Xingju Liu

Long term outcome after conservative and surgical treatment of haemorrhagic moyamoya disease

Objective To investigate the long term outcomes after conservative and surgical treatment for haemorrhagic moyamoya disease. Methods 97 consecutive patients with haemorrhagic moyamoya disease from 1997 to 2009 were enrolled in this study (mean age 31±10 years; range 5–56 years). We reviewed the clinical charts and radiographs of patients at the first bleeding episode. Follow-up was obtained prospectively by questionnaires and radiographic examinations. Outcomes were compared based on initial treatment (conservative vs surgical). Results After a median follow-up of 7.1 years, 21 of the 97 (21.7%) patients developed a second episode of bleeding, and six patients (6.2%) died of intracranial rebleeding. The median interval from initial episode to subsequent rebleeding was 9.1 years (0.1–23.2 years). 17 of 43 (37.1%) conservatively treated patients and four of 54 (7.4%) surgically treated patients experienced a rebleeding event (OR 8.1; 95% CI 2.4 to 26.8; p<0.001). There was a difference in the Kaplan–Meier curve of rebleeding between the two groups (Breslow test p=0.047; log rank test p=0.05). The rebleeding ratio in patients who underwent direct bypass was lower than that in patients treated with indirect bypass alone (0% vs 28.5%, 95% CI 1.0 to 1.9; p=0.002). No significant correlation was found between rebleeding and the patients age, sex, location of haemorrhage, hypertension status or presence of cerebral aneurysm (p>0.05). Conclusions There is a high risk of rebleeding after the first haemorrhagic episode in Chinese patients with haemorrhagic moyamoya disease. Revascularisation surgery can improve regional blood flow and have greater efficacy at preventing rebleeding than conservative treatment.

Risk of cerebral arteriovenous malformation rupture during pregnancy and puerperium

Objective: To determine whether the risk of arteriovenous malformation (AVM) rupture is increased during pregnancy and puerperium. Methods: Participants included 979 female patients with intracranial AVM admitted to Beijing Tiantan Hospital between 1960 and 2010. Two neurosurgery residents reviewed medical records for each case. Of them, 393 patients with ruptured AVM between 18 and 40 years of age were used for case-crossover analysis. Number of children born and clinical information during pregnancy and puerperium were retrieved to identify whether AVM rupture occurred during this period. Results: Of the 979 women, 797 hemorrhages occurred during 25,578 patient-years of follow-up, yielding an annual hemorrhage rate of 3.11%. The annual AVM hemorrhage rate in patients aged 18 to 40 years (n = 579) was 2.78%, lower than the rate in other age groups (odds ratio = 0.75, 95% confidence interval 0.65–0.86, p < 0.05). Of the 393 patients with rupture of AVM aged 18 to 40 years, 12 hemorrhages occurred in 12 patients over 452 pregnancies, yielding a hemorrhage rate of 2.65% per pregnancy or 3.32% per year. Among the remaining 381 patients, 441 hemorrhages occurred during 10,627 patient-years of follow-up, yielding an annual hemorrhage rate of 4.14%. The odds ratio for rupture of AVM during pregnancy and puerperium, compared with the control period, was 0.71 (95% confidence interval 0.61–0.82). Conclusions: No increased risk of hemorrhage was found in patients with cerebral AVM during pregnancy and the puerperium. We therefore would not advise against pregnancy in women with intracranial AVM.

Intracranial hemorrhage from moyamoya disease during pregnancy and puerperium

To determine the incidence of hemorrhage among women with moyamoya disease (MMD) during pregnancy and puerperium.

Direct versus indirect bypasses for adult ischemic-type moyamoya disease: a propensity score–matched analysis

OBJECTIVE The optimal surgical modality for moyamoya disease (MMD) remains unclear. The aim of this study was to compare the surgical effects of direct bypass (DB) and indirect bypass (IB) in the treatment of adult ischemic-type MMD. METHODS Adult patients with ischemic-type MMD who underwent either DB or IB from 2009 to 2015 were identified retrospectively from a prospective database. Patients lost to follow-up or with a follow-up period less than 12 months were excluded. Recurrent stroke events and modified Rankin Scale (mRS) scores at the last follow-up were compared between the 2 surgical groups after 1:1 propensity score matching. RESULTS A total of 220 patients were considered, including 143 patients who underwent DB and 77 patients who underwent IB. After propensity score matching, 70 pairs were obtained. The median follow-up period was 40.5 months (range 14-75 months) in the DB group and 31.5 months (range 14-71 months) in the IB group (p = 0.004). Kaplan-Meier analysis showed that patients who received DB had a longer stroke-free time (mean 72.1 months) compared with patients who received IB (mean 61.0 months) (p = 0.045). Good neurological status (mRS score ≤ 2) was achieved in 64 patients in the DB group (91.4%) and 66 patients in the IB group (94.3%), but there was no significant difference (p = 0.512). CONCLUSIONS Although neurological function outcome was not determined by the surgical modality, DB is more effective in preventing recurrent ischemic strokes than IB for adult ischemic-type MMD.

