Treatment Of Seizure Disorders Research Articles

Perampanel for the Control of Drug-Resistant Partial-Onset Seizures in Patients 12 years and Older

Recent developments in the treatment of seizure disorders have been focused on medications with novel mechanisms of action. One such medication is perampanel, a first-in-class, noncompetitive, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist recently approved for the adjunctive treatment of partial seizures in patients 12 years of age and older when other antiepileptic medications have failed. The drug has demonstrated efficacy in several clinical trials, and appears to exert its anti-seizure activity in a dose-dependent manner. The drug has a half-life of approximately 105 hours suggesting the medication might be a logical option for individuals who have difficulty with adherence to medications that require multiple daily doses. Because of changes in serum concentration when enzyme-inducing antiepileptic drugs are employed concurrently, escalations in the initial dose of perampanel are recommended. Adverse events reported with perampanel use tend to be mild to moderate. However, psychiatric side-effects, including hostility and aggressive behavior, have been noted in some patients resulting in the inclusion of a warning on the Food and Drug Administration (FDA) approved labeling.

Histone deacetylase inhibitor, valproic acid, radiosensitizes the C6 glioma cell line in vitro

Valproic acid (VPA) is a well-tolerated drug that is used to treat seizure disorders and that has recently been shown to inhibit histone deacetylase. The present study investigated the effects of VPA on the radiosensitization of the rat C6 glioma cell line in vitro. To select an appropriate treatment concentration and time, MTT and flow cytometry assays were performed to measure the inhibitory effects of VPA at various concentrations and incubation time-points. The radiosensitizing effect of VPA was determined using clonogenic experiments. VPA- and radiation-induced C6 apoptosis was analyzed using quantitative polymerase chain reaction and western blot analysis. Cell proliferation was significantly inhibited by VPA in a time- and dose-dependent manner (P<0.05). VPA enhanced radiation-induced C6 cell death and there was clear inhibition of clonogenic formation [sensitizer enhancement ratio (SER), 1.30]. This effect was closely associated with the concentration of VPA. VPA treatment decreased the mRNA and protein levels of Bcl-2, whereas increased changes were detected with Bax. At a concentration of 0.5 mmol/l, VPA had a low toxicity and enhanced the radiosensitization of the C6 cells. VPA may radiosensitize glioma cells by inhibiting cellular proliferation and inducing apoptosis by regulating apoptosis-related molecular changes.

Phenytoin Loading Doses in Adult Critical Care Patients: Does Current Practice Achieve Adequate Drug Levels?

Phenytoin is regularly employed in the critically ill for prophylaxis against or treatment of seizure disorders. No prior studies have examined current dosing practices in an Australasian intensive care unit (ICU) setting. The aims of this study were to: a) describe the adequacy of contemporary dosing in respect to free and total serum phenytoin concentrations; b) identify factors associated with therapeutic drug concentrations; and c) examine the accuracy of predictive equations that estimate free concentrations in this setting. All patients receiving a loading dose of phenytoin in a tertiary-level ICU were eligible for enrolment; 53 patients were enrolled in the study. Serum samples to determine free and total phenytoin concentrations (measured by high performance liquid chromatography) were then drawn prior to the following dose. Free concentrations below the recommended target (<1 mg/l) were considered as suboptimal. The most common indication for phenytoin loading was traumatic brain injury (49%) and the mean administered dose was 14.5 (3.66) mg/kg. Twenty-six patients (49%) had suboptimal trough free concentrations, although this subgroup was significantly heavier and therefore received a lower per kilogram dose (12.8 [3.1] vs 16.3 [3.4] mg/kg, P=0.001). In multivariate analysis, larger weight adjusted doses (P=0.018), higher albumin concentration (P=0.034) and receiving phenytoin for an indication other than seizure (P=0.035), were associated with a greater likelihood of adequate concentrations. In conclusion, phenytoin dosing remains complex in critically ill patients, although lower per kilogram loading doses are strongly associated with free concentrations below the desired target.

