symptoms despite medication and those with ischemia from blocked vessels, especially in complex aneurysms. Treatment options include surgical and endovascular techniques, with careful management of blood pressure and brain function for safety. Studies indicate these interventions can improve symptoms in 60% to 100% of patients while reducing future stroke risk and maintaining low complication rates.

Jordan, J. E., Marks, M. P., Lane, B. and Steinberg, G. K. (1996). "Cost-effectiveness of endovascular therapy in the surgical management of cerebral arteriovenous malformations." AJNR Am J Neuroradiol 17(2): 247-254.

This study evaluated the cost-effectiveness of combining endovascular therapy with surgery for cerebral arteriovenous malformations (AVMs). It compared 25 patients receiving both treatments to 475 patients who had surgery alone. The average cost for the combined treatment was $71,366 (in 1992 dollars) versus $78,506 for surgery alone, resulting in a 9% savings per patient. The cost per quality-adjusted life-year was $6,734 for the combined approach compared to $9,814 for surgery alone, indicating up to 34% savings with endovascular therapy. Overall, the study found that combining these treatments offers significant financial benefits for AVM patients.

Book Chapter on Moyamoya Disease

Increasing awareness over the past 20 years of moyamoya symptoms and diagnosis has improved access to care for patients. Excellent surgical options are available to treat moyamoya, and surgery has been shown to be superior to medical therapy alone at preventing strokes, with excellent overall long term outcomes and minimal interruptions in lifestyle. We strongly advocate increased patient education and awareness of moyamoya, and encourage patients to be actively engaged with the treatment team to optimize long- term outcomes.

Read the full chapter here

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