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1. Standardized Brain MRI Acquisition Protocols Improve Statistical Power in Multicenter Quantitative Morphometry Studies

Author

George, A, Kuzniecky, R, Rusinek, H, Pardoe, HR, French, J, Lowenstein, D, Cristofaro, S, McKenna, K, Mays, V, Shack, D, Barnard, S, Burke, C, Hegde, M, Glauser, T, O'Brien, T, Pollard, J, Ting, T, Meador, K, Darby, D, Morrison, C, Penovich, P, Schembri, A, Kanner, A, Altilab, HH, Barry, J, Hesdorffer, D, Hope, O, Nadkarni, S, Sperling, M, Winawer, M, Dlugos, D, Beal, J, Boro, A, Herman, S, Singh, R, Halford, J, Thio, LL, Pardoe, H, Cascino, G, Glynn, S, Jackson, G, Knowlton, R, Gidal, B, Abou-Khalil, B, Alldredge, B, Faught, E, Ficker, D, Klein, P, Mintzer, S, Detyniecki, K, Haut, S, Hixson, J, Holmes, M, Kalviainen, R, Widdess-Walsh, P, Krishnamurthy, K, Park, K, Gelfand, M, Kang, J, Krauss, G, Cole, A, Atkinson, P, Trinka, E, Kirschner, M, Schmid, E, Somerville, E, Zentner, C, Laue-Gizzi, H, Rodriguez, A, Devinsky, O, Nadkarni, M, Cook, M, Berkovic, S, Bebin, M, Szaflarsk, J, Szabo, C, Burneo, J, Abou-Khalil, BW, Weisenberg, J, Altilab, H, George, A, Kuzniecky, R, Rusinek, H, Pardoe, HR, French, J, Lowenstein, D, Cristofaro, S, McKenna, K, Mays, V, Shack, D, Barnard, S, Burke, C, Hegde, M, Glauser, T, O'Brien, T, Pollard, J, Ting, T, Meador, K, Darby, D, Morrison, C, Penovich, P, Schembri, A, Kanner, A, Altilab, HH, Barry, J, Hesdorffer, D, Hope, O, Nadkarni, S, Sperling, M, Winawer, M, Dlugos, D, Beal, J, Boro, A, Herman, S, Singh, R, Halford, J, Thio, LL, Pardoe, H, Cascino, G, Glynn, S, Jackson, G, Knowlton, R, Gidal, B, Abou-Khalil, B, Alldredge, B, Faught, E, Ficker, D, Klein, P, Mintzer, S, Detyniecki, K, Haut, S, Hixson, J, Holmes, M, Kalviainen, R, Widdess-Walsh, P, Krishnamurthy, K, Park, K, Gelfand, M, Kang, J, Krauss, G, Cole, A, Atkinson, P, Trinka, E, Kirschner, M, Schmid, E, Somerville, E, Zentner, C, Laue-Gizzi, H, Rodriguez, A, Devinsky, O, Nadkarni, M, Cook, M, Berkovic, S, Bebin, M, Szaflarsk, J, Szabo, C, Burneo, J, Abou-Khalil, BW, Weisenberg, J, and Altilab, H

Abstract

BACKGROUND AND PURPOSE: In this study, we used power analysis to calculate required sample sizes to detect group-level changes in quantitative neuroanatomical estimates derived from MRI scans obtained from multiple imaging centers. Sample size estimates were derived from (i) standardized 3T image acquisition protocols and (ii) nonstandardized clinically acquired images obtained at both 1.5 and 3T as part of the multicenter Human Epilepsy Project. Sample size estimates were compared to assess the benefit of standardizing acquisition protocols. METHODS: Cortical thickness, hippocampal volume, and whole brain volume were estimated from whole brain T1-weighted MRI scans processed using Freesurfer v6.0. Sample sizes required to detect a range of effect sizes were calculated using (i) standard t-test based power analysis methods and (ii) a nonparametric bootstrap approach. RESULTS: A total of 32 participants were included in our analyses, aged 29.9 ± 12.62 years. Standard deviation estimates were lower for all quantitative neuroanatomical metrics when assessed using standardized protocols. Required sample sizes per group to detect a given effect size were markedly reduced when using standardized protocols, particularly for cortical thickness changes <.2 mm and hippocampal volume changes <10%. CONCLUSIONS: The use of standardized protocols yielded up to a five-fold reduction in required sample sizes to detect disease-related neuroanatomical changes, and is particularly beneficial for detecting subtle effects. Standardizing image acquisition protocols across scanners prior to commencing a study is a valuable approach to increase the statistical power of multicenter MRI studies.

