Cortical Excitability by Transcranial Magnetic Stimulation as Biomarkers for Seizure Controllability in Temporal Lobe Epilepsy.

OBJECTIVE: To investigate whether indicators of cortical excitability are good biomarkers of seizure controllability in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Three groups of subjects were recruited: those with poorly controlled (PC) TLE (N = 41), well-controlled (WC) TLE (N = 71), and healthy controls (N = 44). Short- and long-latency recovery curves were obtained by paired-pulse transcranial magnetic stimulation. Linear mixed effect models were used to study the effects of group, interstimulus interval (ISI), and antiepileptic drugs on long-interval intracortical inhibition (LICI) and short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). RESULTS: The mixed effect model that did not incorporate antiepileptic drugs showed that group and ISI were significant factors for LICI and SICI/ICF. LICI in the healthy control group was greater than in the two epilepsy groups, and the difference was significant at ISIs of 50, 150, and 200 msec. In contrast, SICI/ICF in the PC group was greater than in the healthy control and WC groups, and the difference was significant at an ISI of 15 msec. However, due to large variance, it was difficult to identify a cutoff value with both good sensitivity and good specificity. Incorporating the information of antiepileptic drugs to the mixed effect model did not change the overall results. CONCLUSIONS: Although LICI and SICI/ICF parameters were significantly different at the group level, they may not be suitable biomarkers for the controllability of TLE at the subject level.

Efficacy, safety, and tolerability of perampanel in Asian and non-Asian patients with epilepsy.

People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non-Asian populations with refractory focal seizures with or without focal to bilateral tonic-clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo-controlled, phase-3 studies involving patients aged ≥12 years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12 mg perampanel (or placebo) by the end of a 6-week titration period and for a further 13 weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28 days, and 50% and seizure-freedom responder rates relative to baseline. The median percent change in seizure frequency per 28 days from baseline was significantly greater than placebo for perampanel 8 and 12 mg (-31.1% and -38.1% change, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (-21.1% [P = 0.0001], -26.3% [P < 0.0001], and -27.7% [P = 0.0001] change, respectively) in the non-Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12 mg (40.1% and 43.8%, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (29.4% [P = 0.0002], 32.8% [P < 0.0001] and 34.5% [P = 0.0001]), respectively, in the non-Asian population. Seizure-freedom rate among all patients was 4.9%-11.7% for perampanel 2, 4, 8, and 12 mg. The most frequently reported treatment-emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk-benefit profile in both Asian and non-Asian populations with refractory focal seizures.

Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.

BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal-onset seizures (FOS). METHODS: Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs. RESULTS: In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p < 0.0001) with BRV 50 mg/day and 200 mg/day, respectively, 50% responder rate was 19.0%, 41.1%, and 49.3% with placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p < 0.0001 for both BRV groups vs. placebo). Median percent reduction in FOS frequency from baseline was 21.3%/38.9%/46.7% in patients on placebo/BRV 50 mg/BRV 200 mg/day, respectively. Overall, 0, 7 (4.6%), and 10 (6.8%) patients were classified as seizure-free during the treatment period on placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p = 0.0146/p = 0.0017 for BRV 50 mg/200 mg/day vs. placebo, respectively). TEAE incidences were similar between patients on placebo (58.4%) and all patients receiving BRV (58.5%); TEAE incidences for BRV 50 mg/day and BRV 200 mg/day were 57.0% and 60.1%, respectively. Overall, 0.7% of patients on placebo and 2.0% of all patients on BRV reported serious TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 1.3% and 2.7%, respectively), 20.1% of patients on placebo and 33.1% of all patients on BRV reported drug-related TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 26.5% and 39.9%, respectively), and 4.7% of patients on placebo and 3.0% of all patients on BRV discontinued due to TEAEs (discontinuation incidences for BRV 50 mg/day and BRV 200 mg/day were 2.6% and 3.4%, respectively). SIGNIFICANCE: Adjunctive BRV was efficacious and well tolerated in adult Asian patients with FOS. Efficacy and safety profiles were consistent with BRV studies in predominantly non-Asian populations. PLAIN LANGUAGE SUMMARY: Brivaracetam is used to treat partial or focal seizures in people with epilepsy. Most studies with brivaracetam tablets have involved people from non-Asian racial backgrounds. In this study, 449 Asian adults with epilepsy took part. One third took 50 mg of brivaracetam, one third took 200 mg of brivaracetam, and one third took a placebo each day for 12 weeks. On average, those who took brivaracetam had fewer seizures than those given the placebo. Most of the side effects were mild and the number and type of side effects seen were as expected for this medication.

Model-based spike detection of epileptic EEG data.

Accurate automatic spike detection is highly beneficial to clinical assessment of epileptic electroencephalogram (EEG) data. In this paper, a new two-stage approach is proposed for epileptic spike detection. First, the k-point nonlinear energy operator (k-NEO) is adopted to detect all possible spike candidates, then a newly proposed spike model with slow wave features is applied to these candidates for spike classification. Experimental results show that the proposed system, using the AdaBoost classifier, outperforms the conventional method in both two- and three-class EEG pattern classification problems. The proposed system not only achieves better accuracy for spike detection, but also provides new ability to differentiate between spikes and spikes with slow waves. Though spikes with slow waves occur frequently in epileptic EEGs, they are not used in conventional spike detection. Identifying spikes with slow waves allows the proposed system to have better capability for assisting clinical neurologists in routine EEG examinations and epileptic diagnosis.

Topiramate related reversible erectile dysfunction in temporal lobe epilepsy.

Topiramate (TPM) is a newer antiepileptic drug with high efficacy in treating various neurological disorders, especially epilepsy and migraine. The adverse effects of TPM therapy are mainly central nervous system-related somnolence and dizziness. There are rare reports about the role of TPM on sexual effects, but with inconsistent results. In this report, we describe a 31-year-old man who developed erectile dysfunction after several months of TPM use. