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ABSTRACT: An NINDS-sponsored conference in April of 2011 reviewed issues in epilepsy clinical trials. One goal was to clarify new electronic methods for recording seizure information and other data in clinical trials.
This selective literature review and compilation of expert opinion considers advantages and limitations of traditional paper-based seizure diaries in comparison to electronic diaries.
Seizure diaries are a type of patient-reported outcome. All seizure diaries depend first on accurate recognition and recording of seizures, which is a problem since about half of seizures recorded during video-EEG monitoring are not known to the patient. Reliability of recording is another key issue. Diaries may not be at hand after a seizure, lost or not brought to clinic visits. On-line electronic diaries have several potential advantages over paper diaries. Smartphones are increasingly accessible as data entry gateways. Data are not easily lost and are accessible from clinic. Entries can be time-stamped and provide immediate feedback, validation or reminders. Data can also can be graphed and pasted into an EMR. Disadvantages include need for digital sophistication, higher cost, increased setup time, and requiring attention to potential privacy issues. The Epilepsy Diary by epilepsy.com and Irody, Inc. has over 13,000 registrants and SeizureTracker over 10,000, and both are used for clinical and research purposes. Some studies have documented patient preference and increased compliance for electronic versus paper diaries. Seizure diaries can be challenging in the pediatric population. Children often have multiple seizure types and limited reporting of subjective symptoms. Multiple caregivers during the day require more training to produce reliable and consistent data. Diary-based observational studies have the advantages of low cost, allowing locus-of-control by the patient and testing in a "real-world" environment. Diary-based studies can also be useful as descriptive "snapshots" of a population. However, the type of information available is very different from that obtained by prospective controlled studies. The act of self-recording observations may itself influence the observation, for example, by causing the subject to attend more vigilantly to seizures after changing medication. Pivotal anti-seizure drug or device trials still mostly rely on paper-based seizure diaries. Industry is aware of the potential advantages of electronic diaries, particularly, the promise of real-time transmission of data, time-stamping of entries, reminders to subjects, and potentially automatic interfaces to other devices. However, until diaries are validated as research tools and the regulatory environment becomes clearer, adoption of new types of diaries as markers for a primary study outcome will be cautious.
Recommendations from the conference included: further studies of validity of epilepsy diaries and how they can be used to improve adherence; use and further development of core data sets, such as the one recently developed by NINDS; encouraging links of diaries to electronic sensors; development of diary privacy and legal policies; examination of special pediatric diary issues; development of principles for observational research from diaries; and work with the FDA to make electronic diaries more useful in industry-sponsored clinical trials.
Epilepsy & Behavior 05/2012; 24(3):304-10. · 2.34 Impact Factor
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John F Kerrigan,
Brian Litt, Robert S Fisher,
Stephen Cranstoun,
Jacqueline A French,
David E Blum,
Marc Dichter,
Andrew Shetter,
Gordon Baltuch,
Jurg Jaggi,
Selma Krone,
MaryAnn Brodie,
Mark Rise,
Nina Graves
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ABSTRACT: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open-label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data.
We report an open-label pilot study of intermittent electrical stimulation of the anterior nucleus of the thalamus in five patients (three men, two women; age range, 24-47 years), with follow-up between 6 and 36 months. All patients had intractable partial epilepsy. Four of the five patients also had secondarily generalized seizures. Stimulation was delivered by bilateral implantable, programmable devices by using an intermittent, relatively high-frequency protocol. Stimulation parameters were 100 cycles per second with charge-balanced alternating current; pulse width, 90 ms; and voltages ranging between 1.0 and 10.0 V. Seizure counts were monitored and compared with preimplantation baseline.
Four of the five patients showed clinically and statistically significant improvement with respect to the severity of their seizures, specifically with respect to the frequency of secondarily generalized tonic-clonic seizures and complex partial seizures associated with falls. One patient showed a statistically significant reduction in total seizure frequency. No adverse events could clearly be attributed to stimulation. None of the patients could determine whether the stimulator was on or off at these parameters.