Published
2019

4. Clinical and electrographic features of persistent seizures and status epilepticus associated with anti-NMDA receptor encephalitis (anti-NMDARE).

Author

Gofshteyn JS, Yeshokumar AK, Jette N, Thakur KT, Luche N, Yozawitz E, Varnado S, Klenofsky B, Tuohy MC, Ankam J, Torres S, Hesdorffer D, Nelson A, Wolf S, McGoldrick P, Yan H, Basma N, and Grinspan Z

Subjects
Adolescent, Adult, Age Factors, Anti-N-Methyl-D-Aspartate Receptor Encephalitis complications, Anticonvulsants administration & dosage, Child, Child, Preschool, Databases, Factual, Drug Resistant Epilepsy drug therapy, Drug Resistant Epilepsy etiology, Drug Resistant Epilepsy physiopathology, Epilepsies, Partial drug therapy, Epilepsies, Partial etiology, Epilepsies, Partial physiopathology, Epilepsy drug therapy, Epilepsy etiology, Frontal Lobe physiopathology, Humans, Retrospective Studies, Status Epilepticus drug therapy, Status Epilepticus etiology, Young Adult, Anti-N-Methyl-D-Aspartate Receptor Encephalitis physiopathology, Electroencephalography, Epilepsy physiopathology, Status Epilepticus physiopathology
Abstract

Based on a multicenter cohort of people with anti-NMDA receptor encephalitis (anti-NMDARE), we describe seizure phenotypes, electroencephalographic (EEG) findings, and anti-seizure treatment strategies. We also investigated whether specific electrographic features are associated with persistent seizures or status epilepticus after acute presentation. In this retrospective cohort study, we reviewed records of children and adults with anti-NMDARE between 2010 and 2014 who were included in the Rare Epilepsy of New York City database, which included the text of physician notes from five academic medical centers. Clinical history (e.g., seizure semiology) and EEG features (e.g., background organization, slowing, epileptiform activity, seizures, sleep architecture, extreme delta brush) were abstracted. We compared clinical features associated with persistent seizures (ongoing seizures after one month from presentation) and status epilepticus, using bivariate and multivariable analyses. Among the 38 individuals with definite anti-NMDARE, 32 (84%) had seizures and 29 (76%) had seizures captured on EEG. Electrographic-only seizures were identified in five (13%) individuals. Seizures started at a median of four days after initial symptoms (IQR: 3-6 days). Frontal lobe-onset focal seizures were most common (n=12; 32%). Most individuals (31/38; 82%) were refractory to anti-seizure medications. Status epilepticus was associated with younger age (15 years [9-20] vs. 23 years [18-27]; p=0.04) and Hispanic ethnicity (30 [80%] vs. 8 [36%]; p=0.04). Persistent seizures (ongoing seizures after one month from presentation) were associated with younger age (nine years [3-14] vs. 22 years [15-28]; p<0.01). Measured electrographic features were not associated with persistent seizures. Seizures associated with anti-NMDARE are primarily focal seizures originating in the frontal lobes. Younger patients may be at increased risk of epileptogenesis and status epilepticus. Continuous EEG monitoring helps identify subclinical seizures, but specific EEG findings may not predict the severity or persistence of seizures during hospitalization.

Published
2020
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