Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations.

Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

Intraoperative direct venous puncture and embolization for arteriovenous shunt below the conus medullaris: a prospective cohort study.

BACKGROUND: Arteriovenous shunt below the conus medullaris (AVS-BC) is easily misdiagnosed and mistreated due to its rarity. Achieving an anatomical cure solely through endovascular or surgical means is challenging. This study aimed to summarize the clinical and radiological features of AVS-BC and evaluate the safety and efficacy of hybrid techniques represented by intraoperative direct venous puncture and embolization (IVPE). METHODS: The patients with AVS-BC were grouped into those with dural, intradural, and paravertebral shunts. The patients undergoing hybrid procedures were consecutively recruited between August 2016 and July 2022. The modified Aminoff and Logue's Scale (mALS) and the modified Denis Pain and Numbness Scale (mDS) were used to evaluate motor and sensation disturbances. RESULTS: A total of 42 patients (35 males, 83.3%) were included with an average age of 57.38±10.79 years. Most patients presented with lower limb weakness and sphincter disturbances. Their preoperative average mALS score was 7.17±2.61 and the preoperative average mDS score was 3.88±1.76. There were 28 patients (66.7%) who received IVPE. The mean clinical follow-up reached 41.30±21.10 months. All patients achieved anatomical cures without permanent neurological complications. It showed a significant improvement in mALS scores after the intervention in the spinal dural arteriovenous fistula only (P=0.026). No recurrences were reported. CONCLUSIONS: Differentiating AVS-BC mainly relied on identifying supplying arteries, shunt placements, and draining veins. The hybrid technique typified by IVPE conferred a safe anatomical cure for AVS-BC.

Plasma Phosphorylated Tau181 and Amyloid-ß42 in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People.

BACKGROUND: Increasing evidence illustrates the value of plasma biomarkers of Alzheimer's disease (AD) to screen for and identify dementia with Lewy bodies (DLB). However, confirmatory studies are needed to demonstrate the feasibility of these markers. OBJECTIVE: To determine the feasibility of plasma tau phosphorylated at threonine 181 (p-tau181) and amyloid-ß42 (Aß42) as potential biomarkers to differentiate AD and DLB. METHODS: We evaluated plasma samples from patients with DLB (n = 47) and AD (n = 55) and healthy controls (HCs, n = 30), using ELISAs to measure p-tau181 and Aß42. Additionally, we examined neuropsychological assessment scores for participants. The plasma biomarkers were investigated for correlation with neuropsychological assessments and discriminant ability to identify DLB. RESULTS: Plasma p-tau181 was significantly lower in DLB than in AD and HCs. Plasma Aß42 was significantly higher in DLB than in AD but lower in DLB than in HCs. We found good correlations between plasma Aß42 and neuropsychological scores in the whole cohort, while p-tau181 was associated with cognitive status in DLB. In the distinction between DLB and HCs, plasma p-tau181 and Aß42 showed similar accuracy, while Aß42 showed better accuracy than p-tau181 in discriminating DLB and AD. CONCLUSION: In a single-center clinical cohort, we confirmed the high diagnostic value of plasma p-tau181 and Aß42 for distinguishing patients with DLB from HCs. Plasma Aß42 improved the differential diagnosis of DLB from AD.

A retrospective study of 78 adult tentorial middle line region dural arteriovenous fistulae.

OBJECTIVE: Dural arteriovenous fistulae (DAVF) in the tentorial middle line region are uncommon with specific features and more cognitive disorders than any other region. The purpose of this study is to present clinical characteristics and our experience with endovascular treatment in this specific region. METHODS: During a 20-year period, 94.9% of patients (74/78) underwent endovascular treatment (36 in galenic, 48.6%) (12 in straight sinus, 16.2%) (26 in torcular, 35.1%). There were 63 males and 15 females with mean age of 50 (50 ± 12) years in total of 78 patients. The clinical presentation, angiographic features, treatment strategy, and clinical outcomes were recorded. RESULTS: Transarterial embolization (TAE) was performed in 89.2% of the 74 patients (66/74), transvenous embolization alone in one patient and mixed approach in seven. Complete obliteration of the fistulas was obtained in 87.5% of the patients (64/74). 71 patients (mean, 56 months) had phone, outpatient, or admission follow-up. The digital subtraction angiography (DSA) follow-up period (25/78, 32.1%) was 13.8 (6-21) months. Two of them (2/25, 8%) had fistula recurrences after complete embolization and were embolized again. The phone follow-up period (70/78, 89.7%) was 76.6 (40-92.3) months. Pre-embolization and post-embolization mRS ≥ 2 were in 44 patients (44/78) and 15 (15/71) patients, respectively. DAVF with internal cerebral vein drainage (OR 6.514, 95% Cl 1.201-35.317) and intracranial hemorrhage (OR 17.034, 95% Cl 1.122-258.612) during TAE were the risk factors for predicting poor outcomes (followed up mRS ≥ 2). CONCLUSIONS: TAE is the first-line treatment for tentorial middle line region DAVF. When pial feeders' obliteration is difficult to achieve, it should not be forced due to the poor outcomes after intracranial hemorrhage. The cognitive disorders caused by this region were not reversible as reported. It is imperative to enhance the care provided to these patients with cognitive disorders.

Acanthocytes Identified in Huntington's Disease.

Background: Neuroacanthocytosis (NA) and Huntington's disease (HD) are neurodegenerative conditions that share clinical symptoms and imaging findings, despite their distinct genetic etiologies. Usually, the presence of acanthocytes can help narrow the differential diagnosis of a familial choreiform disorder, as the diagnosis of NA syndrome is supported by the presence of acanthocytes in peripheral blood. In this study, we demonstrate four patients who present with HD and acanthocytosis. Methods: We retrieved the data of 40 HD patients with fresh peripheral blood screened for erythrocytes in our hospital from 2014 to 2022. Of these 40 patients, four patients with acanthocytes were recruited for this study. Patients' investigations included clinical and laboratory studies, HTT gene sequencing, and whole-exome sequencing. Fresh peripheral blood was screened for erythrocytes by scanning electron microscopy. Results: The four adult patients were Han Chinese and unrelated. The age ranged from 45 to 61 years, with a disease duration of 4-10 years. The main neurological features at diagnosis included progressive involuntary movements, psychiatric changes, and dementia. Genetic analysis showed an expansion at the HTT gene. The mean proportion of acanthocytes was mild (6-10%) elevated in patient one and high (>20%) elevated in patients 2-4 by scanning electron microscopy examination. Conclusion: Our study illustrates that HD can combine with acanthocytosis, which may expand the clinical phenotype. Even though the primary gene defect appears to be predominately directed at the brain, a peripheral defect can be seen in HD. Our study highlights the complexity and diversity of HD.