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Patient and caregiver perspectives on seizure prediction
Epilepsy & Behavior 19 (2010) 474–477
Contents lists available at ScienceDirect
Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Patient and caregiver perspectives on seizure prediction Susan Arthurs a,⁎, Hitten P. Zaveri b, Mark G. Frei c, Ivan Osorio d a
Alliance for Epilepsy Research, P.O. Box 446, Dexter, MI 48130-0446, USA Department of Neurology, Yale University, New Haven, CT 06520, USA c Flint Hills Scientific LLC, 2513 Via Linda Drive, Lawrence, KS 66047, USA d University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA b
a r t i c l e
i n f o
Article history: Received 9 June 2010 Revised 5 August 2010 Accepted 9 August 2010 Available online 20 September 2010 Keywords: Seizure Epilepsy Patient with epilepsy Caregiver Patient survey Seizure prediction Implantable device
a b s t r a c t One of the goals of the Fourth International Workshop on Seizure Prediction was to provide an opportunity for patients with epilepsy and their caregivers to voice their perspectives on seizure prediction and related matters toward the goal of influencing the design of solutions. In an attempt to fulfill this goal, a survey of patients and caregivers, who often make or influence patient choices, was conducted on issues pertaining to living with epilepsy, epilepsy treatments, seizure prediction, and the use of implantable devices for the control of seizures. The results of this survey are reported here. © 2010 Elsevier Inc. All rights reserved.
1. Introduction It is estimated that as many as 60 million people in the world, and 3 million in the United States, have epilepsy. Furthermore, it was reported in a prior survey [1] that only 15% of the responding patients with epilepsy achieve full control of seizures without side effects through the use of antiepileptic drugs (AEDs). This lends support to the view that achieving full control of seizures without side effects through AEDs alone may be difficult, if not impossible, for many patients. Epilepsy affects millions more as family members and caregivers struggle to assist those with epilepsy endure this chronic disorder. An examination of the causes of disability, injury, and death in patients with medically intractable epilepsy finds seizure unpredictability to be the most crippling aspect and the one that negatively impacts safety, life span, and quality of life. The considerable progress in technology in the modern era has allowed researchers to expand their approaches to treating epilepsy from single-discipline pharmacological agents to multidiscipline efforts to detect or predict seizures and stop them with devices. The Fourth International Workshop on Seizure Prediction (IWSP4), an interdisciplinary meeting of investigators, was held June 4–7, 2009, in Kansas City, MO, USA, to discuss the status of the field of seizure
⁎ Corresponding author. P.O. Box 446, Dexter, MI 48130-0446, USA. Fax: + 1 734 4264877. E-mail address: [email protected] (S. Arthurs). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.08.010
prediction and related areas. One of the multiple goals of this workshop was to allow patients and their caregivers to provide their perspectives on seizure prediction toward the additional goal of influencing solutions. Patient and caregiver perspectives were determined by way of a survey. Caregivers were included in this survey because epilepsy impacts them as well as patients, and caregivers often influence the decisions of patients with epilepsy or make them on their behalf. This article reports the results of the survey of patients and caregivers on issues pertaining to living with epilepsy, treatments, and implantable devices for the control of seizures.
2. Methods A survey comprising 19 questions was designed and made available through a patient page on the IWSP4 website (http:// www.iwsp4.org). Three additional questions (zip code, numeric portion of street address or postal box number, and first name) were used to code individual submissions while protecting privacy; the zip code provided the geographic location of respondents, information that has some value in the interpretation of results. Respondents could complete and submit the survey online or could download, print, complete, and mail it. The survey was promoted both on the IWSP4 website and by the Epilepsy Foundation of America (EFA), which posted a news article on the EFA website with a link to the survey on the IWSP4 website. The survey was open for 6 weeks beginning April 1, 2009.
S. Arthurs et al. / Epilepsy & Behavior 19 (2010) 474–477
3. Results
475
Table 2 Side effects and problems reported from current treatments for epilepsy.
Eighty-nine responses were received, 84 through the Internet and 5 via mail. All responses were from the United States, with the zip codes being evenly distributed geographically from 01027 to 99703. Patients with epilepsy constituted 62.9% (56) of the respondents, parent caregivers 33.7% (30), and other family member caregivers 3.4% (3). There were no submissions from unrelated caregivers. Submissions for all patients aged 15 and younger (21) and an additional 11 responses were from caregivers. Survey questions are stated below and responses received are summarized. The survey and responses obtained are also fully documented in Tables S1–S22 (see Appendix A). Of the patients referenced in the submissions, 61 (68.5%) were female and 28 (31.5%) male. Patients ranged in age from 2 to 87 (Table S3 [see Appendix A]). Duration of epilepsy ranged from 0 to 72 years, with half reporting durations of 15 years or longer.
