The most cited works in epilepsy: Trends in the ������Citation Classics������ *George M. Ibrahim, yO. Carter Snead III, *James T. Rutka, and *Andres M. Lozano *Division of Neurosurgery, Toronto Western Hospital and The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada and yDivision of Neurology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada SUMMARY The number of times that a published article is cited is one indicator of its scientific impact. An article is termed a ������Citation Classic������ once it has accumulated more than 400 citations. Trends in these highly cited works allow projection of future directions of high-impact research within a field. Herein, we identified 89 articles in the field of epilepsy published in 35 different journals that have been cited more than 400 times (citation range 401��� 3,749). The journal that published the greatest number of Citation Classics was Epilepsia (9 articles with 656 mean citations per article). Laboratory studies constituted the fastest growing area of highly cited epilepsy research, whereas clinical studies showed a bimodal distribution in representation among Citation Classics. There were also considerably fewer epilepsy-specific Citation Classics compared to other disciplines. In this study, we find that the Citation Classics of epilepsy comprise a heteroge- neous group of articles and that changes in the trends of these highly cited works represent the evolution of epi- lepsy research over time. The results of this study should inform the academic community and provide a guide of essential literature for scientists who are engaged in epi- lepsy research. KEY WORDS: Epilepsy, Citations, Citation Classics. One indicator of the scientific impact of a published work is the number of times that it has been cited by other publica- tions. An article is termed a ������Citation Classic������ once it has been cited more than 400 times (Garfield, 1987). Identifying these highly cited works is important for several reasons. First, the Citation Classics represent the highest impact work in a given field, and familiarity with this literature is essential for clinicians and scientists involved in the area of study. Secondly, analyzing trends in Citations Classics can indicate the direction in which a field of study is headed, and offer insights into highly active areas of research within the discipline. Furthermore, this literature may be used for education purposes to develop relevant curricula for stu- dents in medicine and the basic sciences. Citation Classics have been reported previously for neu- rologic conditions such as Parkinson���s disease (Ponce & Lozano, 2011), psychiatric conditions such as depression (Lipsman & Lozano, 2011), as well as broad disciplines including neurosurgery (Ponce & Lozano, 2010), trauma (Ollerton & Sugrue, 2005), and ophthalmology (Ohba & Nakao, 2010). Herein, we report the Citation Classics within the field of epilepsy. We analyze trends in this highly cited literature and present a cross-disciplinary analysis of Cita- tion Classics in selected neurologic fields. Methods Search strategy To identify epilepsy-specific Citation Classics, we per- formed a general citation search used Harzing���s Publish or Perish, an internet-based search engine without time restric- tions using the search terms ������epilepsy,������ ������epilepsies,������ ������epi- leptic,������ ������epilepticus,������ ������seizures,������ and/or ������seizure������ (Harzing, 2007). We designed the search strategy such that it was epilepsy-specific, by using terms related to epilepsy or seizures however, this strategy may not be sensitive for all epilepsy-related articles. For instance, the search strategy may miss general neuroscience articles that have implica- tions for epilepsy research. We, therefore, coin our results the ������epilepsy-specific������ Citation Classics. The search engine was accessed on November 25, 2011. Criteria for inclusion in the study were relevance to the field of epilepsy and pub- lication in a peer-reviewed journal. The full-length articles of the identified Citation Classics were obtained and reviewed. We subsequently performed a validation search to find articles that may not have been identified through the initial search strategy by searching by name for well-known pio- neers of epilepsy research as well as all current and former Accepted February 13, 2012 Early View publication March 29, 2012. Address correspondence to Andres M. Lozano, Toronto Western Hospi- tal, 399 Bathurst St., Toronto, ON M5G, Canada. E-mail: lozano@uhnre- search.ca Wiley Periodicals, Inc. �� 2012 International League Against Epilepsy Epilepsia, 53(5):765���770, 2012 doi: 10.1111/j.1528-1167.2012.03455.x CRITICAL REVIEW AND INVITED COMMENTARY 765

