Lack of Association between the C3435T Polymorphism in the Human Multidrug Resistance (MDR1) Gene and Response to Antiepileptic Drug TreatmentCertain individuals with epilepsy appear resistant to multiple or all antiepileptic medications (AEDs). Among several reasons that can account for this resistance, one has been thought to be an excessive amount of a protein that transports drugs into and out of cells, called the P-glycoprotein (P-gp) drug transporter. The amount of P-gp is determined by a family of genes, one of which is called the multiple drug resistance gene,MDR1. We have investigated the prevalence of this genetic variant in a series of patients attending a specialist epilepsy clinic in an effort to explore the role ofMDR1in drug resistance. DNA samples were obtained from 400 patients, irrespective of seizure type or drug treatment. In total, 170 patients were classified as drug responders, with≥12 months' seizure freedom on current treatment. The remaining 230 patients were classified as nonresponders. Comparison of responders and nonresponders revealed no significant difference in the prevalence of the important variant of theMDR1gene. This study failed to corroborate a previously reported association between a known genetic variant in the humanMDR1gene and drug-resistant epilepsy. Other factors should continue to be investigated to explain AED resistance.Epilepsia2005;46(5). Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to CarbamazepineWhen AEDs are approved for use, the company must list all the side effects that occurred while patients took the drug. This study explores possible side effects when patients with epilepsy take topiramate (TPM) in addition to carbamazepine (CBZ) to control their symptoms. Most patients (71%) who took TPM had at least one side effect in the first few days of therapy. The most common side effects were sleepiness, headache, loss of appetite, nervousness, fatigue, dizziness, and upper respiratory tract infection. Of note, however, 63% of 92 patients who took a sugar pill (placebo) also complained of these same side effects. Almost all side effects appeared early during treatment and disappeared during treatment. The side effects that continued after the early period of treatment were weight loss and“paresthesia,” which is a tingly or numb feeling in the arms and legs. Therefore patients who are prescribed TPM to control their epilepsy may experience side effects during the first weeks of treatment. However for the vast majority, these effects will disappear with continued treatment, allowing a complete course of therapy.Epilepsia2005;46(5). Biting Behavior, Aggression, and SeizuresThe study reported an original description of behaviors rarely observed as ictal (during the seizure) or postictal (after the seizure) phenomena. Few articles have documented aggressive behaviors related to epileptic seizures by video-EEG recording. The authors discuss the significance of seizure-related aggressive displays, with particular reference to the act of biting another person. The main finding of the study is that seizure-associated violence depends on two main“conditions”: seizures with frontotemporal involvement (maybe encompassing the orbitomedial prefrontal cortex and amygdala) had to be present; and an appropriate external stimulus had to violate the patient's personal space. Triggering stimuli were both visual stimuli (the hand of the examiner) located around the patient's face and tactile ones applied near the mouth. The findings are discussed in light of the literature concerning epilepsy and aggression, human aggression. Behavioral data suggest that the biting behavior and related aggressive gestures can be considered as the emergence of instinctive behaviors meant to defend the personal space.Epilepsia2005;46(5). Self-reported Seizure Frequency and Time to First Event in the Seizure Monitoring UnitOver the past several years, it has become very clear that for patients with seizures that are not controlled by medications, admission to a hospital to record their seizures (video-EEG monitoring) is very helpful for determining the best treatment to stop the seizures. However, some patients have infrequent seizures, and many people, including the treating physician, the insurer, and the patient, may be concerned that no seizures will be recorded during a brief hospital stay. For this reason, these patients may not get monitoring. We tested the validity of this concern by looking at our patients who were monitored to see if any relation existed between the seizure frequency they reported in a clinic visit and the time it took to record a seizure during monitoring. We found no meaningful relation; most patients had a seizure within 7 days. We concluded that even patients with low seizure rates have seizures during monitoring, so low seizure rates should not prevent patients from getting monitoring.Epilepsia2005;46(5). Intracranial EEG Substrates of Scalp EEG Interictal SpikesEEG (electroencephalography, brainwave recordings) is an important test for the diagnosis of epilepsy. Although the EEG can be normal between seizures in people with epilepsy, about half will show brief, abnormal electrical discharges, called interictal (meaning“between seizures”) spikes. This study was performed to determine what part of the brain gives rise to these