3.1. Seizure frequency, effects of current treatments, and burdens of epilepsy Survey question (select one answer): “Seizure frequency –.” In response to the survey question on seizure frequency, more than half of the patients (58.3%) reported experiencing one or more seizures per month (Table 1). Survey question (comment/essay answer): “What side effects or problems do you experience from epilepsy treatments?” Patients experienced a variety of side effects and problems from their epilepsy treatments (Table 2). Many respondents listed more than one side effect or problem, with the average being 2.5 problems per patient. The most commonly cited problems were tiredness and issues with memory. Fourteen respondents (15.9%) reported no problems. We note that some of these problems may have other causes, such as brain damage underlying the epilepsy or effects of interictal and ictal epileptic activity, and may not be due to the current treatment being received. Survey question (comment/essay answer): “Whether you are an epilepsy patient or caregiver, describe the effects of epilepsy and epilepsy treatments on your quality of life.” Epilepsy and treatments for epilepsy can have a major impact on the quality of life for both patients and caregivers (Table 3). Many respondents reported multiple issues with having epilepsy in their life. The average number of effects of epilepsy and epilepsy treatments on quality of life was 1.75. Survey question (comment/essay answer): “In your opinion, what is the most difficult part of having epilepsy?” The most difficult part of having epilepsy was fear for 42 respondents (48.3%); social issues for 38 (43.7%); medical issues for 15 (17.2%); inability to drive for 13 (14.9%); work problems for 7 (8.0%); and other for 6 (6.9%). Thirtytwo respondents (36.8%) had more than one “most” difficult issue. One respondent stated: “One of the worst things about seizures is that you don't know when one is coming. We live in a constant state of alert. It's hard to relax.”
Side effects
Number of patients
Tiredness Memory problems None Dizziness Mood problems Seizures continue Concentration issues Headaches Appetite Shaking Other side effects
31 15 14 9 9 8 7 7 6 6 b 6 each
3.2. Looking ahead to seizure warnings and implantable treatment devices Survey question (select yes or no): “Would you want advanced warnings of your seizures?” Eighty-four (95.5%) responded “yes.” In contrast, however, one parent caregiver noted, “Our son has hundreds of seizures a day; knowing when they come is not helpful.” Survey question (select one answer): “From 1 to 5, with 5 being the highest, what value do you place on the ability to predict or warn of seizures?” Forty-three respondents (48.3%) placed the highest value (5) on the ability to predict or warn of seizures. A high value was indicated by 25 (28.1%), medium value by 20 (22.5%), low value by 1 (1.1%), and lowest value by 4 (4.5%). Survey question (select yes or no): “Would you want treatment to be automatically triggered by the prediction of seizures?” Sixty-five respondents (74.7%) indicated interest in having treatment triggered automatically by seizure warnings. (Treatments might include electrical stimulation, drug injection, or cooling in the area of the brain where the seizures originate.) Survey question (select one answer): “If you were warned of seizures, what length of time would be best?” The preferred length of seizure warning time was 3 to 5 minutes. The reasons provided for this duration suggested that a prime concern of the respondents was safety. This preferred duration would allow patients to reach a safe place, obtain help, or remove themselves from potentially embarrassing situations. Longer durations were seen as being more stressful and, thus, having a negative impact on quality of life. Survey question (comment/essay answer): “What are your feelings about having a device implanted in your brain?” When given the opportunity to explain their response, both patients and caregivers qualified their answers: 37 (43.0%) thought it might be acceptable if it would work, 28 (32.6%) wanted more information, 10 (11.6%) indicated that it does not appeal to them at present. Only 8 (9.3%) categorically stated “no.” Survey question (comment/essay answer): “If you do not want to have a device implanted in your brain, please provide the reason.” Of the 46 respondents who were not sure about or not interested in having devices implanted in the brain, the vast majority (31, 67.4%) cited fear Table 3 Effect of epilepsy and current epilepsy treatments on quality of life.
Table 1 Frequency of seizures experienced by patients. Seizure frequency
Number (%) of patients
b 1/year 1–6/year 1/month 1 every other week 1/week 1/day N 1/day
18 19 14 7 10 2 19
(20.2) (21.3) (15.7) (7.9) (11.2) (2.2) (21.3)
Effect on quality of life
Number of respondents
Fear Inability to drive Social issues Work problems Depression Fatigue School issues Stressed Other effects
25 17 13 13 12 11 8 7 b7 each
476
S. Arthurs et al. / Epilepsy & Behavior 19 (2010) 474–477
as the reason. Among the other 15 (32.6%), 7 (15.2%) wished to have more information; 3 (6.5%) found it not appealing at present; and 5 (10.9%) had other reservations. One respondent commented, “I don't want to take any chances of being worse than I already am.” Survey question (select yes or no): “Would you be willing to participate in clinical trials for implanted devices?” When asked to categorically state if they would be willing to participate in clinical trials for implanted devices, that is given only “yes” or “no” responses as options, 54 (65.9%) responded “no.” Further insight into the perspectives provided can be gained by cross-referencing the responses to survey questions. When patient gender was cross-referenced with patient/caregiver respondent, three and a half times as many female patients responded as male patients (44 vs 12, respectively), whereas caregivers of male and female patients responded in almost identical numbers (17 and 16, respectively). When patient/caregiver respondent was cross-referenced with seizure frequency, almost half (48.2%) of the patients who responded experienced six or fewer seizures per year, whereas almost half (45.4%) of the patients for whom caregivers responded experienced one or more seizures per week, with one-third (33.3%) experiencing more than one a day. Cross-referencing willingness to participate in clinical trials for implanted devices with seizure frequency revealed that 48.2% of the “no” (unwilling to participate) responses were from patients who have six or fewer seizures per year, whereas 22.3% of the “no” responses were for patients who have one or more seizures per day. Cross-referencing patient gender with willingness to participate in clinical trials for implanted devices showed that a larger percentage of male patients (44.0%) were open to participation in clinical trials for implanted devices than female patients (27.3%). 3.3. Seizure prediction and warning: Patients versus caregivers Caregivers of patients with epilepsy were specifically invited to participate in this survey and provide their opinions on seizure prediction and warning. Caregivers in many cases are integral to the treatment choices made for patients with epilepsy, and there may be value in examining their responses separate from and in comparison with patient responses. Both patients and caregivers expressed a strong desire for advanced warning of seizures, with 96.3% of patients and 93.8% of caregivers responding in the affirmative. In addition, 68.5% of patients placed a “high” or the “highest” value on warning for seizures whereas 79.4% of caregivers did so. As documented above and in Table 4, both patients and caregivers indicated that 3 to 5 minutes would be the best length of warning time of an impending seizure with the reasoning that this would allow enough time to take safety precautions and avoid embarrassment, but
Table 4 Cross-referencing of patient/caregiver respondent with preferred length of warning time. Preferred length of warning time
Number (%) Patients
Caregivers
b 1 min 1–3 min 3–5 min 5–10 min 10–25 min 25 min–1 h 1–6 h 6–12 h 12–24 h Other Total responses Unanswered
1 (1.9) 9 (16.7) 11 (20.4) 8 (14.8) 5 (9.3) 5 (9.3) 10 (18.5) 0 (0.0) 1 (1.9) 4 (7.4) 54 4
1 (3.2) 3 (9.7) 8 (25.8) 5 (16.1) 1 (3.2) 5 (16.1) 1 (3.2) 3 (9.7) 1 (3.2) 3 (9.7) 31
not so much time that it would be stressful and increase anxiety. However, nonparent family member caregivers preferred longer warning times of 25 minutes to 1 hour. The reasoning provided for this was “this would give the time needed to get someone to his home to care for him as he is having seizures.” A notable second choice for length of warning time for patients was 1 to 6 hours, and in addition to taking safety precautions, their comments indicated that this would help them “plan their day;” one even stated that it would allow me time to “drive myself to the hospital.” Responses from patients and caregivers differed markedly when asked if they wanted treatments triggered automatically by the prediction of seizures, with 90.3% of caregivers and 64.8% of patients indicating “yes.” Patients and caregivers were all strongly opposed to participation in clinical trials for implanted devices when provided only a categorical “yes” or “no” choice (67.3% “no” for patients and 63.3% “no” for caregivers). When given the opportunity to explain their answers in other questions on the survey, both groups showed reserved, cautious interest, wanting more information and assurances of efficacy. 