Valproic acid inhibits cell size and cell proliferation by AMPK-mediated mTOR signaling pathway in JEG-3 cells

Valproic acid is commonly used to treat seizure disorders, bipolar disorder, migraine prophylaxis, and neuropathic pain. Despite its effectiveness and widespread use, valproic acid has been proven to exert considerable teratogenic potential, such as neural tube defects and malformations of the heart in both the humans and animals. However, the molecular mechanism of the teratogenic effects of valproic acid has not been fully elucidated. Because adverse effects in fetus by teratogens are obviously detectable only after birth and there are the limits of teratogenicity testing using rodents, such as thalidomide tragedy, new strategies for pre-determining teratogenic effects are required. Here, we try to elucidate the indirect teratogenicity of valproic acid in a human placenta-derived cell line (JEG-3) using a transcriptomic approach. In this study, using human whole genome oligonucleotide microarray, we identified 2,076 up- and 1,730 down-regulated genes which were changed more than 1.5-fold in JEG-3 cells exposed to valproic acid. Many of these genes have associations with lysosome, transport, tight junction, splicesome, cell cycle and mammalian target of rapamycin (mTOR)-signaling pathway. Among these, we focused on the adenosine monophosphate (AMP)-dependent kinase or AMP-activated kinase (AMPK)-mediated mTOR signaling pathway, and hypothesized that the negative control of mTOR signaling by AMPK might induce inhibition of the growth of JEG-3 cell exposed to valproic acid. First, flow cytometry analysis showed that valproic acid induced the inhibition of cell growth caused by G1 phase arrest. Second, the expression of genes related to mTOR signaling was changed. Using quantitative real-time RT-PCR data, it was confirmed that PTEN, PIK3CB, PIK3CD, PIK3R3, IRS2, and PRKAA2 (AMPKα2) were overexpressed, and that GβL and AKT1 were under-expressed in valproic acid treated JEG-3 cells compared to a control. We also confirmed the protein expression and the activation of AMPK and raptor after valproic acid exposure. Thus, this study suggests that valproic acid affects AMPK, and then AMPK may influence cell growth through mTOR signaling, and particularly, mTOR activity is suppressed by raptor activation. From this point of view, these genes may provide potential biomarkers that may contribute to decrease the number of candidate drugs showing teratogenicity in large-scale tests using placenta cells.

Immunological Variations in Epileptic Children

Epilepsy is one of the most frequent neurological problems. Despite of the advances and improvements in treatment of seizure disorders, immunological alterations such as immunoglobulins and complements have been measured. The levels of IgG in epileptic patients are found to be higher than controls. The levels of IgA, IgM, C3 and C4 were found to be lower in all the controls. Student’s t-test were also applied. Multiple and regression analysis, have been also carried out. A trend has also set up in the present study. An alteration in the immune mechanism of epileptic patients is required. Ketogenic diet may be given and the balance of trace elements like Na, K, Zn, Fe, Ca, Mg and Cu may be maintained to alter the immune mechanism of the epileptic patients. Green leafy vegetables may be given to the patients to control the seizure. Immunity is related with the food we eat. By adjusting the immunity with proper diet the severity of epileptic attack or any disease may be reduced.

Pediatric News

Pediatric News

Scalar Field Therapy and Mitigation of Seizure Disorder: A Case Report

This case report describes the use of scalar field therapy in the mitigation of seizures in an autistic child. The patient is a 4-yr-10-mo-old girl with a 3 year history of seizure disorder and autism. She presents with a long history of a series of 6 to 8 tonic-clonic seizures on a daily basis, each lasting approximately 10 to 20 seconds long. After a series of treatments in the scalar field, her seizures were reduced to 4 to 5 partial seizures of just 1 to 2 seconds in duration. The reduction in number and duration of seizures in this case suggests that the use of scalar field therapy in the treatment of seizure disorder should be further explored. Of great importance is the potential for controlling seizures while minimizing the use of pharmaceuticals that are often debilitating and have numerous negative side effects. doi: http://dx.doi.org/10.4021/jnr134w

