Laterality of previous stoke affects endovascular thrombectomy outcomes.

BACKGROUND: Investigations into the effect of previous stroke on thrombectomy outcomes have yielded conflicting results, and are limited by small sample sizes. We present the results of a large single center retrospective study aimed at investigating the effect of chronic stroke laterality on thrombectomy outcomes. METHODS: A prospectively maintained database was queried for all thrombectomy cases conducted between December 2014 and January 2020, and patient imaging was prospectively reviewed for evidence of prior supratentorial infarction. Procedural, clinical, and demographic characteristics were recorded, and good clinical outcome was defined as a 90 day modified Rankin Scale (mRS) score of <2 or mRS score unchanged if baseline was >2. RESULTS: The final analysis cohort included 555 patients, 79 of whom were found to have radiographic evidence of prior chronic infarcts. On univariate analysis, patients with any chronic supratentorial infarct achieved a lower rate of good clinical outcome than patients with no chronic infarct (22.8% vs 41.0%, p=0.0021). With regard to subgroups, this difference remained only in patients with ipsilateral (14.3%, p=0.0018) and bilateral (11.8%, p=0.015) lesions. Patients with chronic contralateral supratentorial infarcts were no less likely to achieve good outcomes (40.7%, p=0.98). After multivariate regression controlling for age, sex, and baseline mRS, chronic ipsilateral infarcts (OR 0.22, CI 0.07 to 0.67) and chronic bilateral infarcts (OR 0.19, CI 0.04 to 0.85) were the only independent predictors of poor outcome in endovascular thrombectomy patients. CONCLUSIONS: In this single center retrospective study of thrombectomy patients with chronic supratentorial infarcts, the laterality of the previous stroke significantly affected the likelihood of good clinical outcomes.

Expression Changes in Mitochondrial Genes Affecting Mitochondrial Morphology, Transmembrane Potential, Fragmentation, Amyloidosis, and Neuronal Cell Death Found in Brains of Alzheimer's Disease Patients.

BACKGROUND: Alzheimer's disease (AD) is a neurological disease that has both a genetic and non-genetic origin. Mitochondrial dysfunction is a critical component in the pathogenesis of AD as deficits in oxidative capacity and energy production have been reported. OBJECTIVE: Nuclear-encoded mitochondrial genes were studied in order to understand the effects of mitochondrial expression changes on mitochondrial function in AD brains. These expression data were to be incorporated into a testable mathematical model for AD used to further assess the genes of interest as therapeutic targets for AD. METHODS: RT2-PCR arrays were used to assess expression of 84 genes involved in mitochondrial biogenesis in AD brains. A subset of mitochondrial genes of interest was identified after extensive Ingenuity Pathway Analysis (IPA) (Qiagen). Further filtering of this subset of genes of interest was achieved by individual qPCR analyses. Expression values from this group of genes were included in a mathematical model being developed to identify potential therapeutic targets. RESULTS: Nine genes involved in trafficking proteins to mitochondria, morphology of mitochondria, maintenance of mitochondrial transmembrane potential, fragmentation of mitochondria and mitochondrial dysfunction, amyloidosis, and neuronal cell death were identified as significant to the changes seen. These genes include TP53, SOD2, CDKN2A, MFN2, DNM1L, OPA1, FIS1, BNIP3, and GAPDH. CONCLUSION: Altered mitochondrial gene expression indicates that a subset of nuclear-encoded mitochondrial genes compromise multiple aspects of mitochondrial function in AD brains. A new mathematical modeling system may provide further insights into potential therapeutic targets.

Comparative study of intracranial access in thrombectomy using next generation 0.088 inch guide catheter technology.

BACKGROUND: Most conventional 0.088 inch guide catheters cannot safely navigate intracranial vasculature. The objective of this study is to evaluate the safety of stroke thrombectomy using a novel 0.088 inch guide catheter designed for intracranial navigation. METHODS: This is a multicenter retrospective study, which included patients over 18 years old who underwent thrombectomy for anterior circulation large vessel occlusions. Technical outcomes for patients treated using the TracStar Large Distal Platform (TracStar LDP) or earlier generation TRX LDP were compared with a matched cohort of patients treated with other commonly used guide catheters. The primary outcome measure was device-related complications. Secondary outcome measures included guide catheter failure and time between groin puncture and clot engagement. RESULTS: Each study arm included 45 patients. The TracStar group was non-inferior to the control group with regard to device-related complications (6.8% vs 8.9%), and the average time to clot engagement was 8.89 min shorter (14.29 vs 23.18 min; p=0.0017). There were no statistically significant differences with regard to other technical outcomes, including time to recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2B). The TracStar was successfully advanced into the intracranial internal carotid artery in 33 cases (73.33%); in three cases (6.67%), it was swapped for an alternate catheter. Successful reperfusion (mTICI 2B-3) was achieved in 95.56% of cases. Ninety-day follow-up data were available for 86.67% of patients, among whom 46.15% had an modified Rankin Score of 0-2%, and 10.26% were deceased. CONCLUSIONS: Tracstar LDP is safe for use during stroke thrombectomy and was associated with decreased time to clot engagement. Intracranial access was regularly achieved.

Early institutional experience using the TracStar Large Distal Platform in endovascular flow diversion.

