OBJECTIVE Cerebral extracranial-intracranial (EC-IC) direct bypass is a commonly used procedure for ischemic vasculopathy. A previously described variation of this technique is to utilize one donor artery to supply two recipient arteries, which the authors designate as 1D2R. The purpose of this study is to present a single surgeon’s series of 1D2R direct bypasses for moyamoya and ischemia using detailed clinical, angiographic, and intraoperative blood flow measurement data. To the authors’ knowledge, this is the largest series reported to date. METHODS Hospital, office, and radiographic imaging records for all patients who underwent cerebral revascularization using a 1D2R bypass by the senior author were reviewed. The patients’ demographic information, clinical presentation, associated medical conditions, intraoperative information, and postoperative course were obtained from reviewing the medical records. RESULTS A total of 21 1D2R bypasses were performed in 19 patients during the study period. Immediate bypass patency was 100% and was 90% on delayed follow-up. The mean initial cut flow index (CFI(i)) was 0.64 ± 0.33 prior to the second anastomosis and the mean final value (CFI(f)) was 0.94 ± 0.38 after the second anastomosis (p < 0.001). The overall bypass flow increased on average by 50% (mean 17.9 ml/min, range −10 to 40 ml/min) with the addition of the second anastomosis. There was no significant difference in the overall flow measurements when the end-to-side anastomosis or side-to-side anastomosis was performed first. There was a statistically significant difference in the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 postoperatively compared to preoperatively (p < 0.01). Through the application of Poiseuille’s law, the authors analyzed flow dynamics, deduced the component vascular resistances based on an analogy to electrical circuits and Ohm’s law, and introduced the new concepts of “second anastomosis relative augmentation” and “second anastomosis sink index” in the evaluation of 1D2R bypasses. CONCLUSIONS The application of the 1D2R technique in a series of 19 consecutive patients undergoing direct EC-IC bypass for flow augmentation demonstrated high patency rates, statistically significantly higher CFIs compared to 1D1R, and improved mRS scores at last clinical follow-up. Additionally, the technique allows a shorter dissection time and preserves blood flow to the scalp. The routine utilization of intraoperative volumetric flow measurements in such surgeries allows a deeper understanding of the hemodynamic impact on individual patients.
Over 15 million epilepsy patients worldwide have drug-resistant epilepsy. Successful surgery is a standard of care treatment but can only be achieved through complete resection or disconnection of the epileptogenic zone, the brain region(s) where seizures originate. Surgical success rates vary between 20% and 80%, because no clinically validated biological markers of the epileptogenic zone exist. Localizing the epileptogenic zone is a costly and time-consuming process, which often requires days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity on individual channels occurring immediately before seizures or spikes that occur interictally (i.e. between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in epileptogenic zone localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. IEEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aimed to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the epileptogenic zone. We hypothesized that when a patient is not clinically seizing, it is because the epileptogenic zone is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighbouring nodes (‘sources’) and the inhibited nodes themselves (‘sinks’). Specifically, patient-specific dynamical network models were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics. We validated the algorithm in a retrospective analysis of 65 patients. The source-sink metrics identified epileptogenic regions with 73% accuracy and clinicians agreed with the algorithm in 93% of seizure-free patients. The algorithm was further validated by using the metrics of the annotated epileptogenic zone to predict surgical outcomes. The source-sink metrics predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians’ predictions (surgical success rate of this dataset). In failed outcomes, we identified brain regions with high metrics that were untreated. When compared with high frequency oscillations, the most commonly proposed interictal iEEG feature for epileptogenic zone localization, source-sink metrics outperformed in predictive power (by a factor of 1.2), suggesting they may be an interictal iEEG fingerprint of the epileptogenic zone.