interictal spikes. We recorded simultaneously 26 channels of scalp EEG with additional electrodes in the brain in 16 surgery candidates with temporal lobe epilepsy. We reviewed∼600 interictal spikes recorded with intracranial EEG. Only a very few of these cortical spikes were associated with scalp recognizable potentials: 90% of cortical spikes with a source area of>10 cm2 produced scalp EEG spikes, whereas only 10% of cortical spikes having<10 cm2 of source area produced scalp potentials. Intracranial spikes with<6 cm2 of area were never associated with scalp EEG spikes. These data demonstrate that cerebral sources of scalp EEG spikes are larger than commonly thought. Synchronous or at least activation overlapping in time of 10–20 cm2 of brain cortex is common. Skull may actually serve a role in filtering out all but the most significant interictal discharges. This study helps us to understand better the likely spatial extent of the abnormal brain region that gives rise to EEG spikes correlated with certain types of epilepsy. Epilepsia 2005;46(5). Occipital Lobe Epilepsy: Clinical Characteristics, Surgical Outcome, and Role of Diagnostic ModalitiesOccipital lobe epilepsy is a relatively rare epilepsy syndrome in which seizures originate from the occipital lobe (posterior pole of brain). To assess the role of various diagnostic methods, to identify a specific factor indicating a good surgical outcome, and to characterize the clinical features of occipital lobe epilepsy, we studied 26 patients who were diagnosed as having this type of epilepsy and who underwent epilepsy surgery. Diagnoses were established by standard presurgical evaluation methods, which included MRI, fluorodeoxyglucose–positron emission tomography (FDG-PET), ictal single-photon emission computed tomography (SPECT), video-EEG monitoring, and intracranial EEG monitoring. After epilepsy surgery, patients were followed up for≥2 years. Sixteen of the 26 became seizure free after surgery, and another eight patients experienced a favorable outcome but were not seizure free. Sixteen of the 26 patients experienced a type of visual phenomenon (i.e., visual hallucination, visual illusion, blindness, or a field defect). Interictal EEG showed focal occipital abnormal spikes in 50%. MRI showed focal abnormality in 73%. FDG-PET demonstrated focal abnormal area in 44%. Ictal SPECT was performed in 19 patients, and showed focal increase of blood flow in 37%. EEG during seizures correctly localized abnormal waves in 69%. No significant relation was found between the diagnostic accuracy of any modality and surgical outcome. The localizations of epileptogenic zones by these different diagnostic methods were complementary. The concordance of three or more modalities was significantly observed in seizure-free patients after surgery. Some specific visual phenomena indicated an occipital onset of seizure. Various diagnostic methods can be useful to diagnose this epilepsy, and a greater concordance between presurgical evaluation methods indicates a better surgical outcome.Epilepsia2005;46(5). Quantitative1HMRS and MRI Volumetry Indicate Neuronal Damage in the Hippocampus of Children with Focal Epilepsy and Infrequent SeizuresSeizures can induce structural and functional changes in the brain, in particular in the hippocampus (a key structure in the temporal lobe, often involved with seizures) of adult patients with epilepsy, but whether the hippocampus is affected in children with temporal, nonintractable epilepsy is poorly known. Proton magnetic resonance spectroscopy is a relatively new neuroimaging technique, able to track the concentration of certain chemical components of the brain, particularly chemicals calledN-acetyl group, creatine, phosphocreatine, choline, and myoinositol. We also measured the volume of hippocampus in the MRI to reveal volume changes of 11 pediatric outpatients (10 to 17 years) with nonsymptomatic focal epilepsy taking AEDs but still having infrequent seizures. Eight healthy volunteers (9 to 16 years) served as controls. Our results showed that the mean concentration ofN-acetyl group was significantly decreased both on the side of the brain giving rise to seizures and also the other side in the patients, compared with the control persons, in particular if the children had a history of generalized tonic–clonic seizures. The mean concentrations of choline, creatine, and myoinositol did not differ significantly between the patients and controls. Moreover, the mean volume of the seizure-side hippocampi in patients was significantly reduced compared with that of the controls. The present results suggest that size of the hippocampus and chemical changes in the hippocampus can occur in children with childhood-onset focal epilepsy, even if they have infrequent seizures. Moreover, our results indicate that seizure-induced changes, although less severe, may occur earlier than suggested in children with nonintractable epilepsy.Epilepsia2005;46(5). Hippocampal Sclerosis in Severe Myoclonic Epilepsy in Infancy: A Retrospective MRI StudyThe hippocampus is a structure in the brain's temporal lobe, known to be very involved with generation of seizures in some patients. Many patients with temporal lobe epilepsy show a type of scarring or“hardening” of the hippocampus, called hippocampal sclerosis (HS). Whether the HS results