Author
John T. Langfitt
Other affiliations: Mayo Clinic, University of Rochester Medical Center, University of California, Los Angeles
Bio: John T. Langfitt is an academic researcher from University of Rochester. The author has contributed to research in topics: Epilepsy & Epilepsy surgery. The author has an hindex of 37, co-authored 73 publications receiving 5413 citations. Previous affiliations of John T. Langfitt include Mayo Clinic & University of Rochester Medical Center.
Papers published on a yearly basis
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TL;DR: Whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL) is sought and among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AEDtreatment alone.
Abstract: Context Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death. Objective We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL). Design, Setting, and Participants The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged ≥12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. Intervention Receipt of continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. Main Outcome Measures The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation. Results Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio = ∞; 95% CI, 11.8 to ∞; P Conclusions Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution. Trial Registration clinicaltrials.gov Identifier: NCT00040326
902 citations
TL;DR: This critical review summarizes known risks associated with refractory epilepsy, provides practical clinical recommendations, and indicates areas for future research.
463 citations
TL;DR: To determine the frequency and determinants of subnormal global cognitive function in a representative, community‐based sample of children prospectively identified at the time of initial diagnosis of epilepsy.
Abstract: Summary
Purpose: To determine the frequency and determinants of subnormal global cognitive function in a representative, community-based sample of children prospectively identified at the time of initial diagnosis of epilepsy.
Methods: In children enrolled with newly diagnosed epilepsy and followed a median of 10.5 years, level of cognitive function (within normal, borderline, mild, moderate to severe mental retardation (MR), neurologically devastated, and impaired but not further classified (NFC)) was determined based upon neurologists' and school records, repeated parental interviews, and, in over half the participants, standardized neuropsychological testing. For multivariable analyses, subnormal cognitive function was designated as consistent with a full scale IQ < 80.
Results: Global cognitive function was considered within normal, N = 451 (73.6%), borderline, N = 31 (5.1%), mild MR, N = 21 (3.4%), more severe MR, N = 45 (7.3%), devastated, N = 29 (4.7%), and impaired-NFC, N = 36 (5.9%). Age at onset <5 years, symptomatic etiology, epileptic encephalopathy, remission status and current AED treatment were each strongly associated with level of cognitive function (all p-values <0.0001). In a multivariable logistic regression model, all variables except remission status independently contributed to subnormal global cognitive function.
Discussion: Evidence of subnormal global cognitive function is apparent in approximately one of four children with epilepsy. Young age at onset, symptomatic cause, epileptic encephalopathy, and continued treatment, despite their strong intercorrelations, are independently associated with this outcome.
309 citations
TL;DR: Hippocampal atrophy and a history of absence of generalized tonic clonic seizures were the sole predictors of 2-year remission, and only for medial temporal resections.
Abstract: Background: In a seven-center prospective observational study of resective epilepsy surgery, the authors examined probability and predictors of entering 2-year remission and the risk of subsequent relapse. Methods: Patients aged 12 years and over were enrolled at time of referral for epilepsy surgery, and underwent standardized evaluation, treatment, and follow-up procedures. The authors defined seizure remission as 2 years completely seizure-free after hospital discharge with or without auras, and relapse as any seizures after 2-year remission. The authors examined type of surgery, seizure, clinical and demographic variables, and localization study results with respect to prediction of seizure remission or relapse, using χ 2 and proportional hazards analysis. Results: Of 396 operated patients, 339 were followed over 2 years, and 223 (66%) experienced 2-year remission, not significantly different between medial temporal (68%) and neocortical (50%) resections. In multivariable models, only absence of generalized tonic-clonic seizures and presence of hippocampal atrophy were significantly and independently associated with remission, and only in the medial temporal resection group. Fifty-five patients relapsed after 2-year remission, again not significantly different between medial temporal (25%) and neocortical (19%) resections. Only delay to remission predicted relapse, and only in medial temporal patients. Conclusion: Hippocampal atrophy and a history of absence of generalized tonic clonic seizures were the sole predictors of 2-year remission, and only for medial temporal resections.
