Jacqueline A. French
Temple University
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Annals of Neurology | 2015
Robert Wechsler; Robert A. Hauser; Jacqueline A. French; Carl W. Bazil; Elinor Ben-Menachem; Gregory D. Cascino; Dennis J. Dlugos; Edward Faught; Hubert H. Fernandez; Evan Fertig; Jonathan J. Halford; Cynthia L. Harden; Jay Harvey; Allen Hauser; Sheryl R. Haut; Susan T. Herman; Lawrence J. Hirsch; R. Edward Hogan; Andres M. Kanner; Peter W. Kaplan; Pavel Klein; Daniel Kremens; Allan Krumholz; Mark F. Lew; Kimford J. Meador; Scott Mintzer; Rajesh Pahwa; Patricia Penovich; John R. Pollard; Jerry J. Shih
We thank Thom and colleagues for their letter addressing human papilloma virus (HPV) in focal cortical dysplasia (FCD) and other epilepsy-associated brain pathologies. They suggest that what was previously reported as the HPV E6 oncoprotein in FCDIIB is “a cross-reaction with an as-yet unidentified neuroglial protein.” We appreciate their findings, because validation or refutation of the previous findings of HPV in FCD and glioblastoma has important public health relevance. However, several issues limit the conclusions of Thom et al, including a very small sample size, a limited description of experimental methods, incomplete experimental approaches to validate their claims, and most importantly, a failure to identify the proposed neuroglial protein. Furthermore, their report does not adequately explain the detection of the HPV viral capsid protein L1 in FCD. If the E6 oncoprotein detection is artifactual or nonpathogenic, then L1 should not be detected, because L1 and E6 are entirely nonhomologous proteins encoded by distinct genes in the HPV genome. It is puzzling that both L1 and E6 would be expressed in FCD as experimental artifact. The theory that an in utero viral infection plays a pathogenic role in brain malformations is not new and there is evidence, for example, that cytomegalovirus can cause pachygyria and smaller focal malformations. As we stated previously, the detection of E6 suggests an association between HPV and FCD but does not prove HPV pathogenicity in FCD, and further comprehensive studies are warranted to critically assess existing data sets. Until adequately powered studies are published, we stand by our original report.
Neurology: Clinical Practice | 2018
David Neal Franz; John A. Lawson; Zuhal Yapici; Hiroko Ikeda; Tilman Polster; Rima Nabbout; Paolo Curatolo; Petrus J. de Vries; Dennis J. Dlugos; Maurizio Voi; Jenna Fan; Alexandra Vaury; Diana Pelov; Jacqueline A. French
Background EXamining everolimus In a Study of Tuberous sclerosis 3 (EXIST-3) demonstrated significantly reduced seizure frequency (SF) with everolimus vs placebo. In this study, we evaluate the long-term efficacy and safety of everolimus for tuberous sclerosis complex (TSC)-associated treatment-refractory seizures. Methods After completion of the core phase, patients could enter an open-label extension phase and receive everolimus (target exposure, 3–15 ng/mL) for ≥48 weeks. Efficacy end points included change from baseline in average weekly SF expressed as response rate (RR, ≥50% reduction) and median percentage reduction (PR). Results Of 366 patients, 361 received everolimus in core/extension phases. The RR was 31% (95% CI, 26.2–36.1; N = 352) at week 18, 46.6% (95% CI, 40.9–52.5; N = 298) at 1 year, and 57.7% (95% CI, 49.7–65.4; N = 163) at 2 years. Median PR in SF was 31.7% (95% CI, 28.5–36.1) at week 18, 46.7% (95% CI, 40.2–54) at 1 year, and 56.9% (95% CI, 50–68.4) at 2 years. Ninety-five patients (26.3%) discontinued everolimus before 2 years; 103 (28.5%) had <2 years of follow-up at study cutoff, and 40% were exposed to everolimus for ≥2 years. An analysis classifying discontinued patients as nonresponders showed an RR of 30.2% (95% CI, 25.5–35.2; N = 361) at week 18, 38.8% (95% CI, 33.7–44.1; N = 358) at 1 year, and 41% (95% CI, 34.6–47.7; N = 229) at 2 years, suggesting sustained benefit over time. The incidence of grade 3/4 adverse events (AEs) (any cause) was 40.2%, and 13% discontinued because of AEs (pneumonia [1.7%] and stomatitis [1.4%]). Two deaths were suspected to be treatment-related (pneumonia and septic shock). Conclusions Sustained reductions in TSC-associated treatment-refractory seizures over time were achieved with adjunctive everolimus. The safety profile was consistent with the core phase with no new safety concerns. Classification of evidence This study provides Class IV evidence that long-term everolimus therapy reduces SF in patients with TSC-associated treatment-refractory seizures.
Archive | 2005
John R. Pollard; Jacqueline A. French
Archive | 2018
Allan Krumholz; Shlomo Shinnar; Jacqueline A. French; Gary S. Gronseth
Archive | 2018
Jacqueline A. French; Andres M. Kanner; Gary S. Gronseth
Archive | 2017
Allan Krumholz; Samuel Wiebe; David Gloss; Shlomo Shinnar; Jacqueline A. French
Neuropediatrics | 2017
G. Wiegand; Tilman Polster; Christoph Hertzberg; A. Wiemer-Kruel; Jacqueline A. French; P. Fan; P. de Vries; Noah Berkowitz; Alexandra Vaury; Severine Peyrard; Paolo Curatolo
European Journal of Paediatric Neurology | 2017
Paolo Curatolo; David Neal Franz; John A. Lawson; Zuhal Yapici; Hiroko Ikeda; Tilman Polster; Rima Nabbout; P.J. de Vries; Dennis J. Dlugos; Jenna Fan; Severine Peyrard; Diana Pelov; Maurizio Voi; Jacqueline A. French
Archive | 2012
Susan S. Ellenberg; Jacqueline A. French
Archive | 2012
John R. Pollard; Susan S. Ellenberg; Jacqueline A. French