from seizures, causes seizures, or both, remains controversial. During the last 10 years, the causal relation of prolonged febrile convulsions and HS has been of great interest. Febrile convulsions, or seizures with fever, are common in children age 6 months to 6 years. Usually they are benign and do not lead to epilepsy. However, prolonged febrile convulsions are typical of the condition called severe myoclonic epilepsy in infancy (SMEI). We reviewed the magnetic resonance images (MRIs) of patients with SMEI to assess if they had developed HS during the course of disease. SMEI is a rare, difficult-to-treat epilepsy syndrome beginning in a healthy infant with prolonged one-sided or generalized tonic–clonic febrile seizures. In the second year of life, or near this time, new types of seizures appear, including atypical absences, myoclonic jerks, and complex partial seizures. Developmental delay becomes evident in the second year. In this study, 28 MRIs of 14 patients treated in our hospitals between 1996 and 2004 were reviewed. Ten of 14 showed HS. Four children's initial MRIs, made only years after the beginning of the disease, showed HS, but six patient's initial MRIs did not show any abnormality, and they developed HS during the course of the disease. Our data support the hypothesis that prolonged febrile convulsions might be responsible for HS, but other factors (individual sensitivity, genetic factors) could play a role, too. In addition, the lessons from this type of myoclonic epilepsy might not apply to other types of epilepsy.Epilepsia2005;46(5). Effect of ACTH Therapy for Epileptic Spasms without HypsarrhythmiaAdrenocorticotropic hormone (ACTH) is a natural hormone in the steroid category, which is produced by brain. For decades, ACTH has been advocated for treatment of infantile spasms in children. Infantile spasms, abnormal EEGs (with a pattern called hypsarrhythmia), and developmental problems are features of the syndrome called West syndrome (WS). However, not all children with epileptic spasms (ESs) meet the full diagnostic criteria for WS. We analyzed the short- and long-term effects of ACTH therapy for patients with ESs who did not meet the criteria of WS. The subjects were 30 patients, including 13 boys and 17 girls, who had received ACTH therapy between 1970 and 2003. We excluded patients with WS, but included those with a history of WS who no longer showed hypsarrhythmia at the period of ACTH therapy. The age at onset of ESs and at ACTH therapy ranged from 2 to 82 months, with a median of 18 months, and from 11 to 86 months, with a median of 29 months, respectively. Excellent responses were obtained in 19 (63%) patients and poor responses in 11 (37%) patients, as a short-term effect. Among 17 of the 19 patients with excellent short-term outcomes and a follow-up of longer than 1 year after the ACTH therapy, 8 patients have continued to be seizure free (29%; excellent long-term effect), whereas the remaining nine patients had a recurrence of seizures (complex partial seizures in four, generalized tonic seizures in three, ESs in two) at 9 months to 198 months (median, 49 months) after ACTH therapy. In addition, nine of the 17 patients demonstrated a localized frontal EEG focus after the ACTH therapy, although most of these had previously shown diffuse epileptic EEG abnormality. ACTH therapy is worth trying for patients with resistant ESs, even without features of WS. However, the long-term effect is uncertain because recurrences of various types of seizures, including focal seizures, frequently were observed.Epilepsia2005;46(5). Adding Video Recording Increases the Diagnostic Yield of Routine Electroencephalograms in Children with Frequent Paroxysmal EventsProlonged video-EEG monitoring has long been used in the diagnosis evaluation of epilepsy patients. More recently, outpatient short-term video-EEG of 2–8 h has been implemented for patients with frequent attacks. We used a much shorter approach, involving the addition of video recording to routine EEG studies in children. An analysis of the efficacy of this diagnostic approach between 2000 and 2004 was undertaken. Video recording was added to routine studies of children referred with very frequent clinical episodes. Indications for EEG included: paroxysmal (sudden) eye movements, tremor, suspected seizures, myoclonic jerks, staring episodes, tics, absence epilepsy follow-up, cyanotic events, and suspected nonepileptic seizures. Video recording was added to 137 of 666 EEG studies. Mean patient age was 4.8 years. Twenty-five percent were inpatients. The nature of the event could be determined in 61 (45%) studies, compared with 68% to 95% success rates of published studies using the 2- to 8-h outpatient video-EEG recording. Average EEG duration was 26 min. Paroxysmal eye movements, staring episodes, tics, and myoclonus showed the highest diagnostic yield. The rate of success was higher (55%) among children with mental retardation. Adding video recording to routine EEG helped solve the clinical question in 45% of cases referred for frequent paroxysmal events. This technique was useful for hospitalized and ambulatory children. Infants and children with paroxysmal eye movements, staring episodes, staring episodes, tics, and myoclonus especially benefited from this diagnostic means. Because of its low cost and the