Identification of tiagabine degradation products using liquid chromatography with electrospray ionization multistage mass spectrometry and ultra‐performance liquid chromatography/high‐resolution mass spectrometry

Tiagabine hydrochloride monohydrate drug substance (TGB) is an antiepileptic agent effective in the treatment of seizure disorders. The stability of TGB was studied and its degradation products were identified for the first time. TGB was heated in the presence of H(2)O(2). Degradation products were analyzed by liquid chromatography coupled to electrospray ionization multistage mass spectrometry (LC/ESI-MS(n)) and high-resolution mass spectrometry (HR-MS). This study showed that TGB was degraded by oxidative pathways involving attack of oxygen at different centers but mainly at the double bond of the molecule. The oxidative cascade reactions initiated by the epoxidation of the double bond of tiagabine led to dihydroxy, ketohydroxy and ketone derivatives as well as bisthiophene ketone. Nine degradation products of TGB were identified. Some diagnostic MS/MS product ions, characteristic of the piperidine or thiophene moiety, were highlighted.

Scalar Field Therapy and Mitigation of Seizure Disorder: A Case Report

This case report describes the use of scalar field therapy in the mitigation of seizures in an autistic child. The patient is a 4-yr-10-mo-old girl with a 3 year history of seizure disorder and autism. She presents with a long history of a series of 6 to 8 tonic-clonic seizures on a daily basis, each lasting approximately 10 to 20 seconds long. After a series of treatments in the scalar field, her seizures were reduced to 4 to 5 partial seizures of just 1 to 2 seconds in duration. The reduction in number and duration of seizures in this case suggests that the use of scalar field therapy in the treatment of seizure disorder should be further explored. Of great importance is the potential for controlling seizures while minimizing the use of pharmaceuticals that are often debilitating and have numerous negative side effects. J Neurol Res. 2012;2(4):172-175 doi: https://doi.org/10.4021/jnr134w

Effect of valproic acid on the outcome of glioblastoma multiforme

Background. Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor. It is a rapidly progressive, highly recurrent, fatal intracranial neoplasm, and the demand for novel treatment is urgent. Valproic acid (VPA) is a potential anticancer agent that belongs to a class of histone deacetylase (HDAC) inhibitors, targeting the epigenetic control of gene functions in cancer cells. This drug has been administered for the prevention or treatment of seizure disorder in GBM patients; therefore, a retrospective analysis may further our understanding of the effect of VPA on GBM patients. Materials and methods. A retrospective analysis of 102 patients with GBM was conducted to study the effects of VPA on disease outcome. Tumor samples from seven patients receiving VPA treatment between the first and second operations were obtained in order to verify the HDAC inhibitory activity of VPA in these patients. Results. In univariate analysis, administration of VPA within 2 weeks of initial diagnosis seemed to confer a survival benefit. However, stratified analysis according to chemotherapy showed that VPA did not have significant impact on the GBM patients’ overall survival. Analysis of tissue samples from these patients revealed that a small subset of patients had increased histone acetylation after VPA treatment. Conclusion. VPA treatment, when administered according to a protocol targeting seizure control, may result in HDAC inhibition in a small subset of patients, but does not significantly affect overall patient survival. Early administration of VPA as an adjunct to temozolomide chemotherapy may have its merits, but the optimal dosing schedule and target serum level require further investigation.

Case Report of Valproate-Induced Hypothermia in a Patient With Schizoaffective Disorder

Case Report of Valproate-Induced Hypothermia in a Patient With Schizoaffective Disorder

Veterinarians' preferences for anticonvulsant drugs for treating seizure disorders in dogs and cats

