This year's American Academy of Neurology Annual Meeting in San Diego, California, featured more than 1400 scientific presentations, with well over 100 illustrating advances in epilepsy research. (Attendees were spared the temptation of the beaches by the unseasonably cool and wet weather.) The abstract and platform sessions included updates on long-term results with the ketogenic diet, predictors of employment after epilepsy surgery, epilepsy and hepatitis C, epilepsy surgery in children, valproate and weight gain in children, epilepsy in women, and the relationship between sleep apnea, epilepsy, and quality of life. Brief summaries of these presentations are presented below.
Perhaps fueled by enthusiasm for more "natural" therapies, there has been a resurgence of interest in the ketogenic diet, an epilepsy treatment that has been available for more than 75 years. Other diets also being explored for the treatment of epilepsy include the medium-chain triglyceride, Atkins, and South Beach diets. Efficacy and adverse events of these diets for people with epilepsy have not yet been fully characterized.
A retrospective study from Johns Hopkins Medical Center, Baltimore, Maryland, a long-standing proponent of the ketogenic diet, reported the results of 28 children who had stayed on the ketogenic diet for 6-12 years (mean, 7.8 years).[1] Three patients achieved seizure freedom; 21 (75%) had greater than a 90% decline in seizure frequency; and 4 (14%) had a 50% to 90% decline in seizure frequency. Nine patients (33%) discontinued all antiepileptic drugs. The average number of antiepileptic drugs decreased from 2.1 to 1.3 (P = .003). Nearly all (98%) of the families were either "satisfied" or "highly satisfied" with the diet.
Darcy Groesbeck, a third-year medical student who presented the research, observed, "If you put kids on the diet, efficacy can be maintained for a long time. A lot of tweaking, especially in the early stages, may be necessary to make the diet work."
Adverse events included kidney stones in 7 (25%) children, bone fractures in 6 (21%), and delayed growth. At baseline, 50% of the children were less than the 10th percentile for weight, which increased to 82% at the most recent follow-up (P = .01). Similarly, at baseline, 36% of children were less than the 10th percentile for height, which increased to 82% at the most recent follow-up (P = .0004).
Ms. Groesbeck advised, "We haven't routinely been getting DEXA scans, but we should consider long-term bone density monitoring. Children should be seen every 6-12 months for laboratory work and clinical follow-up."
"The best predictor for gainful employment postsurgically is to have been working before surgery," reported Andres M. Kanner, MD, Professor of Neurological Sciences, Rush Medical College, Chicago, Illinois.
Dr. Kanner and his colleagues Marlis Frey, RN, a nurse practitioner, and Richard Byrne, MD, a neurosurgeon, reviewed the employment records of 88 consecutive adults (57 men, 31 women; mean age, 30.7) who had a left (N = 47) or right (N = 41) temporal lobectomy for intractable epilepsy (mean duration, 19.7 years).[2] Patients were followed after surgery for a mean of 6.9 years. On multivariate analysis, presurgical employment (P = .001) and lack of disabling seizures (IA-IB) (P = .023) were correlated with gainful employment. Two variables had a negative correlation with employment: presurgical depression (P = .024) and severe postoperative psychopathology (P = .02). In addition, a presurgical history of depression was a strong predictor of postsurgical psychiatric complications (P < .0001).
Dr. Kanner recommended, "Patients with epilepsy who are not working at the time of an initial epilepsy evaluation should undergo a vocational evaluation and be referred to vocational rehabilitation programs whereafter being trained they are assisted in getting gainful employment."
"Chronic hepatitis C does not seem to be a risk for seizures," observed Anne Mai, MD, an epilepsy fellow at the Comprehensive Epilepsy Center, Mayo Clinic, Phoenix, Arizona. Dr. Mai and her colleagues[3] performed a retrospective analysis of 1482 patients with hepatitis C virus between 1998 and 2005 who were included in the Mayo Clinic Arizona database. Only 12 patients (0.81%; 6 men, 6 women; age, 43-62) had epilepsy, which is consistent with the expected prevalence of epilepsy in the general population. Head trauma was the likely etiology of seizures in 75% of the people with epilepsy. Two thirds of the patients were controlled with monotherapy. Gabapentin and levetiracetam were the most frequently used antiepileptic drugs.
Seizure control and general well-being improve after successful epilepsy surgery in children, but psychosocial and behavioral function lag behind, according to a presentation by Mohamad Mikati, MD, and colleagues[4] at the American University of Beirut Medical Center, Beirut, Lebanon.
Dr. Mikati, Director, Adult and Pediatric Epilepsy Program, compared a cohort of children ages 4-18 years who had frontal and temporal lobe resections for intractable epilepsy (N = 17) with a cohort of similar children who had not yet had the surgery (N = 12). The groups were matched for age, sex, socioeconomic status, seizure and epilepsy type, seizure frequency, duration, age of onset and duration of epilepsy, and number of medications. The mean follow-up after surgery was 28.9 months. As expected, patients in the surgery group were more likely to be seizure-free (P = .01) and to be on less than 3 antiepileptic drugs (P < .01). Patients in the surgery group had significantly better scores on the Hague Seizure Severity Scale (HASSS) (P = .03), the Hague Side Effects Scale (HASES) (P = .00), and the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE) (P = .01). Within the quality-of-life measure, patients in the surgical group scored higher on physical activities (P = .03), general health (P = .00), and overall quality of life (P = .038). However, behavior, cognitive functioning, social activities, and well-being scores were not statistically different from the control group.