302 citations
TL;DR: A substantial proportion of localization-related epilepsy may not become clearly intractable for many years after onset, especially true of epilepsy of childhood and early adolescent onset.
Abstract: Background: Much remains unknown about the natural history of intractable localization-related epilepsy, including how long it typically takes before intractability becomes evident. This information could guide the design of future studies, resolve certain discrepancies in the literature, and provide more accurate information about long-term prognosis. Methods: Individuals evaluated for resective surgery for refractory localization-related epilepsy were prospectively identified at the time of initial surgical evaluation at seven surgical centers (between 1996 and 2001). The latency time between onset of epilepsy and failure of second medication and history of remission (≥1 year seizure-free) before surgical evaluation were examined with respect to age at onset, hippocampal atrophy, febrile seizures, and surgical site. Results: In the 333 patients included in the analysis, latency time was 9.1 years (range 0 to 48) and 26% reported a prior remission before surgery. A prior remission of ≥5 years was reported by 8.5% of study participants. Younger age at onset was strongly associated with longer latency time ( p p Conclusions: A substantial proportion of localization-related epilepsy may not become clearly intractable for many years after onset. This is especially true of epilepsy of childhood and early adolescent onset. If prospective studies confirm these findings and the underlying mechanisms behind these associations become understood, this raises the possibility of considering interventions that might interrupt such a process and some day prevent some forms of epilepsy from becoming intractable.
278 citations
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9,362 citations
TL;DR: Progress made during the first half of the Human Connectome Project project in refining the methods for data acquisition and analysis provides grounds for optimism that the HCP datasets and associated methods and software will become increasingly valuable resources for characterizing human brain connectivity and function, their relationship to behavior, and their heritability and genetic underpinnings.
4,388 citations
TL;DR: It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules to achieve sustained seizure freedom.
Abstract: To improve patient care and facilitate clinical research, the International League Against Epilepsy (ILAE) appointed a Task Force to formulate a consensus definition of drug resistant epilepsy. The overall framework of the definition has two "hierarchical" levels: Level 1 provides a general scheme to categorize response to each therapeutic intervention, including a minimum dataset of knowledge about the intervention that would be needed; Level 2 provides a core definition of drug resistant epilepsy using a set of essential criteria based on the categorization of response (from Level 1) to trials of antiepileptic drugs. It is proposed as a testable hypothesis that drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. This definition can be further refined when new evidence emerges. The rationale behind the definition and the principles governing its proper use are discussed, and examples to illustrate its application in clinical practice are provided.
3,017 citations
TL;DR: An anatomical model is presented that indicates the location of the language areas and the most consistent functions that have been assigned to them and the implications for cognitive models of language processing are considered.
1,700 citations
TL;DR: This research presents a novel and scalable approach called “informed consent” that aims to provide real-time information about the pros and cons of surgery on the basis of prior history and once-in-a-lifetime data.
Abstract: *Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China; yInstitute for Children and Adolescents with Epilepsy-IDEE, University Hospital of Lyon (HCL) and Inserm U821, Lyon, France; zDepartment of Biology, Northern Illinois University, DeKalb, Illinois, U.S.A.; xEpilepsy Unit, Western Infirmary, Glasgow, United Kingdom;{GH Sergievsky Center, Columbia University, New York, New York, U.S.A.; #Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.A.; **The Saul R. Korey Department of Neurology, Dominick P. Purpura Department of Neuroscience and Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; yyClinical Trial Center, Institute of Neurology IRCCS C. Mondino Foundation, and Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; zzDepartment of Clinical Neurosciences, University of Calgary, and Hotchkiss Brain Institute, Calgary, Alberta, Canada; and xxNYU Comprehensive Epilepsy Center, New York, New York, U.S.A.
1,639 citations