Imaging and epidemiology of Moyamoya Vasculopathy: Case report and brief review

Case Report

David C. Lauzier¹, BS; Kristin P. Guilliams^1,2,3, MD, MSCI; Akash P. Kansagra^1,2,4, MD, MS.

Mallinckrodt Institute of Radiology, Washington University School of Medicine
Department of Neurology, Washington University School of Medicine
Department of Pediatrics, Washington University School of Medicine
Department of Neurological Surgery, Washington University School of Medicine

Corresponding Author:
Corresponding Author: David C. Lauzier, dlauzier@wustl.edu, (828) 578-9926 (ORCID
0000-0003-2825-3360). 510 S Kingshighway Blvd, St. Louis, MO 63110.

Any redistribution or reproduction of part or all of the contents in any form is prohibited other than the following:

you may print or download to a local hard disk extracts for your personal and non-commercial use only
you may copy the content to individual third parties for their personal use, but only if you acknowledge the website as the source of the material

You may not, except with our express written permission, distribute or commercially exploit the content. Nor may you transmit it or store it in any other website or other form of electronic retrieval system.

Case description

A 10-year-old girl with trisomy 21, epilepsy, and Moyamoya syndrome treated with prior encephaloduroarteriomyosynangiosis (EDAMS) presented to the emergency department following a three-week course of gait instability, short-term memory deficits, and slurred speech accompanied by intermittent left arm weakness and staring spells. Basic metabolic panel and complete blood count values collected upon admission were all within expected ranges. Her neurologic examination demonstrated 5/5 strength in both upper and lower extremities. Her neurological workup included magnetic resonance imaging and cerebral catheter angiography, which revealed imaging findings that are classically found in moyamoya vasculopathy (Figure 1). The patient’s neurologic status remained stable. For prevention of ischemic events related to her moyamoya syndrome, the patient was discharged with low-dose aspirin.

Discussion:

Moyamoya vasculopathy comprises chronic, progressive occlusion of the distal internal carotid artery and proximal anterior and middle cerebral arteries, which results in gradual development of lenticulostriate collateral pathways around the sites of occlusion that produce a characteristic “puff of smoke” appearance. Symptoms can be unilateral or bilateral, with unilateral disease typical of moyamoya syndrome¹. Moyamoya vasculopathy in the setting of associated conditions is termed moyamoya syndrome, while moyamoya vasculopathy in the absence of underlying conditions or risk factors is termed moyamoya disease. Moyamoya disease is most common in patients of East Asian descent. Moyamoya syndrome occurs at elevated rates in patients with trisomy 21 (3800/100,000 prevalence)^{2, 3} and neurofibromatosis 1 (NF1, 600/100,000 prevalence)⁴ (Table 1). Sickle cell disease (SCD) leads to increased rates of moyamoya vasculopathy and ischemic events, though heterogeneous definitions of vasculopathy employed in past studies have limited precise estimates of the prevalence of moyamoya vasculopathy secondary to SCD⁵ . Indeed, moyamoya vasculopathy is observed in up to 13-30% of patients with SCD that undergo cerebral angiography^1,6,7. In this population, arterial changes consistent with moyamoya are the product of excessive intimal hyperplasia and chronic thrombotic processes, and may be related to severity and duration of anemia^7-9. Two recent studies in African populations have found high prevalence rates of over 50% of children with SCD^9,10. Thus, the prevalence of moyamoya vasculopathy may be dependent on access to treatment of sickle cell disease early in life. Finally, moyamoya may be driven by SCD severity, as SCD cure via stem cell transplant has been reported to halt progression of vasculopathy¹¹.

Recent research has clarified the biological basis for the associations between several conditions and moyamoya syndrome or disease. The association with trisomy 21 is likely due to chromosome 21 encoding for proteins involved in arterial physiology including superoxide dismutase 1, interferon-γ receptor, cystathionine β-synthase, and the α chains of type IV collagen^12,13. Similarly, the association with neurofibromatosis type 1 is thought to result from proximity between the familial moyamoya disease gene (RNF213) mapped to 17q25.2 and the NF1 gene mapped to 17q11.2 ¹⁴. The increased prevalence of moyamoya disease in East Asian populations is believed to reflect the prevalence of the RNF213 gene mutant allele, an important susceptibility gene of familial moyamoya disease that demonstrates an autosomal dominant pattern of inheritance with low penetrance¹⁵. In non-East Asian populations, the DIAPH1 gene has been recently identified as a risk gene for sporadic moyamoya disease¹⁶.

There are several additional risk factors for moyamoya vasculopathy. Age is a factor, as moyamoya disease presents with a bimodal age distribution with peaks at approximately 10 and 40 years of age¹⁷. Moyamoya disease also occurs at an approximately two-fold higher rate in females than males¹⁷. In Caucasian populations, moyamoya disease occurs more frequently in patients with autoimmune diseases¹⁸. Prior radiation therapy can also be a predisposing factor¹⁹. For example, recent studies have indicated a higher incidence of post-radiation arteriopathy in children following proton beam radiation, with Bhattachayra et al. reporting large vessel arteriopathy in 22% of patients with post-radiation vascular imaging available²⁰. A systematic review identified post-radiation vasculopathy in 5% – 20% of patients that underwent proton and photon radiation, though some observed changes reflective of minor focal arteriopathic changes of the anterior cerebral artery, middle cerebral artery, and internal carotid artery in distinction to true Moyamoya syndrome^21,22. Finally, a prospective trial identified radiographic evidence of vessel stenosis after radiation in 36% of patients and need for revascularization procedures in 5% of patients²³. Interestingly, half of patients had abnormal screening MRAs prior to therapy, including tumor encasement of vessels, and a pre-radiation vessel abnormality was the strongest predictor of post-radiation vasculopathy.

In children with trisomy 21, careful monitoring of blood pressure may screen for children at risk who warrant further investigation prior to neurologic symptoms, as blood pressure has been noted to rise at routine visits up to a year prior to neurologic presentation in children with trisomy 21 and moyamoya compared to trisomy 21 children without moyamoya²⁴. Children with trisomy 21 and moyamoya have elevated rates of other comorbidities such as congenital heart disease, which may influence presentation and management²⁵. Additional signs of Moyamoya that may prompt workup include ophthalmologic findings including the morning glory disc anomaly²⁶. Clinically, moyamoya vasculopathy is associated with ischemic stroke in the anterior circulation²⁷. Pediatric patients with moyamoya vasculopathy may benefit from indirect vascular bypass procedures, including EDAMS, which confer long-term protection from later ischemic complications^28,29. Imaging, including vascular imaging, is an important consideration in children at risk of moyamoya with new neurological deficits. When available, screening with MRI and/or MRA is warranted in populations deemed high-risk for the development of moyamoya vasculopathy³⁰.

Acknowledgments: N/A

Conflict of Interest Statement:

APK is a consultant for Microvention and Penumbra. These relationships are not related to the content of this manuscript.

Author Contributions:

Designing/planning the manuscript: DCL, KPG, APK. Drafting the manuscript: DCL, KPG, APK. Critically reviewing and editing: KPG, APK. Approving the final version: DCL, KPG, APK.

