Correspondence CAN PATIENTS WITH EPILEPSY PREDICT THEIR SEIZURES? To the Editor: We read the article by Haut et al with interest.1 The authors report on the ability of some patients with epilepsy to predict the occurrence of their seizures As suggested by the authors, this ability may rely on prodromes or warning and initial symptoms Preictal dysphoria is a phenomenon well described by patients and their relatives, but the frequency, duration, and clinical features have been only occasionally investigated The last systematic study specifically dedicated to this subject was published in 1986.2 It is evident that mood changes preceding the occurrence of seizures represent a neglected area of research in epileptology and neuropsychiatry of epilepsy that, conversely, may have important clinical implications Research concerning seizure-alerting dogs is also of interest.3 It is possible that this phenomenon could be interlinked with preictal dysphoria—that dogs’ behaviors are influenced by specific mood changes of the owner occurring in the preictal phase It is now accepted that the end of the seizure is not the end of the problem,4 but what precedes the seizure can be equally interesting Marco Mula, MD, Francesco Monaco, MD, Novara, Italy Disclosure: The authors report no conflicts of interest Reply from the Authors: We appreciate the interesting comments by Drs Mula and Monaco The role of mood changes preceding a seizure is an intriguing issue that has received little recent attention We agree that the ability of patients to successfully predict their seizures may well be related, at least in part, to the emotional content of the preictal phase Certainly this is an area of investigation that merits prospective evaluation, and one that we plan to incorporate in our follow-up studies Furthermore, the possible connection of mood changes preceding a seizure and the abili494 Neurology 69 July 31, 2007 ties of seizure-alert dogs is intriguing and biologically plausible Sheryl R Haut, Charles B Hall, Aaron J LeValley, Richard B Lipton, Bronx, NY Disclosure: The authors report no conflicts of interest Copyright © 2007 by AAN Enterprises, Inc Haut SR, Hall CB, LeValley AJ, Lipton RB Can patients with epilepsy predict their seizures? Neurology 2007;68:262–266 Blanchet P, Frommer GP Mood change preceding epileptic seizures J Nerv Ment Dis 1986;174:471– 476 Strong V, Brown SW, Walker R Seizure-alert dogs: fact or fiction? Seizure 1999;8:62– 65 Kanner AM, Soto A, Gross-Kanner H Prevalence and clinical characteristics of postictal psychiatric symptoms in partial epilepsy Neurology 2004;62:708 –713 ENCEPHALOPATHY, STROKE, AND MYOCARDIAL INFARCTION WITH DMSO USE IN STEM CELL TRANSPLANTATION To the Editor: The topical report by ChenPlotkin et al shows the probable role of DMSO in complications due to stem cell transplantation.1 This is analogous to encephalopathy induced by propylene glycol-containing IV drugs.2 In the case of DMSO, this could have been caused by metabolic formation of sulfite which is harmful, for example to mitochondria and heme synthesis.3 With new therapeutic methods, the toxicity of excipients should be further investigated so that the positive effects of treatment are not lost Heikki Savolainen, Tampere, Finland Disclosure: The author reports no conflicts of interest Reply from the Authors: We thank Dr Savolainen for the comments on our article The phenomenon we described of profound encephalopathy during or shortly after DMSO infusion implies a toxic effect without indicating a clear mechanism However, the myocardial and cerebral infarcts suggest additional vascular ischemic causes, which are different from the metabolic effects described in propylene glycol toxicity Work in an animal model using selective injections of various solvents into the swine equivalent of the carotid artery (rete mirabile) has demonstrated that DMSO, more than similar solvents (DMI, ethyl lactate, glycofurol 74, NMP, and solketal) may cause prolonged vasospasm.4 We postulate that this vasospasm, in turn, may result in ischemia and infarction of tissue Alice S Chen-Plotkin, Keith A Vossel, Martin A Samuels, Ming Hui Chen, Boston, MA Disclosure: The authors report no conflicts of interest Copyright © 2007 by AAN Enterprises, Inc Chen-Plotkin AS, Vossel KA, Samuels MA, et al Encephalopathy, stroke and myocardial infarction with DMSO use in stem cell transplantation Neurology 2007;68:859 – 861 Wilson KC, Reardon C, Theodore AC, et al Propylene glycol toxicity: a severe iatrogenic illness in ICU patients receiving IV benzodiazepines Chest 2005;128: 1674 –1681 Savolainen H, Tenhunen R Inhibition of heme synthase in brain and liver by low-level peroral sulfite exposure Res Commun Chem Pathol Pharmacol 1982; 36:511–514 Dudeck O, Jordan O, Hoffmann KT, et al Organic solvents as vehicles for