4. Discussion Epilepsy, along with other neurological disorders and conditions such as Parkinson's, depression, and spasticity, is embracing advancements in technology and implantable devices for treatment [2–12]. The perspectives of patients and caregivers on the use of brain-implantable devices for the control of seizures, however, have not been formally determined and documented until recently [13,14]. We conducted a survey of patients and caregivers in the belief that the perspectives of patients with epilepsy and their caregivers need to be taken into account pari passu with the development of automated detection, prediction, and control of seizures to increase the likelihood of successful clinical application of new technologies to control seizures. A number of aspects of implantable devices and their impact remain to be understood by patients, caregivers, scientists, and clinicians, such as what is entailed in placement, maintenance, and retrieval, what are possible risks and side effects, and does stimulation have any unexpected consequences such as altered thinking and decision making [15]. Additional considerations are how safe devices are for children and whether they affect the maturation process. Notable for all researchers in seizure prediction is the preferred length of warning time (3–5 minutes) indicated by patients and caregivers in this survey. Longer warning times were seen as increasing stress and anxiety and, thus, decreasing quality of life. Shorter warning times would not provide adequate time for safety, comfort, or privacy and, thus, would be of little use. The nonparent caregivers chose considerably longer warning times (25 minutes to an hour) and explained that this was because they did not live with the patient so more time was needed to reach the patient. The distance in kinship appears to reflect a distance in location. A recent survey of German and Portuguese patients with epilepsy conducted by SchulzeBonhage et al. [14] examined the desirability of seizure prediction devices as well as the performance requirements of devices to make them acceptable to patients. That survey revealed a similar interest in predicting seizures and a similar preference for relatively short warning times. In that survey a preference was indicated for a seizure prediction window c 10 minutes in duration. The word that stood out prominently in this patient and caregiver survey was “fear.” Fear is ever present in the lives of patients with epilepsy and their caregivers. Quality of life is compromised by the constant fear of when the next seizure will occur, and fear is also the overriding cause for reservation about having devices implanted in the body. In addition, false predictions given by seizure prediction devices might not alleviate fear but could add to it. This problem was pointed out by Mormann et al. [16] and Schelter et al. [17], who used
S. Arthurs et al. / Epilepsy & Behavior 19 (2010) 474–477
periods under false warning as a criterion to judge the quality of seizure prediction algorithms. There is certainly reason for concern, and in the case of implantable devices, the concerns and fears may be overcome only by education and very complete and open discussions about foreseeable and unforeseeable risks. “No” was the very strong response to having devices implanted anywhere in the body. Investigators in academia and industry who are working on seizure prediction research must overcome the reluctance of respondents to embrace implantation of devices. This is a critical time in the development of seizure detection, prediction, and device-based control of seizures when opinions will be formed on safety, efficacy, and viability of implantable devices. The device industry in particular has a challenge in preparing their marketing approaches for any upcoming devices. In addition to the general aversion to invasive procedures, the considerable economic burden of epilepsy is of great concern [18], and the cost of implementing and maintaining seizure prediction devices will need to be considered and compared with the costs of the patient's current treatment. Also, will prediction devices totally eliminate the need for AEDs and/or other treatments? Or will they continue to be an additional expense albeit reduced? A careful evaluation of the total cost of diagnosis, surgeries, devices, and long-term follow-up care and demonstration that this is less than the current ongoing cost of pharmaceutical agents, doctor appointments, trips to the emergency room, injuries, and lost wages for caregivers may be important to convince patients and federal and private health insurers to embrace new therapeutic approaches that entail implantable devices. Underlying the comments from respondents was also a very strong sense of desperation and urgency. Current treatments leave many patients struggling and their caregivers shouldering continuous physical, financial, and emotional burdens. Many heart-wrenching comments were offered to researchers through the survey: “What are we waiting for?! Let's get a move on with this! This is very exciting!” “Act faster please!” “Please help my son's seizures. Keep him safe and give him a way to live a good quality of life. I want him to achieve all his goals without being denied a chance because of seizures.” “Thank you for trying; it would help so much to change her life even for a month.” The survey described here was not designed based on an a priori hypothesis, with a target sample size, or controlled for representative samples from all demographics. Rather this was an open survey of patients and caregivers conducted through the Internet for a fixed period (6 weeks). The information gathered though is undoubtedly important as it documents a thus far poorly evaluated but critical aspect of the development of brain-implantable devices for the control of seizures. We also note that quality-of-life issues for patients have changed little in the past 17 years since a Roper poll [1] was conducted on that topic. The same issues documented in the Roper poll are reflected throughout The Brainstorms Series [19], in which patients, caregivers, and family members tell their experiences of living with epilepsy. Automated seizure detection, prediction, and control hold a great deal of promise for long-awaited relief for patients and their caregivers.
477
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.yebeh.2010.
Acknowledgments We acknowledge Dr. Steven Schachter for helpful suggestions during the design of the survey, the Epilepsy Foundation of America (EFA) for publicizing the survey on their website, and the Alliance for Epilepsy Research for financial support.