Effects of different surgical modalities on the clinical outcome of patients with moyamoya disease: a prospective cohort study

OBJECTIVE Bypass surgery is the most common treatment for moyamoya disease (MMD), but there is controversy over which surgical modality is best. The objective of this study was to evaluate the clinical outcome of patients with MMD after undergoing different surgical modalities. METHODS A series of 696 consecutive MMD patients treated between June 2009 and May 2015 were screened in this prospective cohort study. Patients who did not undergo revascularization surgeries and those who underwent different surgical modalities in bilateral hemispheres were excluded. Finally, 529 patients who were observed for at least 12 months were included: 438 patients underwent unilateral surgery, and 91 patients underwent bilateral surgery. Of these, 241 patients underwent direct bypass (DB); 81, a combined bypass (CB); and 207, an indirect bypass (IB). Three clinical outcomes were evaluated and compared between surgical groups: recurrent stroke events, modified Rankin Scale (mRS) scores, and change in the main symptoms. RESULTS The mean follow-up period was 40 months. During the follow-up period, recurrent stroke was observed in 43 patients, including 15 patients with hemorrhage, 26 patients with ischemia (transient ischemic attack in 19 patients and infarction in 7 patients), and 2 patients with both hemorrhage and cerebral infarction. Kaplan-Meier analysis showed that patients who underwent a CB or DB had a longer ischemia-free time than those who underwent IB (p = 0.013); however, there was no significant difference in the hemorrhage-free time between the different surgical modalities (p = 0.534). A good neurological status (mRS score ≤ 2) was achieved in 495 patients (93.6%) and was significantly achieved by more children (98.2%) than adults (92.3%; p = 0.022). Surgical modalities were not significantly associated with outcome neurological status (p = 0.860). Moreover, improvement in symptoms was observed in 449 patients (84.9%) and was also significantly more common in children (93.0%) than in adults (82.7%; p = 0.006). No significant difference was observed between the different surgical modalities (p = 0.548). CONCLUSIONS CB and DB are more effective at preventing recurrent ischemic strokes than IB. However, there is no evidence that these 3 surgical modalities demonstrate significant differences in preventing recurrent hemorrhage.

Clinical Features, Surgical Treatment, and Long-Term Outcome in Elderly Patients with Moyamoya Disease

OBJECTIVE To elucidate the clinical features, surgical treatment, and long-term outcome in elderly patients with moyamoya disease (MMD). METHODS We retrospectively reviewed 87 elderly patients with MMD at Beijing Tiantan Hospital. Clinical features, radiologic findings, and outcomes were analyzed. RESULTS The mean age at diagnosis was 54.0 ± 3.7 years. Familial occurrence was 2.3%. Underlying vascular risk factors was 74.7%. Infarction was the most common symptom in elderly MMD (40.2%). Most patients presented with Suzuki stage 4 or 5 MMD (51.2%). Posterior cerebral artery involvement was observed in 22 (25.3%) patients. The incidence of postoperative infarction or hemorrhages was 6.9%. Diabetes was identified as a predictor of adverse postoperative events. During the average follow-up of 35.5 ± 22.2 months, rebleeding in patients with hemorrhagic MMD was higher than in those with ischemic MMD (P < 0.05). Whats more, the rate of perfusion improvement in surgically treated patients was higher than in conservatively treated patients 3 months after discharge (P < 0.05). CONCLUSIONS Infarction was the most common symptom in elderly MMD. More vascular risk factors, a higher grade of Suzuki stage, fewer familial cases, and posterior cerebral artery involvement were observed in elderly patients with MMD. Diabetes was a risk factor of postoperative events for elderly patients. Hemorrhagic MMD had a higher rate of rebleeding than the ischemic type. Although surgical revascularization procedures can improve cerebral perfusion, further study is needed to determine whether surgical revascularization is effective in elderly patients or with certain techniques.

Clinical Features of Hemorrhagic Moyamoya Disease in China

OBJECTIVE To elucidate the clinical features of patients with hemorrhagic moyamoya disease (MMD) in China. METHODS We retrospectively reviewed 471 patients with hemorrhagic MMD at Beijing Tiantan Hospital. Clinical features and radiologic findings were analyzed. RESULTS The mean age at diagnosis was 35.3 ± 11.5 years, with 1 peak distribution in patients from 35 to 39 years of age. The ratio of women to men was 1.2:1. Familial occurrence was 3.8%. The primary symptoms at initial presentation were intraventricular hemorrhage (42.0%), intracerebral hemorrhage (23.6%), intracerebral hemorrhage with intraventricular hemorrhage (18.3%), and subarachnoid hemorrhage (16.1%). Before the diagnosis, 68 patients experienced a second episode of bleeding. Rebleeding tends to be common within 6 years after the first bleeding (83.8%). The second bleeding episode was characterized by a change in which hemisphere bleeding occurred in 7 patients (10.3%) and by the type of bleeding in 23 patients (33.8%). Most patients presented with Suzuki stage 3 or 4 MMD (61.7%). Posterior cerebral artery involvement was observed in 28 (18.4%) patients. Forty-three intracranial aneurysms were identified in 39 patients (8.3%). CONCLUSIONS A 1-peak pattern in age distribution and mild female dominance in sex distribution were observed in patients with hemorrhagic MMD. Rebleeding tends to be common within 6 years after the first bleeding; however, some cases of rebleeding occur after a long period. Furthermore, the second bleeding episode was characterized frequently by a change in hemisphere and the type of bleeding. Early surgical treatment in both hemispheres is recommended.