Electrical stimulation of the ANT appears to be well tolerated. Preliminary evidence suggests clinical improvement in seizure control in this small group of intractable patients. Further controlled study of deep brain stimulation of the anterior nucleus is warranted.
Epilepsia 05/2004; 45(4):346-54. · 3.96 Impact Factor
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ABSTRACT: We performed a pilot 3-month, open-label study of 5–10 mg donepezil, an anticholinesterase inhibitor, as treatment for memory problems in people with epilepsy. The Buschke Selective Reminding Test was administered at baseline and after 3 months of donepezil. In 18 completing patients, the total number of words recalled across learning trials was greater on donepezil (P = 0.4). No change was noted in attention, visual sequencing, mental flexibility, psychomotor speed, or reported quality-of-life scores. Mean 3-month seizure frequency at baseline was 2.70 ± 4.60, and during treatment, 3.06 ± 4.52 (P = 0.19, not significant). Two patients experienced increased tonic–clonic seizures. Side effects included diarrhea, stomach cramps, insomnia, depression, and blurred vision. Cholinergic medication is worthy of investigation as treatment for memory problems in people with epilepsy, but attention must be paid to possible exacerbation of seizures.
Epilepsy & Behavior 09/2001; · 2.34 Impact Factor
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ABSTRACT: Oxcarbazepine (OXC) is a keto analogue of carbamazepine with no epoxide metabolite. We performed an open-label pilot study of OXC in six men and four women undergoing presurgical evaluation for complex partial or secondarily generalized seizures. Mean age was 34.3 ± 8.3 years, and mean duration of epilepsy was 18.2 ± 11.1 years. Patients were monitored for approximately 7 days before entry into an open-label add-on OXC study. Baseline antiepileptic medications were stopped in seven of the ten patients prior to initiating OXC. OXC was titrated to 2,400 mg/day in two divided doses over 2–3 days. The baseline daily seizure frequency was 0.75 ± 0.49, compared to 0.19 ± 0.31 seizures per day during the 10 days subjects were on OXC (P = .04, two-tailed paired t test). Overall, 80% of patients showed at least a 50% reduction in seizures, and the mean reduction was to 32% of the baseline. Adverse events consisted of nausea (20%), ataxia (10%), fatigue (10%), blurred vision (10%), and pruritus (10%). Segmented neutrophil counts, serum sodium, and serum AST declined with OXC. This pilot study suggests preliminary evidence for safety and efficacy of OXC. © 1996 Wiley-Liss, Inc.
Drug Development Research 12/1998; 38(1):43 - 49. · 1.19 Impact Factor
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ABSTRACT: Purpose: Positron emission tomography (PET) has proven useful in epilepsy surgery for its ability to identify unilateral temporal hypometabolism (UTH), which is predictive of good surgical outcome. The significance of bilateral temporal hypometabolism (BTH) is not known.Methods: We identified all patients who had marked bilateral reduction in temporal lobe metabolism relative to the cerebellar hemispheres and compared their clinical features and treatment outcomes with those of control patients with UTH.Results: BTH was evident in 10% of PET scans for epilepsy at our institution. We compared these patients with age-matched controls with UTH. The BTH patients had a higher percentage of generalized seizures; were more likely to have bilateral, diffuse or extratemporal seizure onsets; and had bilateral or diffuse magnetic resonance imaging (MRI) findings. UTH patients were more likely to have unilateral mesial temporal atrophy on MFU. Even when electrical seizure onsets were well localized, surgical outcomes were markedly worse in these patients than in controls. Medical treatment was also less successful. Social and cognitive functioning was worse in the BTH group. The only death occurred in the group with BTH.Conclusions: Patients with BTH have features distinct from those with UTH and have a worse prognosis for seizure remission after surgery.
Epilepsia 05/1998; 39(6):651 - 659. · 3.96 Impact Factor
