Cong Han

Moyamoya Disease in China Its Clinical Features and Outcomes

Background and Purpose— Here we describe the clinical features and outcomes of patients with moyamoya disease who were surgically treated at a single institution in China. Methods— Our cohort included 802 patients with moyamoya disease. Demographic and clinical characteristics were obtained by retrospective chart review; follow-up information and outcome were obtained through clinical visits, telephone, or letter interview. We used the Kaplan-Meier methods to estimate stroke risk by treatment status. Results— The median age for the onset of symptoms was 28 (range, 0.5–77) years. Two definite peaks in age distribution were found. The ratio of women to men was 1:1 (398/404). Familial occurrence of moyamoya disease was 5.2%. The initial symptom was ischemia, hemorrhage, or others in 564, 113, and 125 patients, respectively. Twenty-nine of the 802 patients (3.6%) received conservative management. The remaining 773 patients (96.4%) underwent neurosurgical revascularization procedures, and 502 of these were bilateral. The median follow-up after surgery (n=773) or conservative management (n=26) was 26.3 months (range, 6.0–101.9 months). Most subsequent ischemic events appeared in the first 2 years after surgery. The Kaplan-Meier estimated stroke risk was 10.1% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 12.7% after surgery for all patients treated with surgical revascularization. Conclusions— This study on the clinical features of moyamoya disease in mainland China indicated bimodal incidence distribution with women-to-men ratios of 1:1 and lower rate of hemorrhages in adults compared with in children. Patients had low rates of postoperative ischemic or hemorrhagic strokes, and the majority of patients had preserved functional status after revascularization.

Moyamoya Disease in China

Background and Purpose— Here we describe the clinical features and outcomes of patients with moyamoya disease who were surgically treated at a single institution in China. Methods— Our cohort included 802 patients with moyamoya disease. Demographic and clinical characteristics were obtained by retrospective chart review; follow-up information and outcome were obtained through clinical visits, telephone, or letter interview. We used the Kaplan-Meier methods to estimate stroke risk by treatment status. Results— The median age for the onset of symptoms was 28 (range, 0.5–77) years. Two definite peaks in age distribution were found. The ratio of women to men was 1:1 (398/404). Familial occurrence of moyamoya disease was 5.2%. The initial symptom was ischemia, hemorrhage, or others in 564, 113, and 125 patients, respectively. Twenty-nine of the 802 patients (3.6%) received conservative management. The remaining 773 patients (96.4%) underwent neurosurgical revascularization procedures, and 502 of these were bilateral. The median follow-up after surgery (n=773) or conservative management (n=26) was 26.3 months (range, 6.0–101.9 months). Most subsequent ischemic events appeared in the first 2 years after surgery. The Kaplan-Meier estimated stroke risk was 10.1% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 12.7% after surgery for all patients treated with surgical revascularization. Conclusions— This study on the clinical features of moyamoya disease in mainland China indicated bimodal incidence distribution with women-to-men ratios of 1:1 and lower rate of hemorrhages in adults compared with in children. Patients had low rates of postoperative ischemic or hemorrhagic strokes, and the majority of patients had preserved functional status after revascularization.

Increased Thyroid Function and Elevated Thyroid Autoantibodies in Pediatric Patients With Moyamoya Disease: A Case-Control Study

Background and Purpose— The purpose of this study was to investigate whether thyroid function and thyroid autoantibodies were associated with the risk of moyamoya disease in pediatric subjects. Methods— Thyroid function and thyroid autoantibodies were evaluated in patients with moyamoya disease and control subjects, and their associations with moyamoya disease were estimated using multivariate analysis. Results— We included 114 pediatric patients and 114 healthy control subjects. The patients displayed higher prevalence of increased thyroid function and elevated thyroid autoantibodies in comparison with control subjects. These remained significant after multivariate adjustment; the ORs (95% CI) for increased thyroid function and evaluated thyroid autoantibodies were evaluated as 12.47 (1.55 to 100.51) and 4.33 (1.29 to 14.59), respectively. Conclusions— Increased thyroid function and elevated thyroid autoantibodies are associated with moyamoya disease and therefore monitoring of thyroid function and thyroid autoantibodies in patients with moyamoya disease is suggested, which might help to guide subsequent clinical management.