References [1] Living with epilepsy: report of a Roper poll of patients on quality of life. New York: Roper Org., Inc.; 1992. [2] George R, Salinsky M, Kuzniecky R, et al. First International Vagus Nerve Stimulation Study Group. Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. Epilepsia 1994;35:637–43. [3] The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology 1995;45:224–30. [4] Salinsky MC, Uthman BM, Ristanovic RK, Wernicke JF, Tarver WB. for the Vagus Nerve Stimulation Study Group. Vagus nerve stimulation for the treatment of medically intractable seizures: results of a one-year open extension trial. Arch Neurol 1996;53:1176–80. [5] Osorio I, Frei MG, Sunderam S, et al. Automated seizure abatement in humans using electrical stimulation. Ann Neurol 2005;57:258–68. [6] Morrell MJ, the RNS™ System Pivotal Investigators. Results of a multicenter double blinded randomized controlled pivotal investigation of the RNS™ System for Treatment of Intractable Partial Epilepsy in Adults. Abstracts, Annual Meeting of the American Epilepsy Society (AES); December 2009. [7] Sun FT, Morrell MJ, Wharen Jr RE. Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics 2008;5:68–74. [8] Anderson WS, Kossoff EH, Bergey GK, Jallo GI. Implantation of a responsive neurostimulator device in patients with refractory epilepsy. Neurosurg Focus 2008;25:E12. [9] Smith JR, Fountas KN, Murro AM, et al. Closed-loop stimulation in the control of focal epilepsy of insular origin. Stereotact Funct Neurosurg 2010;88:281–7. [10] Stacey WC, Litt B. Technology insight: neuroengineering and epilepsy—designing devices for seizure control. Nat Clin Pract Neurol 2008;4:190–201. [11] Fisher RS, Handforth A. Reassessment: vagus nerve stimulation for epilepsy. Neurology 1999;53:666–9. [12] Fisher R, Salanova V, Witt T, et al, and the SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010;51:899–908. [13] Arthurs S. Patient perspectives: giving a voice to patients. Fourth International Workshop on Seizure Prediction; 2009. Available at: http://www.iwsp4.org/ program.htm. [14] Schulze-Bonhage A, Sales F, Wagner K, et al. Views of patients with epilepsy on seizure prediction devices. Epilepsy Behav 2010;18:388–96. [15] Frank MJ, Samanta J, Moustafa AA, Sherman SJ. Hold your horses: impulsivity, deep brain stimulation, and medication in Parkinsonism. Science 2007;318: 1309–12. [16] Mormann F, Elger CE, Lehnertz K. Seizure anticipation: from algorithms to clinical practice. Curr Opin Neurol 2006;19:187–93. [17] Schelter B, Winterhalder M, Feldwisch Genannt Drentrup H, et al. Seizure prediction: the impact of long prediction horizons. Epilepsy Res 2007;73:213–7. [18] Begley CE, Famulari M, Annegers JF, et al. The cost of epilepsy in the United States: an estimate from population-based clinical and survey data. Epilepsia 2000;41: 342–51. [19] Schachter SC. The brainstorms series. New York/London: Oxford Univ. Press; 2007.
Contents lists available at ScienceDirect
Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Patient and caregiver perspectives on seizure prediction Susan Arthurs a,⁎, Hitten P. Zaveri b, Mark G. Frei c, Ivan Osorio d a
Alliance for Epilepsy Research, P.O. Box 446, Dexter, MI 48130-0446, USA Department of Neurology, Yale University, New Haven, CT 06520, USA c Flint Hills Scientific LLC, 2513 Via Linda Drive, Lawrence, KS 66047, USA d University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA b
a r t i c l e
i n f o
Article history: Received 9 June 2010 Revised 5 August 2010 Accepted 9 August 2010 Available online 20 September 2010 Keywords: Seizure Epilepsy Patient with epilepsy Caregiver Patient survey Seizure prediction Implantable device
a b s t r a c t One of the goals of the Fourth International Workshop on Seizure Prediction was to provide an opportunity for patients with epilepsy and their caregivers to voice their perspectives on seizure prediction and related matters toward the goal of influencing the design of solutions. In an attempt to fulfill this goal, a survey of patients and caregivers, who often make or influence patient choices, was conducted on issues pertaining to living with epilepsy, epilepsy treatments, seizure prediction, and the use of implantable devices for the control of seizures. The results of this survey are reported here. © 2010 Elsevier Inc. All rights reserved.
1. Introduction It is estimated that as many as 60 million people in the world, and 3 million in the United States, have epilepsy. Furthermore, it was reported in a prior survey [1] that only 15% of the responding patients with epilepsy achieve full control of seizures without side effects through the use of antiepileptic drugs (AEDs). This lends support to the view that achieving full control of seizures without side effects through AEDs alone may be difficult, if not impossible, for many patients. Epilepsy affects millions more as family members and caregivers struggle to assist those with epilepsy endure this chronic disorder. An examination of the causes of disability, injury, and death in patients with medically intractable epilepsy finds seizure unpredictability to be the most crippling aspect and the one that negatively impacts safety, life span, and quality of life. The considerable progress in technology in the modern era has allowed researchers to expand their approaches to treating epilepsy from single-discipline pharmacological agents to multidiscipline efforts to detect or predict seizures and stop them with devices. The Fourth International Workshop on Seizure Prediction (IWSP4), an interdisciplinary meeting of investigators, was held June 4–7, 2009, in Kansas City, MO, USA, to discuss the status of the field of seizure
⁎ Corresponding author. P.O. Box 446, Dexter, MI 48130-0446, USA. Fax: + 1 734 4264877. E-mail address: [email protected] (S. Arthurs). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.08.010
prediction and related areas. One of the multiple goals of this workshop was to allow patients and their caregivers to provide their perspectives on seizure prediction toward the additional goal of influencing solutions. Patient and caregiver perspectives were determined by way of a survey. Caregivers were included in this survey because epilepsy impacts them as well as patients, and caregivers often influence the decisions of patients with epilepsy or make them on their behalf. This article reports the results of the survey of patients and caregivers on issues pertaining to living with epilepsy, treatments, and implantable devices for the control of seizures.
