Person: Westover, Michael
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Westover
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Michael
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Westover, Michael
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Publication Physiological consequences of abnormal connectivity in a developmental epilepsy(Wiley-Blackwell, 2015) Shafi, Mouhsin; Vernet, Marine; Klooster, Debby; Chu, Catherine; Boric, Katica; Barnard, Mollie E.; Romatoski, Kelsey; Westover, Michael; Christodoulou, Joanna A.; Gabrieli, John D. E.; Whitfield-Gabrieli, Susan; Pascual-Leone, Alvaro; Chang, BernardObjective: Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. Methods: We employed transcranial magnetic stimulation (TMS) with simultaneous EEG recording in eight patients with epilepsy from periventricular nodular heterotopia (PNH) and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. Results: Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in one subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. Interpretation: Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions.Publication The standardization debate: A conflation trap in critical care electroencephalography(Elsevier BV, 2015) Ng, Marcus C.; Gaspard, Nicolas; Cole, Andrew; Hoch, Daniel; Cash, Sydney; Bianchi, Matt Travis; O’Rourke, Deirdre A.; Rosenthal, Eric; Chu, Catherine; Westover, MichaelPurpose: Persistent uncertainty over the clinical significance of various pathological continuous electroencephalography (cEEG) findings in the intensive care unit (ICU) has prompted efforts to standardize ICU cEEG terminology and an ensuing debate. We set out to understand the reasons for, and a satisfactory resolution to, this debate. Method: We review the positions for and against standardization, and examine their deeper philosophical basis. Results: We find that the positions for and against standardization are not fundamentally irreconcilable. Rather, both positions stem from conflating the three cardinal steps in the classic approach to EEG, which we term “description”, “interpretation”, and “prescription”. Using real-world examples we show how this conflation yields muddled clinical reasoning and unproductive debate among electroencephalographers that is translated into confusion among treating clinicians. We propose a middle way that judiciously uses both standardized terminology and clinical reasoning to disentangle these critical steps and apply them in proper sequence. Conclusion: The systematic approach to ICU cEEG findings presented herein not only resolves the standardization debate but also clarifies clinical reasoning by helping electroencephalographers assign appropriate weights to cEEG findings in the face of uncertainty.Publication The probability of seizures during EEG monitoring in critically ill adults(Elsevier BV, 2015) Westover, Michael; Shafi, Mouhsin; Bianchi, Matt Travis; Moura, Lidia M.V.R.; O’Rourke, Deirdre; Rosenthal, Eric; Chu, Catherine; Donovan, Samantha; Hoch, Daniel; Kilbride, Ronan D.; Cole, Andrew; Cash, SydneyObjective: To characterize the risk for seizures over time in relation to EEG findings in hospitalized adults undergoing continuous EEG monitoring (cEEG). Methods: Retrospective analysis of cEEG data and medical records from 625 consecutive adult inpatients monitored at a tertiary medical center. Using survival analysis methods, we estimated the time-dependent probability that a seizure will occur within the next 72-h, if no seizure has occurred yet, as a function of EEG abnormalities detected so far. Results: Seizures occurred in 27% (168/625). The first seizure occurred early (<30 min of monitoring) in 58% (98/168). In 527 patients without early seizures, 159 (30%) had early epileptiform abnormalities, versus 368 (70%) without. Seizures were eventually detected in 25% of patients with early epileptiform discharges, versus 8% without early discharges. The 72-h risk of seizures declined below 5% if no epileptiform abnormalities were present in the first two hours, whereas 16 h of monitoring were required when epileptiform discharges were present. 20% (74/388) of patients without early epileptiform abnormalities later developed them; 23% (17/74) of these ultimately had seizures. Only 4% (12/294) experienced a seizure without preceding epileptiform abnormalities. Conclusions: Seizure risk in acute neurological illness decays rapidly, at a rate dependent on abnormalities detected early during monitoring. This study demonstrates that substantial risk stratification is possible based on early EEG abnormalities. Significance: These findings have implications for patient-specific determination of the required duration of cEEG monitoring in hospitalized patients.Publication Emergence of Stable Functional Networks in Long-Term Human Electroencephalography(Society for Neuroscience, 2012) Chu, Catherine; Kramer, Mark; Pathmanathan, Jay Sriram; Bianchi, Matt Travis; Westover, Michael; Wizon, L.; Cash, SydneyFunctional connectivity networks have become a central focus in neuroscience because they reveal key higher-dimensional features of normal and abnormal nervous system physiology. Functional networks reflect activity-based coupling between brain regions that may be constrained by relatively static anatomical connections, yet these networks appear to support tremendously dynamic behaviors. Within this growing field, the stability and temporal characteristics of functional connectivity brain networks have not been well characterized. We evaluated the temporal stability of spontaneous functional connectivity networks derived from multi-day scalp encephalogram (EEG) recordings in five healthy human subjects. Topological stability and graph characteristics of networks derived from averaged data epochs ranging from 1 s to multiple hours across different states of