Moyamoya Disease in a Primarily White, Midwestern US Population
Increased Prevalence of Autoimmune Disease
Background and Purpose—Moyamoya disease is an uncommon, cerebrovascular occlusive disease of unknown pathogenesis. Previously described Moyamoya cohorts include predominantly Asian populations or ethnically diverse North American cohorts. To gain further insight into the pathogenesis of moyamoya, we examined clinical characteristics of a primarily white, Midwestern US population
Methods—Retrospective analysis of patients with angiographically confirmed moyamoya disease evaluated at our institution was performed. Prevalence of comorbidities, cerebrovascular risk factors, and autoimmune diseases were compared with the general population.
Results—Ninety-four patients with moyamoya were evaluated; 72.3% were female. Ethnic composition was primarily white (85%). A significantly higher prevalence of autoimmune disease was seen, particularly type 1 diabetes mellitus (8.5% versus 0.4% in the general population) and thyroid disease (17.0% versus 8.0% in the institutional general patient population). Hyperlipidemia was also increased (27.7% versus 16.3% in the general population).
Conclusions—This study of a unique, primarily white, Midwestern population of moyamoya patients demonstrates a significantly higher prevalence of autoimmune disease than in the general population. This supports a possible autoimmune component to the pathogenesis of moyamoya disease.
Moyamoya disease is an uncommon cerebrovascular condition characterized by stenosis or occlusion of the anterior circulation vasculature of the brain, with development of a network of collateral vessels resembling a puff of smoke on angiography.1 The epidemiology of moyamoya is well described in the literature among East Asian populations.2 Incidence of moyamoya disease in Japan has been reported as 0.35 per 100 000.3 Moyamoya has been described in all races and ethnicities worldwide,4 with a reported incidence in the Western United States of 0.086 per 100 000.5 Less is known about moyamoya among North Americans, in particular, whites. Recent North American studies have described the epidemiological characteristics of moyamoya in the Western United States, Missouri, and across the United States.5–7 However, these cohorts were diverse in their racial and ethnic make-up.
The pathogenesis of moyamoya is not well understood. A genetic role has been postulated, supported by the much higher incidence of moyamoya and familial moyamoya among Asians and Asian-Americans.5,8 However, the pathogenesis underlying moyamoya among other ethnicities, and within North American populations, is less clear. An immunologic basis has also been suggested, and recent reports have noted an association between moyamoya and autoimmune diseases, including Graves disease and systemic lupus erythematosus.9,10
Analysis of comorbidities may be helpful in determining the pathogenesis of moyamoya. However, this has been lacking in many studies. Among the US studies, stroke risk factors were assessed in 2, but no other comorbidities were assessed, other than well-known associated syndromes.5–7 We, therefore, sought to determine the epidemiological characteristics and comorbidities of the unique, primarily white, Midwestern US population of moyamoya patients at our institution.
After obtaining approval through our Institutional Review Board, a search of the clinical database was conducted for adult patients seen at our institution between 1979 and 2011, with a diagnosis of moyamoya disease. Retrospective chart review was conducted on patients who met inclusion criteria. Please see the online-only Data Supplement for details on inclusion/exclusion criteria and data collected. Comorbidity prevalences were compared with prevalences among the general population, taken from national statistics,11–13 except for thyroid disease prevalence, which was obtained from our institutional database (see the online-only Data Supplement).
Statistical analyses were performed using JMP statistical software (version 9.0.1, Cary, NC). Frequencies were calculated with means, medians, and SD. Comparisons between groups were made using χ2 test, and differences were considered significant with a P value <0.05.
Ninety-four patients met inclusion criteria. Female patients constituted 72.3%. The mean age at presentation was 34.5 years. Patient races included the following: white (85.1%), Asian (8.5%), black (5.3%), and Native American (1.1%). One patient had a family history of moyamoya (sibling). Patient demographics are shown in Table 1.
Anatomic Extent of Moyamoya
The majority (86.2%) of patients had bilateral disease; 13.8% of patients had unilateral disease (Table 1). Multiple anterior circulation arteries were involved in 67.0% of patients, with 15.9% of patients having isolated internal carotid artery disease. Isolated M1 stenosis at the origin, with moyamoya collaterals, was seen in 7.4% of patients. Stenosis extending to the posterior circulation was present in 10.6% of patients. Clinical moyamoya presentations are shown in Table 1.