Dr. Mikati observed:
There is a discrepancy between what the patient can do and how the patient is functioning. We believe that these results are very related to the parents' attitude regarding their children. Parents were still worried, even though the child is seizure-free. They still spoil the child, and all of this affects the intellectual and social functioning of the child. It is important to counsel the patients so that they can achieve better quality of life.
Dr. Mikati plans to increase the number of patients in the study and look for potential differences between children and adolescents.
Children less than 12 years old did not gain weight while taking valproate, according to a retrospective chart review of 35 children on valproate (mean age, 9.3) and 49 children on carbamazepine (mean age, 7.15), presented by Patricio Espinosa, MD, MPH, a third-year neurology resident at the University of Kentucky College of Medicine and Public Health, Lexington, Kentucky.[5] The valproate group included 77.4% males. Their mean weight was 15.9 kg, and they were followed for 37 months. The carbamazepine group included 40.8% males. Their mean weight was 12.2 kg, and they were followed for 45 months. A linear mixed model did not detect a gain in body mass index z scores over time for valproate (P = .80), but did detect a gain for carbamazepine (P = .02). The McNemar chi-square test did not show weight gain in the valproate group (P = .15), but did reveal a significant increase in the proportion of overweight children on carbamazepine (P = .03). Limitations of the study include a relatively small number of patients overall, as well as lack of matching between groups with regard to baseline age, sex, weight, and duration of follow-up.
Dr. Espinosa observed, "These findings suggest that results from adults and adolescents cannot be routinely extrapolated to infants and children."
Andrew Herzog, MD, Director of the Neuroendocrine Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, reported baseline data from the first 100 women to enter a multicenter investigation of supplemental progesterone therapy for intractable epilepsy.[6] Baseline data revealed 2 important findings: Seizure frequency is increased by 28% when women don't ovulate (P = .08), and anovulation is more common when the menstrual cycle is shorter than 26 days or longer than 30 days.
Dr. Herzog observed:
There is very much a reciprocal relationship between seizures and hormones. The temporolimbic system, which is the site of origin for most adult epilepsy, has massive direct connections to the hypothalamus, which regulates the pituitary, which regulates the ovary. Anovulatory cycles feature estrogen without progesterone, and estrogen is epileptogenic. Failure of ovulation and the hormonal changes that accompany it (unopposed estrogen) may be associated with more seizures.
Symptoms of sleep apnea may be missed by the Quality of Life in Epilepsy (QOLIE-89) inventory, according to a study presented by Bradley Vaughn, MD, Professor of Neurology, Division of Sleep Disorders and Epilepsy, University of North Carolina at Chapel Hill.
Dr. Vaughn and colleagues[7] participated in a multicenter, double-blind, controlled study of continuous positive airway pressure that included 35 adult inpatients (18 men, 17 women; mean age, 40.1) with intractable epilepsy and symptoms of snoring to determine whether continuous positive airway pressure treatment of obstructive sleep apnea improves seizure frequency and quality of life. Subjects had an average body mass index of 32 (20.8-60.7), seizure frequency of 19.7/month (range, 1-110), and took an average of 2.1 antiepileptic drugs (range, 1-4). On polysomnography, the average apnea-hypopnea index was 14.1 events per hour, with average lowest oxygen desaturation 84.5%.
The average QOLIE score was 57.3 (29.94-89.97). The QOLIE did not correlate significantly with the percentage of total sleep time, sleep stages, or rates of apneas and hypopneas per hour. However, health perception did negatively correlate with time (P = .024) and percentage in stage I sleep (P = .023).
Dr. Vaughn observed:
These results suggest 1 or more of the following 3 explanations: (1) The QOLIE-89 is the wrong tool to detect obstructive sleep apnea; (2) it may be that obstructive sleep apnea has little impact on individuals with epilepsy; (3) individuals with epilepsy don't recognize the impact of obstructive sleep apnea because they have so many other issues.
Dr. Vaughn added, "To differentiate these explanations, we will need to evaluate patients using other quality-of-life scores, categorize the patients into potential pathophysiological mechanisms driving the obstructive sleep apnea, and repeat these measures following adequate treatment of the obstructive sleep apnea."
Beth Malow, MD, a coauthor of the study, concluded:
Quality of life is a real important issue in epilepsy, and we want to make sure the measures we are using are sensitive to sleep problems. The QOLIE-89 does address energy and fatigue, but not sleep per se. When we develop quality-of-life scales for epilepsy, we need to include specific questions about sleep. Clinicians should be aware that the QOLIE-89 may not be a sensitive tool for detecting obstructive sleep apnea.
This brief review of selected presentations from the American Academy of Neurology's 58th Annual Meeting hints at the wide breadth of topics covered and the increasing depth of the research studies. For example, data in regard to long-term success of the ketogenic diet is helping to propel the diet from an "alternative" approach to a well-studied mainstream treatment for epilepsy. With respect to epilepsy surgery in children, the question is no longer whether surgery is appropriate, but how we can intervene to maximize its psychosocial benefit. Dr. Herzog's report on women and epilepsy continues to lay a foundation for understanding the complex interactions between hormones and seizures. Dr. Vaughn's study seeks to establish whether symptoms of sleep apnea, which are increasingly recognized as important to people with epilepsy, are detected by the QOLIE inventory. With these studies as groundwork, one may expect that next year's presentations will advance our knowledge even further, leading to improved outcomes for people with epilepsy.