To identify veterinarians' approaches and concerns when managing canine and feline patients with acute and chronic seizure disorders. Cross-sectional survey. A questionnaire was distributed to veterinarians to determine how many dogs and cats they were actively treating for seizures, their anticonvulsant drug (ACD) preferences for treating acute and chronic seizure disorders and whether serum anticonvulsant concentrations and/or biochemical analytes were routinely measured. Additional questions involved the respondent's year and place of graduation and identified concerns they faced when managing patients with seizure disorders. Phenobarbitone was the most commonly used ACD for managing chronic seizure disorders in both dogs and cats, with 82% of respondents using a combination of phenobarbitone and potassium bromide to manage refractory seizure disorders in dogs. Most respondents (96%) felt comfortable managing seizures in dogs, but only 63% were comfortable managing affected cats. Routine monitoring of serum ACD concentrations and of liver biochemical analytes was performed routinely by 71% and 45% of respondents, respectively. Of the respondents, 86% graduated from Australian universities and of these 53% had graduated after 1985. Veterinarians identified when to commence medication, whether regular monitoring of serum ACD concentrations and liver enzyme activity was necessary, and if the cost was justified. Veterinarians also identified the need to balance dose rates and side-effects by using combination therapy, and the importance of providing accurate information to clients about what to expect in terms of seizure control for their pet.

The cortical innate immune response increases local neuronal excitability leading to seizures

Brain glial cells, five times more prevalent than neurons, have recently received attention for their potential involvement in epileptic seizures. Microglia and astrocytes, associated with inflammatory innate immune responses, are responsible for surveillance of brain damage that frequently results in seizures. Thus, an intriguing suggestion has been put forward that seizures may be facilitated and perhaps triggered by brain immune responses. Indeed, recent evidence strongly implicates innate immune responses in lowering seizure threshold in experimental models of epilepsy, yet, there is no proof that they can play an independent role in initiating seizures in vivo. Here, we show that cortical innate immune responses alone produce profound increases of brain excitability resulting in focal seizures. We found that cortical application of lipopolysaccharide, binding to toll-like receptor 4 (TLR4), triples evoked field potential amplitudes and produces focal epileptiform discharges. These effects are prevented by pre-application of interleukin-1 receptor antagonist. Our results demonstrate how the innate immune response may participate in acute seizures, increasing neuronal excitability through interleukin-1 release in response to TLR4 detection of the danger signals associated with infections of the central nervous system and with brain injury. These results suggest an important role of innate immunity in epileptogenesis and focus on glial inhibition, through pharmacological blockade of TLR4 and the pro-inflammatory mediators released by activated glia, in the study and treatment of seizure disorders in humans.

Topiramate for Use in Adult Migraine Prophylaxis

Objective: To review studies comparing topiramate with placebo or other migraine prophylaxis agents in order to outline the role of topiramate in the pharmacologic prevention of adult migraine and to provide clinicians with evidence for rationale of its use. Data Sources: Primary studies and review articles were identified via a MEDLINE search (1960–November 2008). Search terms included topiramate, antiepileptic, anticonvulsant, migraine prophylaxis, and migraine prevention. Additional references were obtained from bibliographies of those resources. Study Selection and Data Extraction: All relevant information extracted from randomized, controlled studies and systematic reviews evaluating the efficacy, safety, and pharmacology of topiramate in the prevention of adult migraine were included. Data Synthesis: Topiramate is approved for the prevention of adult migraine. It has historically been used in the treatment of seizure disorders but received approval for migraine prophylaxis in 2004. The exact mechanism of its antimigraine effect remains unknown, but modulation of sodium channels, γ-aminobutyric acid, and glutamate activity seem to be involved, given the proposed shared pathophysiology between seizure and migraine. Two pivotal trials comparing topiramate with placebo led to approval for migraine prophylaxis in the US and a third similar trial that compared topiramate with propranolol secured licensure in Europe. Additional studies evaluated optimal dosing up to 200 mg daily and duration of therapy through 14 months. These trials demonstrated the ability of topiramate 50 mg twice daily, administered for up to 14 months, to safely reduce migraine frequency, duration, and severity. Limited information from comparative studies suggests a similar effect of topiramate and other agents, including divalproex sodium, propranolol, and timolol. The most common adverse effect observed among all trials was mild-to-moderate paresthesias that were transient in nature. Other adverse effects commonly reported include gastrointestinal upset and cognitive impairment. Adverse effects were more likely to occur during titration periods. Topiramate's safety profile appears to be as good as or better than that of other prophylactic agents. Conclusions: Topiramate is an appropriate first-line drug to consider for prevention of adult migraine. The efficacy and safety of topiramate in migraine prophylaxis has been well established in clinical trials and is comparable with other approved agents for this indication. When choosing among these agents, prescribers should consider the adverse effect profile, route of administration, cost, and comorbidities. ACPE Universal Program Number: 407-000-09-052-H01-P (Pharmacists); 407-000-09-052-H01-T (Technicians)

Electroencephalographic and behavioral convulsant effects of hydrobromide and hydrochloride salts of bupropion in conscious rodents.

A novel bromide salt of the antidepressant bupropion (bupropion HBr) has recently been developed and approved for use in the United States. Given previous use of bromides to treat seizures, and that the existing chloride salt of bupropion (HCl) can cause seizures, it is important to determine if the HBr salt may be less likely to cause seizures than the HCl salt. In the present animal studies this was evaluated by means of quantified electroencephalogram (EEG), observation, and the rotarod test in mice and rats. Both bupropion salts were tested at increasing equimolar doses administered intraperitoneally. The results in mice showed that bupropion HCl 125 mg/kg induced a significantly higher ten-fold increase in the mean number of cortical EEG seizures compared to bupropion HBr (7.50 +/- 2.56 vs 0.75 +/- 0.96; p = 0.045), but neither drug caused any brain injuries. In rats bupropion HBr 100 mg/kg induced single EEG seizure activity in the cortical and hippocampal (depth) electrodes and in significantly (p < 0.05) fewer rats (44%) compared to bupropion HCl, which induced 1 to 4 convulsions per rat in all rats (100%) dosed. The total duration of cortical seizures in bupropion HCl-treated rats was significantly longer than the corresponding values obtained in bupropion HBr-treated rats (424.6 seconds vs 124.5 seconds respectively, p < 0.05). Bupropion HCl consistently induced more severe convulsions at each dose level compared to bupropion HBr. Both treatments demonstrated a similar dose-dependent impairment of rotarod performance in mice. In conclusion, these findings suggest that bupropion HBr may have a significantly lower potential to induce seizures in mice and rats, particularly at higher doses, compared to bupropion HCl. Determination of this potential clinical advantage will require human studies. If confirmed by such studies, it is likely that this potential beneficial clinical benefit would be due to the presence of the bromide salt given the long history of the use of bromide to treat seizure disorders.

The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals.

In Brief

1. Tahniat Syed, MD, MPH 2. Mario Cruz, MD 1. Drexel University College of Medicine St. Christopher's Hospital for Children Philadelphia, Pa Barbiturates. Coupey SM. Pediatr Rev. 1997;18:260– 265[OpenUrl][1][FREE Full Text][2] Monitoring the Future: National Results on Adolescent Drug Use: Overview of Key Findings. Johnston LD, O’Malley PM, Bachman JG, et al. NIH Publication No. 05–5726. Bethesda, Md: National Institute on Drug Abuse; 2005 Barbiturates. In: Harvey RA, Champe PC, eds. Pharmacology. Philadelphia, Pa: JB Lippincott Company; 1992:96–98 Multiple-dose Activated Charcoal Compared to Urinary Alkalinization for the Enhancement of Phenobarbitol Elimination . Frenia ML, Schauben JL, Wears RL, et al. Clin Toxicol. 1996;34:169– 175[OpenUrl][3] Barbiturates are physically addicting sedative-hypnotic agents that can cause severe withdrawal symptoms. Their original role was to treat anxiety and insomnia, but they became popular drugs of abuse in the 1960s and 1970s and the most commonly used drugs in suicide attempts. Use of barbiturates has decreased significantly with stricter governmental regulations and with the advent of the much safer benzodiazepines. Current therapeutic uses of barbiturates are to treat seizure disorders, headaches, gastrointestinal disorders, and increased intracranial pressure and for anesthesia induction, but they have no analgesic properties. Adolescents abuse barbiturates to achieve a euphoric “high,” to offset the undesirable anxiety caused by stimulant drugs, and to attempt suicide. Monitoring the Future is a national survey of high school students that investigates their use of … [1]: {openurl}?query=rft.jtitle%253DPediatrics%2Bin%2BReview%26rft.stitle%253DPediatr.%2BRev.%26rft.issn%253D0191-9601%26rft.aulast%253DCoupey%26rft.auinit1%253DS.%2BM.%26rft.volume%253D18%26rft.issue%253D8%26rft.spage%253D260%26rft.epage%253D265%26rft.atitle%253DBarbiturates%26rft_id%253Dinfo%253Adoi%252F10.1542%252Fpir.18-8-260%26rft_id%253Dinfo%253Apmid%252F9255991%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=pedsinreview&resid=18/8/260&atom=%2Fpedsinreview%2F27%2F12%2Fe81.atom [3]: {openurl}?query=rft.jtitle%253DClin%2BToxicol.%26rft.volume%253D34%26rft.spage%253D169%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx

An Interaction Between Aspirin and Valproate: The Relevance of Plasma Protein Displacement Drug-Drug Interactions

An Interaction Between Aspirin and Valproate: The Relevance of Plasma Protein Displacement Drug-Drug Interactions

Splenic schooling dampens inflammation

When confronted with potentially lethal bacterial sepsis, the brain tells the spleen to shut down the production of inflammatory cytokines, according to Huston and colleagues on page 1623. This may help explain why splenectomy renders people more prone to the immunological overreaction of septic shock when infected with certain types of bacteria. Figure 1 Vagus nerve delivers antiinflammatory signals to the spleen. When the brain detects inflammation or injury, it sends signals along the vagus nerve—the meandering nerve that regulates vital functions such as heart rate and digestion. This signal triggers the release of the neurotransmitter acetylcholine (Ach) from peripheral nerve endings. Ach then binds to its receptor on immune cells and inhibits the production of inflammatory cytokines, in part by inhibiting the activation of the transcription factor NF-κB. This circuit is known as the cholinergic antiinflammatory pathway. Electrical stimulation of the vagus nerve suppresses cytokine production in several rodent models of inflammation. During bacterial sepsis, according to Huston et al., the vagus nerve's stop signal must be delivered to the spleen, as removing the spleen or severing the branch of the vagus nerve that innervates the spleen abolished the antiinflammatory effect. The spleen produced the bulk of the shock-inducing cytokine TNF in this model, possibly explaining why this organ had to receive the vagus nerve signal. But senior author Kevin Tracey suspects that Ach release always occurs in the spleen, even when the inflammation is happening elsewhere—a hunch they are now testing in an arthritis model. Tracey thinks that vagus nerve signals might educate white blood cells in the spleen, through which circulating cells transit every 2 to 3 min. How immune cells might translate this splenic schooling to inflammation control at distant sites remains to be determined. In the meantime, implanted pacemaker-like devices that zap the vagus nerve—used to treat seizure disorders—might also be useful for treating inflammatory diseases.

Intractable epilepsy: A survey of patients and caregivers

The social and health consequences associated with epilepsy are often magnified among patients with refractory epilepsy. Despite recent advances in the treatment of seizure disorders, many people with epilepsy continue to suffer from uncontrolled seizures and adverse side effects from medical therapy. This survey is the first to focus solely on the experiences, attitudes, and quality of life of a refractory epilepsy population, both those with the condition and their caregivers. To participate in this survey, respondents had to currently be experiencing seizures or troubling treatment side effects and had to have tried at least two different epilepsy medications. These survey data represent three groups of participants ( n = 903): those with epilepsy who self-reported on their condition (Group 1, n = 503), the caregivers of those with refractory epilepsy (Group 2, n = 200), and those with epilepsy who had their condition reported on by a caregiver (Group 3, n = 200). This survey revealed that the negative consequences associated with epilepsy tend to be greater among those experiencing treatment side effects and a greater number of seizures. Physicians must take into account medication side effects and quality-of-life issues when treating patients with epilepsy.