References

Arias EJ, Derdeyn CP, Dacey RG, Jr., Zipfel GJ. Advances and surgical considerations in the treatment of moyamoya disease. Neurosurgery. Feb 2014;74 Suppl 1:S116-25. doi:10.1227/NEU.0000000000000229
Kumar P, Panigrahi I, Sankhyan N, Ahuja C, Goyadi PK. Down Syndrome with Moyamoya Disease: A Case Series. J Pediatr Neurosci. Apr-Jun 2018;13(2):201-204. doi:10.4103/jpn.JPN_116_17
Kainth DS, Chaudhry SA, Kainth HS, Suri FK, Qureshi AI. Prevalence and characteristics of concurrent down syndrome in patients with moyamoya disease. Neurosurgery. Feb 2013;72(2):210-5; discussion 215. doi:10.1227/NEU.0b013e31827b9beb
Vargiami E, Sapountzi E, Samakovitis D, et al. Moyamoya syndrome and neurofibromatosis type 1. Ital J Pediatr. Jun 21 2014;40:59. doi:10.1186/1824-7288-40-59
Guilliams KP, Fields ME, Dowling MM. Advances in Understanding Ischemic Stroke Physiology and the Impact of Vasculopathy in Children With Sickle Cell Disease. Stroke. Feb 2019;50(2):266-273. doi:10.1161/STROKEAHA.118.020482
Talahma M, Strbian D, Sundararajan S. Sickle cell disease and stroke. Stroke. Jun 2014;45(6):e98-100. doi:10.1161/STROKEAHA.114.005144
Yuan S, Jordan LC, Davis LT, et al. A cross-sectional, case-control study of intracranial arterial wall thickness and complete blood count measures in sickle cell disease. Br J Haematol. Feb 2021;192(4):769-777. doi:10.1111/bjh.17262
Merkel KH, Ginsberg PL, Parker JC, Jr., Post MJ. Cerebrovascular disease in sickle cell anemia: a clinical, pathological and radiological correlation. Stroke. Jan-Feb 1978;9(1):45-52. doi:10.1161/01.str.9.1.45
Elmahdi M, Fadalla T, Suliman M, Elsayed M, Awad Elhaj AM, Hussein H. Moyamoya syndrome and stroke among pediatric sickle cell disease patients in Sudan: A cross-sectional study. Ann Med Surg (Lond). Jun 2022;78:103815. doi:10.1016/j.amsu.2022.103815
Idro R, Boehme AK, Kawooya M, et al. Brain Magnetic Resonance Imaging and Angiography in Children with Sickle Cell Anaemia in Uganda in a Cross-Sectional Sample. J Stroke Cerebrovasc Dis. Apr 2022;31(4):106343. doi:10.1016/j.jstrokecerebrovasdis.2022.106343
Al-Jefri A, Siddiqui K, Al-Oraibi A, et al. Hematopoietic Stem Cell Transplantation Stabilizes Cerebral Vasculopathy in High-Risk Pediatric Sickle Cell Disease Patients: Evidence rom a Referral Transplant Center. J Hematol. Feb 2022;11(1):8-14. doi:10.14740/jh949
Kim HG, Lee SK, Lee JD. Characteristics of infarction after encephaloduroarteriosynangiosis in young patients with moyamoya disease. J Neurosurg Pediatr. Jan 2017;19(1):1-7. doi:10.3171/2016.7.PEDS16218
Zhang H, Zheng L, Feng L. Epidemiology, diagnosis and treatment of moyamoya disease. Exp Ther Med. Mar 2019;17(3):1977-1984. doi:10.3892/etm.2019.7198
Koc F, Yerdelen D, Koc Z. Neurofibromatosis type 1 association with moyamoya disease. Int J Neurosci. Aug 2008;118(8):1157-63. doi:10.1080/00207450801898279
Jang MA, Chung JW, Yeon JY, et al. Frequency and significance of rare RNF213 variants in patients with adult moyamoya disease. PLoS One. 2017;12(6):e0179689. doi:10.1371/journal.pone.0179689
Kundishora AJ, Peters ST, Pinard A, et al. DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease. JAMA Neurol. Aug 1 2021;78(8):993-1003. doi:10.1001/jamaneurol.2021.1681
Kim JS. Moyamoya Disease: Epidemiology, Clinical Features, and Diagnosis. J Stroke. Jan 2016;18(1):2-11. doi:10.5853/jos.2015.01627
Bower RS, Mallory GW, Nwojo M, Kudva YC, Flemming KD, Meyer FB. Moyamoya isease in a primarily white, midwestern US population: increased prevalence of autoimmune disease. Stroke. Jul 2013;44(7):1997-9. doi:10.1161/STROKEAHA.111.000307
Wu YH, Chang FC, Liang ML, et al. Incidence and long-term outcome of postradiotherapy moyamoya syndrome in pediatric patients with primary brain tumors: a single institute experience in Taiwan. Cancer Med. Aug 2016;5(8):2155-60. doi:10.1002/cam4.785
Bhattacharya D, Chhabda S, Lakshmanan R, et al. Spectrum of neuroimaging findings post-proton beam therapy in a large pediatric cohort. Childs Nerv Syst. Feb 2021;37(2):435-446. doi:10.1007/s00381-020-04819-9
Bavle A, Srinivasan A, Choudhry F, et al. Systematic review of the incidence and risk factors for cerebral vasculopathy and stroke after cranial proton and photon radiation for childhood brain tumors. Neurooncol Pract. Feb 2021;8(1):31-39. doi:10.1093/nop/npaa061