INTRODUCTION: The delivery of flow-diverting stents (FDS) necessitates a degree of catheter support beyond that required for endovascular coiling. The TracStar Large Distal Platform (LDP) is a novel 0.088″ platform intended for navigation into the intracranial internal carotid artery (ICA). We present an early institutional experience using the TracStar LDP in 44 cases of endovascular aneurysm embolization using FDS. METHODS: Inclusion criteria for this single-center retrospective review encompassed all patients >18 years of age who were treated for intracranial aneurysms. Procedural success was defined as successful stent deployment using the TracStar LDP. Other outcomes included periprocedural complications, use of an intermediate catheter, length of stay, and discharge disposition. RESULTS: The TracStar LDP was utilized in 44 consecutive FDS cases in 42 patients. Cavernous segment aneurysms constituted the majority of cases (12/42; 28.6%), followed by posterior communicating artery (8/42; 19.0%) and supraclinoid aneurysms (8/42; 19.0%). Successful FDS deployment was achieved in 43/44 cases. The LDP achieved stable positioning within the ascending cavernous ICA in 63.6% of cases. A biaxial system was utilized in 54.5% of cases. There was one complication potentially related to use of the TracStar LDP, which was an asymptomatic ICA vessel dissection managed conservatively. CONCLUSIONS: The TracStar LDP is safe and effective during use in the endovascular treatment of intracranial aneurysms with a FDS. Access to the ascending portion of the cavernous ICA was regularly achieved, and the platform allowed for both biaxial and triaxial configurations.

Republished: First clinical report of aspiration through a novel 0.088-inch catheter positioned in the M1 middle cerebral artery for ELVO thrombectomy.

Two patients, separated by 1 year, underwent mechanical thrombectomy using next generation, highly navigable 0.088-inch large bore catheters, which were navigated to and aspirated within the M1 middle cerebral artery segment. Case 1 demonstrates the first reported clinical application of this technique used in conjunction with stent retriever and direct aspiration through an intermediate catheter, resulting in modified thrombolysis in cerebral infarction (mTICI) score 3 recanalisation, and a 90-day modified Rankin Score of 1. In case 2, direct on-clot aspiration was applied through a 0.088-inch guide catheter in the left M1 segment, resulting in mTICI score 3 recanalisation and a National Institutes of Health Stroke Scale score of 1 at discharge. There was no evidence of untoward events in either case. Advancement of a 0.088-inch catheter into the M1 segment offers potential benefits to thrombectomy by improving device-thrombus interaction, inducing local flow arrest and protecting proximal vessels from embolus to new territories.

First clinical report of aspiration through a novel 0.088-inch catheter positioned in the M1 middle cerebral artery for ELVO thrombectomy.

Two patients, separated by 1 year, underwent mechanical thrombectomy using next generation, highly navigable 0.088-inch large bore catheters, which were navigated to and aspirated within the M1 middle cerebral artery segment. Case 1 demonstrates the first reported clinical application of this technique used in conjunction with stent retriever and direct aspiration through an intermediate catheter, resulting in modified thrombolysis in cerebral infarction (mTICI) score 3 recanalisation, and a 90-day modified Rankin Score of 1. In case 2, direct on-clot aspiration was applied through a 0.088-inch guide catheter in the left M1 segment, resulting in mTICI score 3 recanalisation and a National Institutes of Health Stroke Scale score of 1 at discharge. There was no evidence of untoward events in either case. Advancement of a 0.088-inch catheter into the M1 segment offers potential benefits to thrombectomy by improving device-thrombus interaction, inducing local flow arrest and protecting proximal vessels from embolus to new territories.

The T9861C Mutation in the mtDNA-Encoded Cytochrome C Oxidase Subunit III Gene Occurs in High Frequency but with Unequal Distribution in the Alzheimer's Disease Brain.

Mitochondrial dysfunction is recognized as a critical component in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Deficits in oxidative capacity and, specifically, cytochrome c oxidase (CO) activity have been reported in AD brains and platelets. We previously identified a point mutation at np 9861 in AD brain mitochondrial DNA (mtDNA) that alters amino acid 219 of subunit III of CO from phenylalanine to leucine. We rapidly screened and quantitated levels of T9861C in samples using mismatched PCR-RFLP and nucleotide extension assays. Six of 40 AD brains possessed the T9861C mutation (designated AD+) compared to zero of 40 age-matched control brains. The 15% frequency of T9861C in AD brain is 115-fold higher than the frequency (0.13%) reported in 9,986 human mtDNA samples queried in world-wide databases. T9861C is heteroplasmic, with mutant load varying from 11% to >95%. Detected initially in parietal cortex, T9861C is not localized to that region but is also found in temporal cortex and caudate but not in hippocampus. The mutant load is unequally distributed throughout these brain regions with the highest load occurring in the parietal or temporal cortex. CO activity normalized to citrate synthase (CS) is reduced an average of 48.5% in AD+ brains. CO/CS ratios amongst controls and the two AD populations (AD and AD+) were significantly different (p = 0.001). Post hoc differences were also significant between controls and AD+ (p = 0.001) and controls and AD (p = 0.019). There was no significant difference between AD and AD+ (p = 0.317).