presidents and editors-in-chief of epilepsy societies and journals (societies: International League Against Epilepsy, American Academy of Neurology, and American Associa- tion of Neurological Surgeons journals: Epilepsia, Epilepsy Research, and Neurology). Outcomes from the validation search were cross-referenced with the original search strat- egy to identify articles cited more than 400 times that were initially missed. The Citation Classics were grouped and analyzed into three categories: (1) laboratory investigations (2) clinical research and (3) reviews or classification studies, which organize existing knowledge into classification systems. Relationships between continuous variables were identified using linear regression p-values 0.05 were considered statistically significant. Analysis was performed using SAS 9.3 statistical software (SAS Institute, Cary, NC, U.S.A.). Results Search results The search criteria yielded a total of 101 papers with more than 400 citations. Of these, 12 results were discarded because of irrelevance to epilepsy (i.e., ������Search and seizure: a treatise on the Fourth Amendment������) or publication in a format other than a peer-reviewed journal. Therefore, a total of 89 epilepsy-specific ������Citation Classics������ were identified with 648 average citations per paper (citation range 401��� 3,749). The top 10 epilepsy-specific Citation Classics are presented in Table 1. A full list of the Citation Classics can be found in Table S1. When the validation search was per- formed, no additional epilepsy-specific articles were identi- fied. A MEDLINE/PubMed search using the same search terms yielded more than 129,700 peer-reviewed articles in the general medical literature. Therefore, the identified Citation Classics represent approximately 0.07% of papers published in the field of epilepsy. This roughly translates into one article per 1,400 epilepsy-specific papers that will go on to become a Citation Classic. The Citation Classics were published in 35 different jour- nals (Table 2). The journal that published the highest num- ber of highly cited papers in epilepsy was Epilepsia (9 papers with an average of 656 citations per paper). There was a weakly positive correlation between journal���s impact factor and the number of total citations accumulated (Pear- son correlation coefficient 0.38 p = 0.02). In addition, there was a moderately positive correlation between a journal���s impact factor and the number of Citation Classics published therein (Pearson correlation coefficient 0.42 p = 0.01). Categories and trends Of the 89 identified Citation Classics, 48 were laboratory investigations, 27 pertained to clinical research, and 14 arti- cles were reviews or described novel classification systems (Fig. 1). The fastest growing category within the cohort of highly cited epilepsy research was the laboratory investigations. Within this group, 37 articles (77%) involved molecular biology techniques, whereas 11 articles (23%) involved electrophysiologic recordings and/or cortical stimulation. All molecular studies were published after 1980, whereas 36% of electrophysiologic studies were published before 1980. Only one electrophysiologic study (9%) was pub- lished after 1995, compared to 21 molecular studies (57%). Ten of the molecular studies (27%) addressed neurotrans- mitters, excitability, and inhibition in epilepsy six studies (16%) presented novel information about ion channels in epilepsy and four articles (11%) reported on data where kainic acid was used to induce experimental seizures. Clinical research studies demonstrated a bimodal distri- bution over time. The first peak for highly cited epidemio- logic studies occurred in the 1970s and a second surge Table 1. Top 10 epilepsy-specific Citation Classics Rank Article Citations 1 Racine RJ. (1972) Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281���294 3,749 2 Kwan P, Brodie MJ. (2000) Early identification of refractory epilepsy. N Engl J Med 342:314���319 1,419 3 Ben-Ari Y. (1985) Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 14:375���403 1,351 4 Morgan JI, Cohen DR, Hempstead JL, Curran T. (1987) Mapping patterns of c-fos expression in the central nervous system after seizure. Science 237:192���197 1,303 5 Nibuya M, Morinobu S, Duman RS. (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatment. J Neurosci 15:7539���7547 1,193 6 Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH. (1997) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17:3727���3738 1,162 7 Engel J. (2001) A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 42:796���803 1,123 8 Hauser WA, Annegers JF, Kurland LT. (1993) Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935���1984. Epilepsia 34:453���468 996 9 Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC. (1990) Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation. Cell 61:931���937 961 10 Wiebe S, Blume WT, Girvin JP, Eliasziw M. (2001) A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Eng J Med 345:311���318 911 766 G. M. Ibrahim et al. Epilepsia, 53(5):765���770, 2012 doi: 10.1111/j.1528-1167.2012.03455.x