consciousness were compared. We show that, although functional networks are highly variable on the order of seconds, stable network templates emerge after as little as ∼100 s of recording and persist across different states and frequency bands (albeit with slightly different characteristics in different states and frequencies). Within these network templates, the most common edges are markedly consistent, constituting a network “core.” Although average network topologies persist across time, measures of global network connectivity, density and clustering coefficient, are state and frequency specific, with sparsest but most highly clustered networks seen during sleep and in the gamma frequency band. These findings support the notion that a core functional organization underlies spontaneous cortical processing and may provide a reference template on which unstable, transient, and rapidly adaptive long-range assemblies are overlaid in a frequency-dependent manner.Publication Should a Sentinel Node Biopsy Be Performed in Patients with High-Risk Breast Cancer?(SAGE-Hindawi Access to Research, 2011) Westover, Kenneth Dale; Westover, Michael; Winer, Eric; Richardson, Andrea; Iglehart, James; Punglia, RinaaA negative sentinel lymph node (SLN) biopsy spares many breast cancer patients the complications associated with lymph node irradiation or additional surgery. However, patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably high risk of axillary disease even after a negative SLN biopsy result. A Bayesian nomogram was designed to combine the probability of axillary disease prior to nodal biopsy with customized test characteristics for an SLN biopsy and provides the probability of axillary disease despite a negative SLN biopsy. Users may individualize the sensitivity of an SLN biopsy based on factors known to modify the sensitivity of the procedure. This tool may be useful in identifying patients who should have expanded upfront exploration of the axilla or comprehensive axillary irradiation.Publication Significance Testing as Perverse Probabilistic Reasoning(BioMed Central, 2011) Westover, Michael; Westover, Kenneth Dale; Bianchi, Matt TravisTruth claims in the medical literature rely heavily on statistical significance testing. Unfortunately, most physicians misunderstand the underlying probabilistic logic of significance tests and consequently often misinterpret their results. This near-universal misunderstanding is highlighted by means of a simple quiz which we administered to 246 physicians at two major academic hospitals, on which the proportion of incorrect responses exceeded 90%. A solid understanding of the fundamental concepts of probability theory is becoming essential to the rational interpretation of medical information. This essay provides a technically sound review of these concepts that is accessible to a medical audience. We also briefly review the debate in the cognitive sciences regarding physicians' aptitude for probabilistic inference.Publication Seizure Prophylaxis After Spontaneous Intracerebral Hemorrhage(American Medical Association (AMA), 2021-09-01) Simoes Jones, Felipe Jorge; Sanches, Paula; Smith, Jason; Zafar, Sahar; Blacker, Deborah; Hsu, John; Schwamm, Lee; Newhouse, Joseph; Westover, Michael; Moura, Lidia MariaImportance: There is limited evidence concerning optimal seizure prophylaxis after spontaneous intracerebral hemorrhage (sICH). Objective: To evaluate which of four seizure prophylaxis strategies provides the greatest net benefit for sICH patients. Design, Setting, and Participants: Decision model simulating four common scenarios: 1) 60-year-old male with low early- (≤ 7 days post-stroke) (10%) and late-seizure risks (3.6% or 9.8%), and average short- and long-term adverse drug reaction (ADR) risks (9% and 30%, respectively); 2) 80-year-old female with low early- (10%) and late-seizure risks (3.6% or 9.8%), and high short- and long-term ADR risks (24% and 80%); 3) 55-year-old male with high early- (19%) and late-seizure risks (34.8% or 46.2%), and low short- and long-term ADR risks (9% and 30%); and 4) 45-year-old female with high early- (19%) and late-seizure risks (34.8% or 46.2%), and high short- and long-term ADR risks (18% and 60%). Interventions: Four antiseizure drug strategies: 1) Conservative: short-term (7-day) secondary early-seizure prophylaxis with long-term therapy after late-seizure; 2) Moderate: long-term secondary early- or late-seizure prophylaxis; 3) Aggressive: long-term primary prophylaxis; 4) Risk-guided: short-term secondary early-seizure prophylaxis among low-risk patients (2HELPS2B score), short-term primary prophylaxis among higher-risk patients, and long-term late-seizure secondary therapy. Main Outcomes and Measures: Quality-adjusted life years (QALYs). Results: For scenario 1, risk-guided strategy was preferred over conservative, moderate, and aggressive (QALYs = 8.13, 8.08, 8.07, and 7.88, respectively). For scenario 2, conservative and risk-guided strategies performed comparably and were favored over moderate and aggressive (QALYs = 2.18, 2.17, 2.09, 1.15). For scenario 3, aggressive strategy was preferred over moderate, risk-guided and conservative (QALY = 9.21, 8.93, 8.98, 8.77). For scenario 4, risk-guided strategy was preferred over conservative, moderate, and aggressive (QALY = 11.53, 11.23, 10.93, 8.08). Sensitivity analyses suggested that short-term strategies are preferred under most scenarios, and the risk-guided strategy performs comparably or better than alternative strategies in most settings. Conclusions and Relevance: Our model indicates that short-term (7-day) prophylaxis dominates longer-term therapy following sICH. Implementation of the 2HELPS2B score to guide clinical decisions for initiation of short-term primary versus secondary early-seizure prophylaxis should be considered for all patients after sICH.