2. Methods A survey comprising 19 questions was designed and made available through a patient page on the IWSP4 website (http:// www.iwsp4.org). Three additional questions (zip code, numeric portion of street address or postal box number, and first name) were used to code individual submissions while protecting privacy; the zip code provided the geographic location of respondents, information that has some value in the interpretation of results. Respondents could complete and submit the survey online or could download, print, complete, and mail it. The survey was promoted both on the IWSP4 website and by the Epilepsy Foundation of America (EFA), which posted a news article on the EFA website with a link to the survey on the IWSP4 website. The survey was open for 6 weeks beginning April 1, 2009.
S. Arthurs et al. / Epilepsy & Behavior 19 (2010) 474–477
3. Results
475
Table 2 Side effects and problems reported from current treatments for epilepsy.
Eighty-nine responses were received, 84 through the Internet and 5 via mail. All responses were from the United States, with the zip codes being evenly distributed geographically from 01027 to 99703. Patients with epilepsy constituted 62.9% (56) of the respondents, parent caregivers 33.7% (30), and other family member caregivers 3.4% (3). There were no submissions from unrelated caregivers. Submissions for all patients aged 15 and younger (21) and an additional 11 responses were from caregivers. Survey questions are stated below and responses received are summarized. The survey and responses obtained are also fully documented in Tables S1–S22 (see Appendix A). Of the patients referenced in the submissions, 61 (68.5%) were female and 28 (31.5%) male. Patients ranged in age from 2 to 87 (Table S3 [see Appendix A]). Duration of epilepsy ranged from 0 to 72 years, with half reporting durations of 15 years or longer.
3.1. Seizure frequency, effects of current treatments, and burdens of epilepsy Survey question (select one answer): “Seizure frequency –.” In response to the survey question on seizure frequency, more than half of the patients (58.3%) reported experiencing one or more seizures per month (Table 1). Survey question (comment/essay answer): “What side effects or problems do you experience from epilepsy treatments?” Patients experienced a variety of side effects and problems from their epilepsy treatments (Table 2). Many respondents listed more than one side effect or problem, with the average being 2.5 problems per patient. The most commonly cited problems were tiredness and issues with memory. Fourteen respondents (15.9%) reported no problems. We note that some of these problems may have other causes, such as brain damage underlying the epilepsy or effects of interictal and ictal epileptic activity, and may not be due to the current treatment being received. Survey question (comment/essay answer): “Whether you are an epilepsy patient or caregiver, describe the effects of epilepsy and epilepsy treatments on your quality of life.” Epilepsy and treatments for epilepsy can have a major impact on the quality of life for both patients and caregivers (Table 3). Many respondents reported multiple issues with having epilepsy in their life. The average number of effects of epilepsy and epilepsy treatments on quality of life was 1.75. Survey question (comment/essay answer): “In your opinion, what is the most difficult part of having epilepsy?” The most difficult part of having epilepsy was fear for 42 respondents (48.3%); social issues for 38 (43.7%); medical issues for 15 (17.2%); inability to drive for 13 (14.9%); work problems for 7 (8.0%); and other for 6 (6.9%). Thirtytwo respondents (36.8%) had more than one “most” difficult issue. One respondent stated: “One of the worst things about seizures is that you don't know when one is coming. We live in a constant state of alert. It's hard to relax.”
Side effects
Number of patients
Tiredness Memory problems None Dizziness Mood problems Seizures continue Concentration issues Headaches Appetite Shaking Other side effects
31 15 14 9 9 8 7 7 6 6 b 6 each
3.2. Looking ahead to seizure warnings and implantable treatment devices Survey question (select yes or no): “Would you want advanced warnings of your seizures?” Eighty-four (95.5%) responded “yes.” In contrast, however, one parent caregiver noted, “Our son has hundreds of seizures a day; knowing when they come is not helpful.” Survey question (select one answer): “From 1 to 5, with 5 being the highest, what value do you place on the ability to predict or warn of seizures?” Forty-three respondents (48.3%) placed the highest value (5) on the ability to predict or warn of seizures. A high value was indicated by 25 (28.1%), medium value by 20 (22.5%), low value by 1 (1.1%), and lowest value by 4 (4.5%). Survey question (select yes or no): “Would you want treatment to be automatically triggered by the prediction of seizures?” Sixty-five respondents (74.7%) indicated interest in having treatment triggered automatically by seizure warnings. (Treatments might include electrical stimulation, drug injection, or cooling in the area of the brain where the seizures originate.) Survey question (select one answer): “If you were warned of seizures, what length of time would be best?” The preferred length of seizure warning time was 3 to 5 minutes. The reasons provided for this duration suggested that a prime concern of the respondents was safety. This preferred duration would allow patients to reach a safe place, obtain help, or remove themselves from potentially embarrassing situations. Longer durations were seen as being more stressful and, thus, having a negative impact on quality of life. Survey question (comment/essay answer): “What are your feelings about having a device implanted in your brain?” When given the opportunity to explain their response, both patients and caregivers qualified their answers: 37 (43.0%) thought it might be acceptable if it would work, 28 (32.6%) wanted more information, 10 (11.6%) indicated that it does not appeal to them at present. Only 8 (9.3%) categorically stated “no.” Survey question (comment/essay answer): “If you do not want to have a device implanted in your brain, please provide the reason.” Of the 46 respondents who were not sure about or not interested in having devices implanted in the brain, the vast majority (31, 67.4%) cited fear Table 3 Effect of epilepsy and current epilepsy treatments on quality of life.