small discomfort imposed on the patient and his or her family, this technique should be considered as a first diagnostic step in children with frequent paroxysmal events.Epilepsia2005;46(5). Depression and Anxiety Disorders in Pediatric EpilepsyThis study examined 100 children with complex partial seizures (CPS) and 71 children with childhood absence epilepsy (CAE). The children with epilepsy were more depressed and anxious, and had more suicidal behavior than 93 normal children, aged 5-16 years. The children and their parents were interviewed and filled out questionnaires about the child's feelings, emotions, and behavior. The children also had testing of their intelligence and language. The parents provided information on the children's seizure disorder. We found a much higher rate in the children with epilepsy compared to the normal children for depression and anxiety disorder (30%), as well as for suicidal thoughts (20%). None of the children had made a suicide attempt. Anxiety was more frequent than depression in the children with epilepsy. Only 33% of the children received some form of mental health service. Younger age, lower verbal skills, and school problems were related to the presence of a diagnosis of depression or anxiety disorder. Suicidal thoughts were found more in children who had epilepsy for longer periods of time. The children with CPS had more depression than anxiety; whereas, those with CAE had more anxiety. These findings, together with the high rate of unmet mental health needs for children with epilepsy, emphasize the importance of early identification and treatment of anxiety disorders and suicidal ideation in children with CPS and CAE.Epilepsia2005;46(5). Screening for Major Depression in Epilepsy Using Common Self-report Depression InventoriesMajor depression is a common problem for individuals with chronic epilepsy. It is frequently unrecognized and untreated. A variety of self-report questionnaires are available, but their ability to identify major depression in people with epilepsy remains uncertain. The purpose of this study was to determine the ability of two common self report measures of depressive symptoms to identify major depression in people with epilepsy. A total of 174 adults with epilepsy underwent standardized psychiatric interviews to determine the presence of current major depression. Individuals completed two self-report depression questionnaires (Beck Depression Inventory-II[BDI-II] and Center for Epidemiological Study of Depression[CES-D]). The ability of these self-report questionnaires to identify major depression compared to the gold standard structured interviews was examined using diagnostic efficiency statistics. Both the BDI-II and the CES-D exhibited significant ability to identify major depression in individuals with epilepsy. Common self-report depression measures can be used to screen for major depression in clinical settings. Use of these measures will assist in the clinical identification of individuals with major depression so that treatment can be started.Epilepsia2005;46(5). Predictors for Negative Attitudes toward Subjects with Epilepsy: A Representative Survey in the General Public in AustriaThe quality of life of people with epilepsy is determined not only by the disease itself but also by prejudices and negative attitudes toward the disorder in the general public. In this questionnaire study we asked 2128 Austrian adults about their opinions concerning people with epilepsy, for example, whether they should do the same jobs, whether children suffering from epilepsy should go to regular schools and other similar questions. This was not the first survey of its kind. However, what we tried was to determine was the attributes of respondents that predisposes to negative attitudes. We found that 10% of Austrian adults have negative attitudes towards people with epilepsy– a figure that is similar to studies done in other societies– and that being male, and of low socio-economic background predispose to unfavorable attitudes. In addition, little theoretical knowledge about epilepsy, misconceptions of epilepsy as a form of insanity, and no personal acquaintance with someone with epilepsy independently led to negative attitudes. Information campaigns should try to combine theoretical knowledge about epilepsy with opportunities for personal acquaintance with people suffering from epilepsy. Input from patient interest groups is essential to this regard.Epilepsia2005;46(5). Development of a Validated Clinical Case Definition of Generalized Tonic-Clonic Seizures for Use by Community-based Health Care ProvidersEpilepsy is a disease characterized by sudden movement of body and limbs due to discharge of electrical impulse in the brain. There are no proven confirmatory laboratory tests for its diagnosis and doctors often rely only on the detailed history to arrive at the diagnosis. It is estimated that almost 80% of epilepsy patients are not being treated. If the diagnosis of epilepsy is made simpler then it is possible that this treatment gap could be minimized. The type of epilepsy called generalized tonic-clonic seizures (GTCS) are amenable to easy diagnosis by their presentation. This paper tries to identify points in the detailed history used by neurologists which can be used by community-based health care providers after