Over 15 million epilepsy patients worldwide have medically refractory epilepsy (MRE), i.e., they do not respond to anti-epileptic drugs. Successful surgery is a hopeful alternative for seizure freedom but can only be achieved through complete resection or disconnection of the epileptogenic zone (EZ), the brain region(s) where seizures originate. Unfortunately, surgical success rates vary between 30%-70% because no clinically validated biological markers of the EZ exist. Localizing the EZ has thus become a costly and time-consuming process during which a team of clinicians obtain non-invasive neuroimaging data, which is often followed by invasive monitoring involving days-to-weeks of EEG recordings captured intracranially (iEEG). Clinicians visually inspect iEEG data, looking for abnormal activity (e.g., low-voltage high frequency activity) on individual channels occurring immediately before seizures. They also look for abnormal spikes that occur on iEEG between seizures ("resting-state"). In the end, clinicians use <1% of the iEEG data captured to assist in EZ localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored data to better diagnose and treat patients. Intracranial EEG offers a unique opportunity to observe rich epileptic cortical network dynamics but waiting for seizures to occur increases patient risks associated invasive monitoring. In this study, we aim to leverage iEEG data in between seizures by developing a new networked-based resting-state iEEG marker of the EZ. We hypothesize that when a patient is not seizing, it is because the EZ is inhibited by neighboring nodes. We develop an algorithm that identifies two groups of nodes from the resting-state iEEG network: those that are continuously inhibiting a set of neighboring nodes ("sources") and the inhibited nodes themselves ("sinks"). Specifically, patient-specific dynamical network models (DNMs) are estimated from minutes of iEEG and their connectivity properties reveal top sources and sinks in the network, with each node being quantified by a source-sink index (SSI). We validate the SSI index in a retrospective analysis of 65 patients by using the SSI of the annotated EZ as a metric to predict surgical outcomes. SSI predicts with an accuracy of 79%, compared to the accuracy of clinicians being 43% (successful outcomes). In failed outcomes, we identify regions of the brain with high SSIs that were untreated. When compared to high frequency oscillations, the most common resting-state iEEG feature proposed for EZ localization, SSI outperformed in predictive power (by a factor of 1.2) suggesting SSI as a resting-state EEG fingerprint of the EZ.
BACKGROUND: Moyamoya disease is a chronic, progressive cerebrovascular disease involving occlusion or stenosis of the terminal portion of the internal carotid artery. We conducted an updated systematic review and meta-analysis to investigate clinical and angiographic outcomes comparing direct, combined, and indirect bypass for the treatment of moyamoya disease in adults. METHODS: Two independent authors performed Preferred Reporting Items for Systematic reviews and Meta-Analyses guided literature searches in December 2021 to identify articles reporting clinical/angiographic outcomes in adult moyamoya disease patients undergoing bypass. Primary end points used were ischemic and hemorrhagic strokes, clinical outcomes, and angiographic revascularization. Study quality was evaluated with Newcastle-Ottawa and the Oxford Center for Evidence-Based Medicine scales. RESULTS: Four thousand four hundred fifty seven articles were identified in the initial search; 143 articles were analyzed. There were 3827 direct, 3826 indirect, and 3801 combined bypasses. Average length of follow-up was 3.59±2.93 years. Pooled analysis significantly favored direct (odds ratio [OR], 0.62 [0.48–0.79]; P <0.0001; OR, 0.44 [0.32–0.59]; P <0.0001; OR, 0.56 [0.42–0.74]; P <0.0001; OR, 3.1 [2.5–3.8]; P =0.0001) and combined (OR, 0.53 [0.41–0.69]; P <0.0001; OR, 0.28 [0.2–0.41]; P <0.0001; OR, 0.41 [0.3–0.56]; P <0.0001; OR, 3.1 [2.8–4.3]; P =0.0001) over indirect bypass for early stroke, late stroke, late intracerebral hemorrhage, and favorable outcomes, respectively. Indirect bypass was favored over combined (OR, 3.1 [1.7–5.6]; P <0.0001) and direct (OR, 4.12 [2.34–7.25]; P <0.0001) for early intracerebral hemorrhage. The meta-analysis significantly favored direct (OR, 0.37 [0.23–0.60]; P <0.001; OR, 0.49 [0.31–0.77]; P =0.002) and combined (OR, 0.23 [0.12–0.43]; P <0.00001; OR, 0.30 [0.18–0.49]; P <0.00001) bypass over indirect bypass for late stroke and late hemorrhage, respectively. Combined bypass was favored over indirect bypass for favorable outcomes (OR, 2.06 [1.18–3.58]; P =0.01). CONCLUSIONS: Based on combined meta-analysis (43 articles) and pooled analysis (143 articles), the existing literature indicates that combined and direct bypasses have significant benefits for patients suffering from late stroke and hemorrhage versus indirect bypass. Combined bypass was favored over indirect bypass for favorable outcomes. This is a strong recommendation based on low-quality evidence when utilizing the Grades of Recommendation, Assessment, Development, and Evaluation system. These findings have important implications for bypass strategy selection.
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