Table 1 Frequency of seizures experienced by patients. Seizure frequency
Number (%) of patients
b 1/year 1–6/year 1/month 1 every other week 1/week 1/day N 1/day
18 19 14 7 10 2 19
(20.2) (21.3) (15.7) (7.9) (11.2) (2.2) (21.3)
Effect on quality of life
Number of respondents
Fear Inability to drive Social issues Work problems Depression Fatigue School issues Stressed Other effects
25 17 13 13 12 11 8 7 b7 each
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as the reason. Among the other 15 (32.6%), 7 (15.2%) wished to have more information; 3 (6.5%) found it not appealing at present; and 5 (10.9%) had other reservations. One respondent commented, “I don't want to take any chances of being worse than I already am.” Survey question (select yes or no): “Would you be willing to participate in clinical trials for implanted devices?” When asked to categorically state if they would be willing to participate in clinical trials for implanted devices, that is given only “yes” or “no” responses as options, 54 (65.9%) responded “no.” Further insight into the perspectives provided can be gained by cross-referencing the responses to survey questions. When patient gender was cross-referenced with patient/caregiver respondent, three and a half times as many female patients responded as male patients (44 vs 12, respectively), whereas caregivers of male and female patients responded in almost identical numbers (17 and 16, respectively). When patient/caregiver respondent was cross-referenced with seizure frequency, almost half (48.2%) of the patients who responded experienced six or fewer seizures per year, whereas almost half (45.4%) of the patients for whom caregivers responded experienced one or more seizures per week, with one-third (33.3%) experiencing more than one a day. Cross-referencing willingness to participate in clinical trials for implanted devices with seizure frequency revealed that 48.2% of the “no” (unwilling to participate) responses were from patients who have six or fewer seizures per year, whereas 22.3% of the “no” responses were for patients who have one or more seizures per day. Cross-referencing patient gender with willingness to participate in clinical trials for implanted devices showed that a larger percentage of male patients (44.0%) were open to participation in clinical trials for implanted devices than female patients (27.3%). 3.3. Seizure prediction and warning: Patients versus caregivers Caregivers of patients with epilepsy were specifically invited to participate in this survey and provide their opinions on seizure prediction and warning. Caregivers in many cases are integral to the treatment choices made for patients with epilepsy, and there may be value in examining their responses separate from and in comparison with patient responses. Both patients and caregivers expressed a strong desire for advanced warning of seizures, with 96.3% of patients and 93.8% of caregivers responding in the affirmative. In addition, 68.5% of patients placed a “high” or the “highest” value on warning for seizures whereas 79.4% of caregivers did so. As documented above and in Table 4, both patients and caregivers indicated that 3 to 5 minutes would be the best length of warning time of an impending seizure with the reasoning that this would allow enough time to take safety precautions and avoid embarrassment, but
Table 4 Cross-referencing of patient/caregiver respondent with preferred length of warning time. Preferred length of warning time
Number (%) Patients
Caregivers
b 1 min 1–3 min 3–5 min 5–10 min 10–25 min 25 min–1 h 1–6 h 6–12 h 12–24 h Other Total responses Unanswered
1 (1.9) 9 (16.7) 11 (20.4) 8 (14.8) 5 (9.3) 5 (9.3) 10 (18.5) 0 (0.0) 1 (1.9) 4 (7.4) 54 4
1 (3.2) 3 (9.7) 8 (25.8) 5 (16.1) 1 (3.2) 5 (16.1) 1 (3.2) 3 (9.7) 1 (3.2) 3 (9.7) 31
not so much time that it would be stressful and increase anxiety. However, nonparent family member caregivers preferred longer warning times of 25 minutes to 1 hour. The reasoning provided for this was “this would give the time needed to get someone to his home to care for him as he is having seizures.” A notable second choice for length of warning time for patients was 1 to 6 hours, and in addition to taking safety precautions, their comments indicated that this would help them “plan their day;” one even stated that it would allow me time to “drive myself to the hospital.” Responses from patients and caregivers differed markedly when asked if they wanted treatments triggered automatically by the prediction of seizures, with 90.3% of caregivers and 64.8% of patients indicating “yes.” Patients and caregivers were all strongly opposed to participation in clinical trials for implanted devices when provided only a categorical “yes” or “no” choice (67.3% “no” for patients and 63.3% “no” for caregivers). When given the opportunity to explain their answers in other questions on the survey, both groups showed reserved, cautious interest, wanting more information and assurances of efficacy. 4. Discussion Epilepsy, along with other neurological disorders and conditions such as Parkinson's, depression, and spasticity, is embracing advancements in technology and implantable devices for treatment [2–12]. The perspectives of patients and caregivers on the use of brain-implantable devices for the control of seizures, however, have not been formally determined and documented until recently [13,14]. We conducted a survey of patients and caregivers in the belief that the perspectives of patients with epilepsy and their caregivers need to be taken into account pari passu with the development of automated detection, prediction, and control of seizures to increase the likelihood of successful clinical application of new technologies to control seizures. A number of aspects of implantable devices and their impact remain to be understood by patients, caregivers, scientists, and