precipitating liquid embolics: a comparative angiotoxicity study with superselective injections of swine rete mirabile Am J Neuroradiol 2006; 27:1900 –1906 THE IMPACT OF LITIGATION ON NEUROLOGIC RESEARCH To the Editor: Racette et al complain that litigation interferes with scientific research.1 Unfortunately, their article offers a one-sided, incomplete picture of the interaction between scientific research and the law, and their proposals are illconsidered Although the authors complain about the expense incurred in responding to subpoenas for data underlying their Alabama study, they fail to disclose that the welder screenings for their study were funded by plaintiffs’ attorneys as part of an effort to solicit personal-injury clients.2 Defendants served subpoenas to obtain the study’s underlying data only after plaintiffs’ counsel heavily relied on the study in the litigation Contrary to their minimal disclosure, the authors were not disinterested researchers inadvertently caught up in litigation The authors collaborated with plaintiffs’ counsel so closely that counsel invoked litigation privileges to cloak the work in secrecy The authors also fail to mention that much of the cost of complying with the subpoenas resulted from their own actions The subpoenas were served with offers to redact individual identifiers, reimburse reasonable expenses, and to agree to nondisclosure and nonpublication of data The authors spurned these offers, and filed briefs seek- ing to block all access The Court, after carefully weighing all parties’ interests, required production of limited, redacted data, with compensation for reasonable expenses, as originally offered The costs complained of were largely selfinflicted Basic norms of science favor openness and discourage secrecy in research The scientific community has increasingly demanded transparency from investigators Many leading journals require raw data and questionnaires to be submitted, either in peer-review or upon acceptance Research funded by the NIH is subject to federal law that makes underlying data subject to public disclosure,3 and the National Research Council has urged sharing research data, especially when relevant to public policy.4 As demonstrated in the welding cases, judges appropriately have discretion to protect researchers’ legitimate interests, while ensuring that litigants can discover and examine studies that may be offered against them The authors’ proposals would chill participation by outstanding senior academic physicians and create vacuums in courtrooms, which will be filled by less-qualified witnesses The proposals undermine physicians’ civic obligations to provide their expertise, properly compensated, to all participants in the judicial system.5 Finally, the authors’ vague proposal to limit industrysponsored support for specific projects threatens to prevent companies from funding research, a demand often made by the very plaintiffs’ lawyers who supported Dr Racette’s work Nathan A Schachtman, Philadelphia, PA Disclosure: Nathan A Schachtman is a member of McCarter & English LLP, Philadelphia, PA Mr Schachtman, in his capacity as legal counsel for welding defendants, was responsible for serving the subpoenas discussed in the editorial piece by Drs Racette and Perlmutter, and their legal counsel He has prepared and tried hundreds of cases involving epidemiologic data, involving various disease outcomes, including neurologic diseases and disorders The opinions in this letter are his, and not necessarily those of his clients or his firm Reply from the Authors: We appreciate Mr Schachtman’s interest in our recent article However, it is important to point out the errors included in his letter Mr Schachtman inaccurately alleges that we provided “minimal disclosure” and collaborated with plaintiffs’ counsel.6 As originally disclosed in our article,2 our University was paid by attorneys to perform medical screenings in Alabama of patients exposed to welding The data that we collected were subsequently retrospectively examined and the results Neurology 69 July 31, 2007 495 published There was no funding or collaboration with attorneys as to any aspect of the design, execution, or publication of the study Furthermore, Mr Schachtman suggests that plaintiffs’ counsel’s invocation of privileges for patients who did not file lawsuits proves an illicit collaboration between plaintiffs’ counsel and our research team Various legal privileges protect patients’ medical data (see, e.g., 10 A.L.R 4th 552, Wakefield WE Physician-patient privilege as extending to patient’s medical or hospital records; 2007) Pleadings filed in the multidistrict litigation indicate that none of the Alabama patients we examined became plaintiffs in the multidistrict litigation The patient data demanded by the welding defendants’ subpoenas related entirely to patients who were not plaintiffs in the underlying litigation Counsel for these patients who did not file suit legitimately asserted litigation privileges to protect their medical data Seeking protection of applicable privileges is procedural for lawyers and not evidence of a conspiracy Mr Schachtman stretches credibility by asserting that much of the cost of complying with subpoenas resulted from our “own actions.” His suggestion that we could have avoided litigation costs and simply complied with his clients’ subpoenas is, and was, an unacceptable outcome, in a case where neither the University nor its researchers are parties or designated experts He and his clients’ primary interest in this research are to discredit it in a court of law, which is neither the forum nor the outcome we could abide willingly Mr Schachtman’s clients served subpoenas found by a United States District Judge to be overbroad and burdensome A few examples included copies of all patient videos; all grant applications by study authors; all drafts of the published version of the study; all editor and peer review comments to drafts of the study; and all data analyses outputs.2,6 Failing to object to these unreasonable requests would have consumed greater resources, jeopardized patient confidentiality, and further delayed future research Mr Schachtman naively equates the peerreview system and scientific openness with legal review of data by medical experts paid large sums of money to discredit research The former advances science and brings needed treatments to patients The intent of the latter frequently is to 496 View publication stats Neurology 69 July 31, 2007 intimidate scientists from pursuing new avenues of research that might prove detrimental to one side of a lawsuit Reasonable limitations on access to researchers’ time and data would prevent investigators from abandoning promising research leads However, researchers must also take responsibility for their actions and decide if their own personal gain trumps patients’ interests Despite Mr Schachtman’s claims to the contrary, it is reasonable to expect that a researcher avoid personal financial conflicts when conducting research We owe our patients acknowledgment of the problem and correction of this abusive system Brad A Racette, Ann Bradley, Carrie A Wrisberg, Joel S Perlmutter, St Louis, MO Disclosure: After the publication of the abstract to a 2001 manuscript on welding, Dr Racette provided consultation and received personal compensation for one meeting each with counsel representing defendants and plaintiffs for welding-related medical matters not pertaining to any multidistrict litigation, for consulting compensation totaling $2,000 Dr Racette received $229,631 paid to Washington University in St Louis from the Welder Health Fund into an account controlled by Dr Racette The Welder Health Fund was created by Gulf States Trial Attorneys to support medical screening of welders for Parkinson disease Copyright © 2007 by AAN Enterprises, Inc Racette BA, Bradley A, Wrisberg CA, Perlmutter JS The impact of litigation on neurologic research Neurology 2006;67:2124 –2128 Racette BA, Tabbal SD, Jennings D, Good L, Perlmutter JS, Evanoff B Prevalence of parkinsonism and relationship to exposure in a large sample of Alabama welders Neurology 2005;64:230 –235 Public Law 105–277 (1999) (requiring the Office of Management and Budget to promulgate regulations that required federal agencies awarding research contracts to ensure that “all data produced under a federal award will be made available to the public”); see also OMB Circular A-110, Uniform Administrative Requirements for Grants and Agreements with Institutions of Higher Education, Hospitals, and Other NonProfit Organizations, Federal Register 64:5684 (Feb 4, 1999) Fienberg SE, Martin ME, Straf ML Sharing Research Data Washington, DC: National Academies Press, 1985 American College of Physicians Guidelines for the Physician Expert Witness Ann Intern Med 1990;113: 789 United States District Court for the Northern District of Ohio Eastern Division MDL#1535, 2007 United States District Court for the Eastern District of Missouri, Eastern Division, 4:05MC165SNL, 2005 ... superselective injections of swine rete mirabile Am J Neuroradiol 2006; 27:1900 –1906 THE IMPACT OF LITIGATION ON NEUROLOGIC RESEARCH To the Editor: Racette et al complain that litigation interferes... scientific research. 1 Unfortunately, their article offers a one-sided, incomplete picture of the interaction between scientific research and the law, and their proposals are illconsidered Although the. .. counsel invoked litigation privileges to cloak the work in secrecy The authors also fail to mention that much of the cost of complying with the subpoenas resulted from their own actions The subpoenas