Clinical features, surgical treatment, and long-term outcome in pediatric patients with moyamoya disease in China.

Background: There was few detailed demographic and clinical data about Chinese patients with moyamoya disease. Here we describe the clinical features, surgical treatment, and long-term outcome of pediatric patients with moyamoya disease at a single institution in China. Methods: Our cohort included 288 pediatric patients with moyamoya disease. The demographic and clinical characteristics were obtained by retrospective chart review and long-term outcome was evaluated using the stroke status. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. The risk of subsequent stroke was determined using the Kaplan-Meier method. Results: The median age for the onset of symptoms was 8.0 years. The ratio of female to male patients was 1:1. Familial occurrence of moyamoya disease was 9.4%. The incidence of postoperative complications was 4.2%. Postoperative ischemic events were identified as predictors of unfavorable clinical outcome, while older age of symptom onset was associated with a favorable clinical outcome. The Kaplan-Meier estimate stroke risk was 5% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 9% after surgery for all patients treated with surgical revascularization. Overall, 86% of patients had an independent life with no significant disability. Conclusion: This long-term survey demonstrated that most surgically treated pediatric patients with MMD maintain good outcomes. Our results indicate that an early diagnosis and active intervention before the establishment of irreversible hemodynamic change are essential to achieve a favorable clinical outcome.

Association of a functional polymorphism in the MMP-3 gene with Moyamoya Disease in the Chinese Han population.

Background: Moyamoya disease (MMD) is an uncommon cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. The important role of genetic factors in the etiology and pathogenesis of MMD is being increasingly recognized. The study was designed to examine the association of single nucleotide polymorphisms in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) genes with MMD occurrence. Methods: A case-control study was performed. Five functional promoter polymorphisms in the MMP-2, MMP-3, MMP-9 and MMP-13 genes and a potentially functional promoter polymorphism in the TIMP-2 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. Their associations with MMD were analyzed by multivariate logistic regression. Results: In total, 208 definite patients with MMD (including 31 familial MMD, FMMD, patients) and 224 healthy subjects were recruited. The frequency of the MMP-3 5A/6A and 5A/5A genotypes was significantly lower in MMD patients (OR = 0.57, 95% CI 0.38–0.86, pcorr = 0.042) compared with healthy controls in a dominant genetic model. Significant differences of the MMP-3 5A/6A polymorphism were also detected between FMMD patients and controls both in the dominant genetic model (OR = 0.23, 95% CI 0.08–0.68, pcorr = 0.048) and the additive genetic model (OR = 0.24, 95% CI 0.08–0.69, pcorr = 0.048). Conclusion: The functional polymorphism in the MMP-3 promoter might be associated with susceptibility to both MMD and FMMD in the Chinese Han population. The findings need to be validated in further studies including more subjects from different populations.

Hemorrhagic Moyamoya Disease in Children Clinical, Angiographic features, and Long-Term Surgical Outcome

Background and Purpose— Here, we describe the clinical, angiographic characteristics, and long-term surgical outcome of hemorrhagic moyamoya disease in children. Methods— We retrospectively collected 374 consecutive children with moyamoya disease (hemorrhagic 30 and ischemic 344) between 2004 and 2012 in our hospital. The clinical and radiological characteristics of the hemorrhagic patients were retrospectively described and analyzed. All the hemorrhagic patients underwent encephalo-duro-arterio-synangiosis procedure. Digital subtraction angiography was performed to evaluate the efficacy of vascularization. Clinical follow-up outcomes were obtained through clinical visits, telephone, or letter interview. Results— In our study, the ratio of female to male patients in the hemorrhagic group was significantly higher than the ischemic group (2:1 versus 0.9:1; P<0.05). The most frequent hemorrhagic location was intraventricular hemorrhage (n=22, 73%). In addition, significantly greater dilatation of the anterior choroidal artery and the posterior communicating artery were seen in the hemorrhagic group (P<0.05). Good or fair vascularization were observed in all the 15 children with digital subtraction angiography follow-up. Clinical outcomes showed that 25 of 30 (83%) patients had no disability (modified Rankin scale score, 0 and 1); 1 patient (3.3%) died of recurrent hemorrhagic stroke. Conclusions— The presence of anterior choroidal artery and posterior communicating artery dilation may be associated with the bleeding episode in the children with hemorrhagic moyamoya disease. The encephalo-duro-arterio-synangiosis surgery can effectively increase the cerebral blood flow in children, which may decrease the incidence of recurrent hemorrhage.