Nordstrom M, Felton E, Sear K, et al. Large Vessel Arteriopathy After Cranial Radiation Therapy in Pediatric Brain Tumor Survivors. J Child Neurol. Apr 2018;33(5):359-366. doi:10.1177/0883073818756729
Lucas JT, Jr., Faught AM, Hsu CY, et al. Pre- and Posttherapy Risk Factors for Vasculopathy in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Radiation Therapy. Int J Radiat Oncol Biol Phys. May 1 2022;113(1):152-160. doi:10.1016/j.ijrobp.2021.12.172
Santoro JD, Lee S, Mlynash M, et al. Blood Pressure Elevation and Risk of Moyamoya Syndrome in Patients With Trisomy 21. Pediatrics. Oct 2018;142(4)doi:10.1542/peds.2018-0840
See AP, Ropper AE, Underberg DL, Robertson RL, Scott RM, Smith ER. Down syndrome and moyamoya: clinical presentation and surgical management. J Neurosurg Pediatr. Jul 2015;16(1):58-63. doi:10.3171/2014.12.PEDS14563
Wang YY, Zhou KY, Ye Y, et al. Moyamoya Disease Associated With Morning Glory Disc Anomaly and Other Ophthalmic Findings: A Mini-Review. Front Neurol. 2020;11:338. doi:10.3389/fneur.2020.00338
Cramer SC, Robertson RL, Dooling EC, Scott RM. Moyamoya and Down syndrome. Clinical and radiological features. Stroke. Nov 1996;27(11):2131-5. doi:10.1161/01.str.27.11.2131
Riordan CP, Storey A, Cote DJ, Smith ER, Scott RM. Results of more than 20 years of follow-up in pediatric patients with moyamoya disease undergoing pial synangiosis. J Neurosurg Pediatr. Mar 1 2019:1-7. doi:10.3171/2019.1.PEDS18457
Terrell D, Savardekar AR, Whipple SG, Dossani RH, Spetzler RF, Sun H. Cerebral evascularization for Moyamoya Syndrome Associated with Sickle Cell Disease: A Systematic Review of the Literature on the Role of Extracranial-Intracranial Bypass in Treating Neurologic Manifestations of Pediatric Patients with Sickle Cell Disease. World Neurosurg. May 2020;137:62-70. doi:10.1016/j.wneu.2020.01.182
DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. Apr 28 2020;4(8):1554-1588. doi:10.1182/bloodadvances.2019001142
Ahn IM, Park DH, Hann HJ, Kim KH, Kim HJ, Ahn HS. Incidence, prevalence, and survival of moyamoya disease in Korea: a nationwide, population-based study. Stroke. Apr 2014;45(4):1090-5. doi:10.1161/STROKEAHA.113.004273
Wakai K, Tamakoshi A, Ikezaki K, et al. Epidemiological features of moyamoya disease in Japan: findings from a nationwide survey. Clin Neurol Neurosurg. Oct 1997;99 Suppl 2:S1-5. doi:10.1016/s0303-8467(97)00031-0
Baba T, Houkin K, Kuroda S. Novel epidemiological features of moyamoya disease. J Neurol Neurosurg Psychiatry. Aug 2008;79(8):900-4. doi:10.1136/jnnp.2007.130666
Miao W, Zhao PL, Zhang YS, et al. Epidemiological and clinical features of Moyamoya disease in Nanjing, China. Clin Neurol Neurosurg. Apr 2010;112(3):199-203. doi:10.1016/j.clineuro.2009.11.009
Chen PC, Yang SH, Chien KL, Tsai IJ, Kuo MF. Epidemiology of moyamoya disease in Taiwan: a nationwide population-based study. Stroke. May 2014;45(5):1258-63. doi:10.1161/STROKEAHA.113.004160
Birkeland P, Tharmabalan V, Lauritsen J, Ganesan V, Bjarkam CR, von Weitzel-Mudersbach P. Moyamoya disease in a European setting: a Danish population-based study. Eur J Neurol. Dec 2020;27(12):2446-2452. doi:10.1111/ene.14439
Kleinloog R, Regli L, Rinkel GJ, Klijn CJ. Regional differences in incidence and patient characteristics of moyamoya disease: a systematic review. J Neurol Neurosurg Psychiatry. May 2012;83(5):531-6. doi:10.1136/jnnp-2011-301387

Tables

Images

**Figure 1.** Cerebral angiography demonstrates steno-occlusive changes of the distal internal carotid arteries and proximal anterior and middle cerebral arteries (Panel a, orange arrow), with prominent lenticulostriate collateral channels that produced a “puff of smoke” appearance in the vicinity of the occluded arteries (Panel a, green arrow). T2 and T2/FLAIR imaging demonstrate hyperintense lesions in the centrum semiovale bilaterally, corresponding to chronic ischemic changes in the internal border zones (Panels b and c, red circles).

Lauzier Imaging and Epidemiology of Moyamoya Vasculopathy Case Report

Pediatr Stroke. 2022;4: 16-32

www.pediatricstrokejournal.com

Share this page on: