Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD.

BACKGROUND: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear. OBJECTIVE: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD. METHODS: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction. RESULTS: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009). CONCLUSIONS: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.

Postoperative cerebral infarction after revascularization in patients with moyamoya disease: Incidence and risk factors.

Objectives: Cerebral infarction is the major complication of revascularization surgery in patients with moyamoya disease (MMD), and we analyzed the possible causes of cerebral infarction after revascularization surgery for MMD. Methods: MMD patients who were admitted and underwent surgical revascularization at Shanghai Huashan Hospital from January 2019 to December 2021 were retrospectively analyzed. Results: A total of 815 patients and 890 revascularization surgeries (677 first revascularization surgeries and 213 second revascularization surgeries) were included in this study; 453 (50.9%) were performed on the left side and 437 (49.1%) on the right side, with 779 (87.5%) combined procedures and 111 (12.5%) indirect bypasses included. The mean patient age at the time of these procedures was 44.6 ± 11.7 years (range 6-72 years). Postoperative cerebral infarctions were observed in 46 (5.17%) surgeries, among which 31 occurred after left hemisphere revascularization surgeries, with an incidence of 6.84%, and 15 occurred after right hemisphere revascularization surgeries, with an incidence of 3.43%. Of these, 30 (65.2%) occurred in the operated hemispheres, 2 (4.3%) in the contralateral hemisphere and 13 (28.3%) in the bilateral hemisphere. There were 11 cases of massive infarction (23.9%). The incidence of postoperative infarction in patients undergoing the first revascularization was 6% (41/677) and 2.3% (5/213) in the second revascularization surgeries. Initial presentation as infarction (P < 0.001), initial presentation as hemorrhage (P < 0.001), hypertension (P = 0.018), diabetes (P = 0.006), 1st or 2nd surgery and surgical side (P = 0.007) were found to be related to postoperative cerebral infarction. Initial presentation as infarction (OR = 2.934, 95% CI 1.453-5.928, P = 0.003), initial presentation as hemorrhage (OR = 0.149, 95% CI 0.035-0.641, P = 0.011), and 1st or 2nd surgery and surgical side (OR = 1.66, 95% CI 1.106-2.491, P = 0.014) were independently associated with cerebral infarction after revascularization surgeries. Conclusions: In patients with MMD undergoing surgical revascularization, initial presentation as infarction and first revascularization surgery performed on the left hemisphere are independent risk factors for postoperative cerebral infarction, whereas initial presentation as hemorrhage is a protective factor.

Tracking mutant huntingtin aggregation kinetics in cells reveals three major populations that include an invariant oligomer pool.

Huntington disease is caused by expanded polyglutamine sequences in huntingtin, which procures its aggregation into intracellular inclusion bodies (IBs). Aggregate intermediates, such as soluble oligomers, are predicted to be toxic to cells, yet because of a lack of quantitative methods, the kinetics of aggregation in cells remains poorly understood. We used sedimentation velocity analysis to define and compare the heterogeneity and flux of purified huntingtin with huntingtin expressed in mammalian cells under non-denaturing conditions. Non-pathogenic huntingtin remained as hydrodynamically elongated monomers in vitro and in cells. Purified polyglutamine-expanded pathogenic huntingtin formed elongated monomers (2.4 S) that evolved into a heterogeneous aggregate population of increasing size over time (100-6,000 S). However, in cells, mutant huntingtin formed three major populations: monomers (2.3 S), oligomers (mode s(20,w) = 140 S) and IBs (mode s(20,w) = 320,000 S). Strikingly, the oligomers did not change in size heterogeneity or in their proportion of total huntingtin over 3 days despite continued monomer conversion to IBs, suggesting that oligomers are rate-limiting intermediates to IB formation. We also determined how a chaperone known to modulate huntingtin toxicity, Hsc70, influences in-cell huntingtin partitioning. Hsc70 decreased the pool of 140 S oligomers but increased the overall flux of monomers to IBs, suggesting that Hsc70 reduces toxicity by facilitating transfer of oligomers into IBs. Together, our data suggest that huntingtin aggregation is streamlined in cells and is consistent with the 140 S oligomers, which remain invariant over time, as a constant source of toxicity to cells irrespective of total load of insoluble aggregates.