Prospective Screening of Family Members with Moyamoya Disease Patients

Background Genetic factors play an important role in the pathogenesis of moyamoya disease (MMD). Previous studies concentrated on familial MMD patients. In this study, we focused on family members of sporadic MMD patients, and aimed to gain a clearer understanding of the role that genetic factors play in MMD. Methods The immediate family members of MMD patients were initially screened by transcranial Doppler sonography (TCD) and positive cases were verified by magnetic resonance angiography (MRA). Results From July 2011 to March 2013, there were 527 MMD patients managed in our hospital, including 38 familial MMD cases. In this study, 285 immediate family members of 245 sporadic MMD patients were screened. Another 41 cases of familial MMD cases were identified, which included 21 family members and 20 corresponding sporadic MMD patients who had family members confirmed positive with MMD. As a result, the proportion of familial MMD patients increased from 7% (38/527) to 15% (79/527) in this period. For the main segments of the circle of Willis, Kappa values between TCD and MRA for the anterior cerebral arteries, middle cerebral arteries and posterior cerebral arteries were 0.91, 0.72, and 0.47, respectively. Familial cases confirmed by our screening showed a significantly higher percentage of asymptomatic patients (57%) compared with 9% from the control group who had a clear family history before. Conclusions Familial MMD patients may account for a higher percentage among all cases than previously thought. Some family members of MMD patients may also have MMD, but not have any obvious symptoms. Routine screening should be implemented for all family members of MMD patients to improve the detection rate for this part of the patient base. TCD has a high diagnostic agreement with MRA for MMD. TCD may be the preferred choice for screening because it is inexpensive and safe.

Difference in Angiographic Characteristics Between Hemorrhagic And Nonhemorrhagic Hemispheres Associated with Hemorrhage Risk of Moyamoya Disease in Adults: A Self-Controlled Study.

BACKGROUND Here, we compare the angiographic characteristics of hemorrhagic and nonhemorrhagic hemispheres within the same adult patient with moyamoya disease (MMD) and identify the possible risk factors for initial and recurrent hemorrhage during the long-term follow-up period. METHODS We retrospectively collected and analyzed the clinical and angiographic data of 145 consecutive adults with hemorrhagic MMD between 2004 and 2011. Separate angiographic characteristics of the hemorrhagic and nonhemorrhagic hemispheres were analyzed based on digital subtraction angiography. Multivariate logistic regression analysis was used to study the risk factors related to initial hemorrhage. In addition, clinical follow-up for at least 5 years was obtained in all the 145 patients. Cox regression analysis was used to determine the predictors for the subsequent recurrent hemorrhagic strokes. RESULTS With regard to the 145 consecutive patients in our cohort, multivariate analysis indicated that the dilation grade of anterior choroidal artery (odds ratio [OR], 2.449; 95% confidence interval [CI], 1.617-3.862), the dilation grade of the posterior communicating artery (PComA) (OR, 1.491; 95% CI, 1.071-2.075), and the involvement of the posterior cerebral artery (OR, 4.623; 95% CI, 1.273-16.792) were significantly associated with initial hemorrhage. After a median follow-up of 6.33 ± 1.81 years, 20 of the 145 patients (13.8%) developed 22 recurrent episodes of hemorrhage. No significant correlation was found between rebleeding and the above significant factors associated with the initial hemorrhage. CONCLUSIONS Compared with the nonhemorrhagic hemispheres, hemorrhagic hemispheres are more prone to recurrent hemorrhage. Our case-control study showed the dilation of the anterior choroidal artery or posterior communicating artery, as well as the involvement of the posterior cerebral artery, is associated with the initial hemorrhage of MMD, but not for the episode of recurrent hemorrhage. Longer and more detailed clinical and angiographic follow-up are still needed to delineate the specific mechanism underlying the recurrent hemorrhage in hemorrhagic MMD.

Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes.

OBJECTIVE Debate exists regarding the merits and shortcomings of an indirect bypass procedure for treating adult patients with moyamoya disease (MMD). Considerable variation in neovascularization occurs among different organs in patients with diabetes mellitus. Here, the effect of encephaloduroarteriosynangiosis on MMD associated with Type 2 diabetes mellitus (T2DM) is evaluated. METHODS A retrospective and 1:2 matched case-control study was conducted in moyamoya patients with or without T2DM (n = 180). Postoperative collateral formations were graded according to the Modified Collateral Grading System that originated from the Matsushima Angiographic Stage Classification. Neurological function outcomes before and after the operation were evaluated according to the modified Rankin Scale. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. RESULTS There was no statistically significant difference in the constituent ratios of initial symptom and preoperative Suzuki stage between patients with and without T2DM. Progression of angiopathy around the circle of Willis was postoperatively observed in bilateral internal carotid arteries in both groups. Patients with T2DM had a higher postoperative Suzuki stage (p < 0.01) and more frequent development of collateral angiogenesis germinating from the external carotid after indirect revascularization procedures in the surgical cerebral hemisphere (82.7% vs 72.2%; p < 0.05). The extent of postoperative collateral formation in patients with diabetes mellitus was significantly higher (p < 0.01). Postoperative clinical improvement in the diabetes group was more common after revascularization procedures (p < 0.05), and the diabetes group had lower modified Rankin Scale scores (p < 0.05) in comparison with the nondiabetes group. Late postoperative stroke and posterior cerebral artery involvement were identified as predictors of unfavorable clinical outcome in both groups, while T2DM was associated with a favorable clinical outcome. CONCLUSIONS Encephaloduroarteriosynangiosis is an efficacious treatment for adult patients with MMD. Patients with T2DM could achieve better collateral circulation and clinical improvement following surgery.

Moyamoya disease presenting with subarachnoid hemorrhage: Clinical features and neuroimaging of a case series

Background. Hemorrhage is a major category of the clinical symptoms of moyamoya disease (MMD). Intracerebral and intraventricular hemorrhages are the most common hemorrhages in MMD, and subarachnoid hemorrhages (SAHs) are notably rare. There have only been a few previous case reports of this imaging manifestation. In the present study, we investigated the clinical and neuroimaging features of MMD patients who presented with SAH and sought to identify the possible causes of hemorrhage. Methods. The right and left cerebral hemispheres of each patient were identified as hemorrhagic or non-hemorrhagic. Each hemisphere was assessed for Suzuki stage, and dilatation and branch extension of the anterior choroidal artery (AChA) and posterior communicating artery (P-CoM) and for the degree of transdural anastomosis and posterior circulation compensation. Next, these data were statistically analyzed for correlations with the SAH events. Results. In 34 of 349 hemorrhagic MMD patients, the first episode of hemorrhage was a SAH, among which, 26 (76.5%) patients were women and there was only one pediatric patient. The Suzuki stage was not statistically correlated with the SAH events. There were also no correlations between SAH and dilatation or abnormal branching of the AChA and P-CoM. In contrast, SAH and transdural anastomosis were correlated. 25 of the 34 hemorrhagic hemispheres (73.5%) were positive for transdural anastomosis, and this number was 15 (44.1%) in the non-hemorrhagic hemispheres; this difference was statistically significant (P<0.05). Conclusions. SAH is an important type of hemorrhage in MMD patients and ranks as the fourth most common type after intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and ICH + IVH. It mainly occurs in adult women, and the rupture of the transdural anastomosis might be the main cause of this condition.