Risk Factors for Epilepsy Recurrence after Revascularization in Pediatric Patients with Moyamoya Disease

OBJECTIVE We aimed to explore the risk factors of seizure recurrence and the optimal surgical procedure for epileptic pediatric patients with moyamoya disease (MMD). METHODS We reviewed 696 consecutive patients with MMD admitted to our hospital from 2009 to 2015. Pediatric patients with MMD who had seizures before revascularization were identified. We summarized the characteristics of seizures in pediatric patients with MMD and analyzed the predictive factors of recurrent seizure events. RESULTS We identified 28 pediatric patients with MMD who had seizures before revascularization. During follow-up (median 42 months), 7 patients (25.0%) experienced recurrent seizures. In the multivariate analysis, the duration of epilepsy was an independent predictor for postoperative seizure recurrences (odds ratio 3.84, 95% confidence interval 1.54-24.34; P = .035). The 2 common surgical modalities of MMD (direct and indirect bypass) had no significant difference in future seizure prevention in pediatric patients with MMD with epilepsy. CONCLUSIONS We identified the duration of epilepsy as an independent risk factor for recurrent seizure after revascularization in pediatric patients with MMD.

Steroid sulfatase and filaggrin mutations in a boy with severe ichthyosis, elevated serum IgE level and moyamoya syndrome

X-linked ichthyosis (XLI) is a relatively common, recessive condition caused by mutations in the steroid sulfatase (STS) gene. Common loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and predispose individuals to atopic eczema. We report a case of a 6-year-old boy who presented with unusually severe XLI, an increased serum immunoglobulin E level (2120IU/ml) and moyamoya angiopathy. Whole-exome sequencing identified a gross deletion encompassing the STS in Xp22.31 and the p.K4022X FLG mutation. The deletion is at least 1.6Mb in size in the proband, based on real-time quantitative polymerase chain reaction results. No other genetic mutations related to ichthyosis, moyamoya or hyper-immunoglobulin E syndrome were detected. Furthermore, his mothers brothers suffered from mild XLI and only had a deletion encompassing the STS. Additionally, his father and older sister suffered from mild ichthyosis vulgaris and had the p.K4022X FLG mutation. We report the first case of XLI with concurrent moyamoya syndrome. Moreover, an IgE-mediated immune response may have triggered the moyamoya signaling cascade in this patient with ichthyosis. Furthermore, our study strengthens the hypothesis that filaggrin defects can synergize with an STS deficiency to exacerbate the ichthyosis phenotype in an ethnically diverse population.

Association of Ring Finger Protein 213 Gene P.R4810k Polymorphism with Intracranial Major Artery Stenosis/Occlusion

BACKGROUND Intracranial major artery stenosis/occlusion (ICASO) is a common cause of ischemic stroke worldwide. A number of studies have assessed the association of the p.R4810K polymorphism in the ring finger protein 213 (RNF213) gene with ICASO, but the results have not been entirely consistent. METHODS We conducted a case-control study to estimate the association between the p.R4810K polymorphism and the risk of ICASO in a Chinese population. A total of 124 patients and 230 controls were enrolled. Moreover, a meta-analysis was performed to evaluate this association in the East Asian populations. RESULTS In our case-control study, the frequencies of the G/A genotype of p.R4810K were significantly higher in the ICASO patients than in the control group (4.03% versus .43%, P = .021, respectively). Moreover, in the meta-analysis, we assessed 7 case-control studies that included 1239 patients and 1377 controls. The pooled odds ratios (ORs) indicated significant association between the p.R4810K polymorphism and the ICASO risk in the dominant model (OR = 9.37, 95% confidence interval: 4.61-19.02, P = .000), the heterozygote comparison (OR = 8.97, 95% CI: 4.41-18.25, P = .000), and the allele comparison (OR = 9.50, 95% confidence interval: 4.71-19.19, P = .000) in the East Asian populations. Subgroup analysis based on ethnicity revealed that the risks in the Japanese and the Korean populations were higher than that in the Chinese population. CONCLUSIONS The p.R4810K polymorphism was associated with an increased risk of ICASO in the East Asian populations. Further studies on the function of the RNF213 protein and the clinical features of this subtype of ICASO are needed.