clinicians, such as what is entailed in placement, maintenance, and retrieval, what are possible risks and side effects, and does stimulation have any unexpected consequences such as altered thinking and decision making [15]. Additional considerations are how safe devices are for children and whether they affect the maturation process. Notable for all researchers in seizure prediction is the preferred length of warning time (3–5 minutes) indicated by patients and caregivers in this survey. Longer warning times were seen as increasing stress and anxiety and, thus, decreasing quality of life. Shorter warning times would not provide adequate time for safety, comfort, or privacy and, thus, would be of little use. The nonparent caregivers chose considerably longer warning times (25 minutes to an hour) and explained that this was because they did not live with the patient so more time was needed to reach the patient. The distance in kinship appears to reflect a distance in location. A recent survey of German and Portuguese patients with epilepsy conducted by SchulzeBonhage et al. [14] examined the desirability of seizure prediction devices as well as the performance requirements of devices to make them acceptable to patients. That survey revealed a similar interest in predicting seizures and a similar preference for relatively short warning times. In that survey a preference was indicated for a seizure prediction window c 10 minutes in duration. The word that stood out prominently in this patient and caregiver survey was “fear.” Fear is ever present in the lives of patients with epilepsy and their caregivers. Quality of life is compromised by the constant fear of when the next seizure will occur, and fear is also the overriding cause for reservation about having devices implanted in the body. In addition, false predictions given by seizure prediction devices might not alleviate fear but could add to it. This problem was pointed out by Mormann et al. [16] and Schelter et al. [17], who used
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periods under false warning as a criterion to judge the quality of seizure prediction algorithms. There is certainly reason for concern, and in the case of implantable devices, the concerns and fears may be overcome only by education and very complete and open discussions about foreseeable and unforeseeable risks. “No” was the very strong response to having devices implanted anywhere in the body. Investigators in academia and industry who are working on seizure prediction research must overcome the reluctance of respondents to embrace implantation of devices. This is a critical time in the development of seizure detection, prediction, and device-based control of seizures when opinions will be formed on safety, efficacy, and viability of implantable devices. The device industry in particular has a challenge in preparing their marketing approaches for any upcoming devices. In addition to the general aversion to invasive procedures, the considerable economic burden of epilepsy is of great concern [18], and the cost of implementing and maintaining seizure prediction devices will need to be considered and compared with the costs of the patient's current treatment. Also, will prediction devices totally eliminate the need for AEDs and/or other treatments? Or will they continue to be an additional expense albeit reduced? A careful evaluation of the total cost of diagnosis, surgeries, devices, and long-term follow-up care and demonstration that this is less than the current ongoing cost of pharmaceutical agents, doctor appointments, trips to the emergency room, injuries, and lost wages for caregivers may be important to convince patients and federal and private health insurers to embrace new therapeutic approaches that entail implantable devices. Underlying the comments from respondents was also a very strong sense of desperation and urgency. Current treatments leave many patients struggling and their caregivers shouldering continuous physical, financial, and emotional burdens. Many heart-wrenching comments were offered to researchers through the survey: “What are we waiting for?! Let's get a move on with this! This is very exciting!” “Act faster please!” “Please help my son's seizures. Keep him safe and give him a way to live a good quality of life. I want him to achieve all his goals without being denied a chance because of seizures.” “Thank you for trying; it would help so much to change her life even for a month.” The survey described here was not designed based on an a priori hypothesis, with a target sample size, or controlled for representative samples from all demographics. Rather this was an open survey of patients and caregivers conducted through the Internet for a fixed period (6 weeks). The information gathered though is undoubtedly important as it documents a thus far poorly evaluated but critical aspect of the development of brain-implantable devices for the control of seizures. We also note that quality-of-life issues for patients have changed little in the past 17 years since a Roper poll [1] was conducted on that topic. The same issues documented in the Roper poll are reflected throughout The Brainstorms Series [19], in which patients, caregivers, and family members tell their experiences of living with epilepsy. Automated seizure detection, prediction, and control hold a great deal of promise for long-awaited relief for patients and their caregivers.
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Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.yebeh.2010.
Acknowledgments We acknowledge Dr. Steven Schachter for helpful suggestions during the design of the survey, the Epilepsy Foundation of America (EFA) for publicizing the survey on their website, and the Alliance for Epilepsy Research for financial support.
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