training to come to a conclusion as to whether a patient coming to them with a symptom of rigidity or jerkiness of limbs or body has GTCS. The study compares the reported symptomatology of patients with GTCS and non-GTCS patients with seizures in India. It identifies six questions based on the data analysis and clinical experience that can help in this decision making. These six questions are: absence of stress, presence of frothing, event occurring during sleep, incontinence during the episode, unconsciousness and injury during the episode. A case definition consisting of giving one point to an affirmative answer for each of the six questions was tested in five countries of the South East Asia Region. At a cutoff point of four out of six, this case definition rightly identified 72% of GTCS cases and all non-GTCS cases. The success of this simple question screen may make it easier to identify people with epilepsy in areas lacking sophisticated medical testing and systems.Epilepsia2005;46(5). Cost-effectiveness of First-line Antiepileptic Drug Treatments in the Developing World: A Population-level AnalysisDespite the negative impact of epilepsy on public health, there remains a yawning treatment gap in most developing regions of the world. In order to stimulate new investment into its appropriate management, there is a need to clearly demonstrate that interventions for epilepsy are not only effective and sustainable, but also affordable.WHO has embarked on a new initiative to assemble information on the cost-effectiveness of key health interventions in different subregions of the world. As part of this, costs and effects of older and newer anti-epileptic drugs (AEDs) provided in primary care were compared to a“do nothing” scenario (i.e. the untreated natural history of epilepsy). Effectiveness was expressed in terms of disability-adjusted life years or DALYs averted (a population-level summary measure of reduced burden) and costs were expressed in international dollars.Across nine developing WHO subregions, extending AED treatment coverage to 50% of primary epilepsy cases would avert between 150-650 DALYs per one million population (equivalent to 13-40% of the current burden), at an annual cost per capita of I$ 0.20-1.33. Older first-line AEDs (phenobarbital, phenytoin) were most cost-effective on account of their similar efficacy but lower acquisition cost (I$ 800-2,000 for each DALY averted).The main conclusion of the study is that a significant proportion of the current burden of epilepsy in developing countries is avertable by scaling-up the routine availability of low-cost antiepileptic drugs. Critical factors in the successful implementation of such a scaled-up level of service delivery, apart from renewed political support and investment, relate to appropriate training and continuity of drug supply.Epilepsia2005;46(5). A Comparison of Epilepsy Patients in a Traditional Ambulatory Clinic and a Telemedicine ClinicTelemedine is medical care at a distance, assisted by modern communication and computer technology. Patients are attended by a local nurse, technician or nonspecialist physician, and the video image and sound is sent in near-real-time to a specialty clinic. A joint project between the UTMB Telehealth Center, the Epilepsy Foundation of Southeast Texas, and the Texas Department of Health, compared the outcomes of care from a traditional epilepsy clinic in the ambulatory care center of a large academic medical center with the outcomes in a telemedicine epilepsy clinic.Demographic and outcome data were collected on patients in both clinics for three months in 2004. The authors gathered data on the number of seizures, hospitalizations, and emergency room visits. In addition, medication compliance was also measured by self-report and medication levels. There were no significant differences in any of the demographic data or outcome measures between the two groups.Telemedicine is an acceptable alternative to in-person clinics for the provision of care to adults with epilepsy. Since telemedicine programs bring medical care closer to where patients live, these clinics provide an excellent alternative to provide consistent, specialty care in rural and geographically isolated areas. Additional studies are needed to investigate the potential costs associated with telemedicine as well as the potential for cost savings over time as patients are more able to access specialty care.Epilepsia2005;46(5). Plasma Concentrations of Risperidone and Olanzapine during Co-administration with OxcarbazepineOxcarbazepine is a second-generation antiepileptic with mood-stabilizing properties. Unlike carbamazepine which is an inducer of the cytochrome P450 isoforms and may accelerate the elimination of several therapeutic agents, oxcarbazepine seems to have only a modest inducing action. In order to investigate the interaction between oxcarbazepine and the novel antipsychotics risperidone and olanzapine, we carried out drug monitoring of plasma concentrations of these antipsychotics in patients with bipolar or schizoaffective disorder given oxcarbazepine as a mood stabilizer. Oxcarbazepine, at a dose of 900-1200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years. Twelve patients were stabilized on risperidone therapy (2-6 mg/day) and 13 on olanzapine (5-20 mg/day). Plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by