Among conditions with a well-known moyamoya association, neurofibromatosis type 1 was found in 2 patients and Down syndrome was found in 1 patient.
Cerebrovascular Risk Factors
We found the presence of hyperlipidemia in 26.6% of patients, hypertension in 20.2%, current or previous tobacco use in 12.8%, type 2 diabetes mellitus in 5.3%, history of radiation to the head in 5.3%, history of head trauma in 4.3%, and fibromuscular dysplasia in 3.2% of patients. Among these, cerebrovascular risk factors were compared with US population prevalence (Table 2). Prevalence of hyperlipidemia was significantly higher in our cohort compared with the general population (P=0.003; χ2 test).12 However, our cohort did not display a significant difference among other factors.
We found a high prevalence of type 1 diabetes mellitus and thyroid disease among our moyamoya cohort (Table 2). Type 1 diabetes mellitus was noted in 8 patients (8.5%), significantly higher than in the general US population (0.4%; P<0.001, χ2 test).11 Thyroid diseases, specifically Graves disease (2.1%) and thyroiditis (14.9%), were significantly higher than in the institutional general population (0.43% and 7.6%; P=0.01 and 0.007, respectively, χ2 test).
Other autoimmune diseases included the following: autoimmune gastritis, Takayasu arteritis, primary biliary cirrhosis, juvenile rheumatoid arthritis, and thrombotic thrombocytopenic purpura (1 patient each). Twenty-one patients (22.3%) had autoimmune disease of any kind, significantly higher than the 3.2% estimated prevalence of autoimmune disease in the general population (P<0001, χ2 test).14 There was a higher preponderance of females among those with autoimmune disease (F:M ratio 2.5:1), and 90.5% were white.
We present here characteristics of a Midwestern moyamoya patient population, composed of a higher percentage of white patients than other US moyamoya studies5,7 (Table I in the online-only Data Supplement). The pathogenesis of moyamoya remains unclear. A genetic role has been theorized within East Asian countries where moyamoya is more common. However, less is known about the pathogenesis of moyamoya within white, North American patients.
An unusually high prevalence of autoimmune disease, particularly type 1 diabetes mellitus and thyroid disease, was present in our cohort, which may suggest an underlying autoimmune component to moyamoya. Elevated thyroid autoantibodies9 and endothelial cell autoantibodies15 have been found among moyamoya patients as well, lending further support to this theory.
A significantly higher rate of hyperlipidemia was seen in our moyamoya cohort than in the general population.12 The reason for this is unclear, although it is a known association with other occlusive vascular diseases, as well as untreated hypothyroidism.
Moyamoya presenting concurrently with another specific autoimmune disease has been described in multiple case reports in the literature. This is the first series to our knowledge in which autoimmune disease in general has been investigated among moyamoya patients and a higher overall prevalence observed. The study may be limited by referral bias of our tertiary care institution; ascertainment bias in determination of thyroid disease prevalence; and absence of age-, sex- and race-matching of data. Future studies directed toward assessment of the immune system may shed further light on the elusive pathogenesis of moyamoya and, perhaps, help clinicians better anticipate the possibility of one after the other is diagnosed.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.111.000307/-/DC1.
- Received November 28, 2012.
- Accepted March 15, 2013.
- © 2013 American Heart Association, Inc.
- Hallemeier CL,
- Rich KM,
- Grubb RL Jr.,
- Chicoine MR,
- Moran CJ,
- Cross DT III.,
- et al
- Kim SJ,
- Heo KG,
- Shin HY,
- Bang OY,
- Kim GM,
- Chung CS,
- et al
- El Ramahi KM,
- Al Rayes HM
- 11.↵National Diabetes Information Clearinghouse (NDIC), A service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH). National Diabetes Statistics, 2011. http://www.diabetes.niddk.nih.gov/dm/pubs/statistics/. Accessed July 15, 2012.
- 12.↵Division for Heart Disease and Stroke. Prevention, Centers for Disease Control and Prevention. Cholesterol Fact Sheet, 2012. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_cholesterol.htm. Accessed October 20, 2012.
- Schiller JS,
- Lucas JW,
- Ward BW,
- Peregoy JA
- Ogawa K,
- Nagahiro S,
- Arakaki R,
- Ishimaru N,
- Kobayashi M,
- Hayashi Y