HPLC before addition of oxcarbazepine and after 5 weeks from the start of adjunctive treatment. Coadministration of oxcarbazepine caused only minimal and no significant changes in the mean steady-state plasma levels of risperidone, 9-OH-risperidone and olanzapine. In addition, its combination with either risperidone or olanzapine was well tolerated. These results indicate that oxcarbazepine does not affect the elimination of risperidone and olanzapine and confirm that this agent has a low potential for metabolically based drug interactions. Based on these findings, oxcarbazepine may be added safely to psychiatric or epileptic patients receiving maintenance treatment with risperidone or olanzapine.Epilepsia2005;46(5). Levetiracetam Concentrations in Serum and in Breast Milk at Birth and during LactationWe studied the concentration of the antiepileptic drug levetiracetam (LEV, Keppra®) in blood and in breast milk at birth and during lactation. Eight consecutive breast-feeding women with epilepsy treated with LEV twice daily and their infants were included in the study. The mean ratio between the concentration of LEV in the umbilical cord blood and the mothers' blood was 1.14, ranging from 0.97 to 1.45) (n= 4). The mean ratio between the concentration in the milk and the concentration in the mothers' blood was 1.00, ranging from 0.76 to 1.33 at three to five days after delivery (n= 7). At sampling two weeks to 10 months after delivery (n= 5) it was similar (range, 0.85–1.38). By three to five days after delivery, the infants had very low blood concentrations of LEV (less than 10–15μmol/L), a finding that persisted during continued breast-feeding. No malformations were detected, and none of the infants developed signs of adverse effects. In conclusion, levetiracetam readily crosses the placenta and is excreted into breast milk. Breast-fed infants usually have very low concentrations of the drug in the blood probably due to a rapid elimination. Women with epilepsy should in general be encouraged to nurse their infants. Treatment with levetiracetam forms no exception.Epilepsia2005;46(5). Is Variation in the GABA(B) Receptor 1 Gene Associated with Temporal Lobe Epilepsy?Some genes are believed to influence susceptibility to epilepsy. A gene known as GABA(B) receptor 1 has been linked to temporal lobe epilepsy in a recent genetic study. GABA is important because it is the main inhibitory neurotransmitter in brain. The GABA(B) receptor is one type of receptor site at which GABA binds to neurons to exert its effects. In this study, done in Italy, people who have a rare variant the gene for GABA(B) receptors appeared to have an increased risk of temporal lobe epilepsy. However, results of these types of genetic studies can be affected by the way in which the study was conducted. We therefore performed a similar genetic study in white Australians, adhering to existing guidelines for conducting such studies. We looked at over 200 Australians with temporal lobe epilepsy, but we did not find a similar link between the GABA(B) receptor 1 gene and temporal lobe epilepsy. We believe that our findings either reflect limitations in the way which the first study was conducted, or that different populations from different countries may have different genes influencing epilepsy risk. Further research into this gene and temporal lobe epilepsy is needed.Epilepsia2005;46(5). Deep EEG Recordings of the Mammillary Body in Epilepsy PatientsThe search continues for structures in the brain involved in the generation or spread of epileptic seizures. One structure that may be important, but has not received much attention from clinical epilepsy studies is the hypothalamus, and its posterior segment, called the mammillary bodies (MB). The electrophysiological patterns of MB have been well-documented in laboratory studies with animal models of epilepsy. Other studies have demonstrated the important role played by the MBs in seizure propagation. Our group embarked on a double-blind, cross-over pilot trial to evaluate the therapeutic effect of deep brain stimulation (DBS) of MB and its outflow fibers in patients with uncontrolled epilepsy. Here we aim to report, for the first time, the epileptic and nonepileptic discharges recorded within MB in patients with uncontrolled epilepsy. Three adult males were enrolled after obtaining the ethical committee approval and an informed consent from each. These patients were not believed to be curable by existing medicines or surgical procedures. DBS electrodes were implanted into the left and right MBs, with the patient under general anesthesia. Location was verified by magnetic resonance imaging (MRI). We obtained a surface-depth electroencephalogram (EEG) for a 2–4 day period under vigilant monitoring of the cardio-respiratory and memory functions. The background pattern of EEG recorded from MB was low-amplitude waves with mixed frequencies between 7–12 cycles/sec. We recorded several deep discharges of an epileptic type in each patient, which sometimes did and sometimes did not correlate with behavioral and EEG seizures. Seizure-associated discharges can be observed in human MB and differs from rhythmic EEG activity recorded in animals. These data supplement those available from animal observations.Epilepsia2005;46(5). [ABSTRACT FROM AUTHOR]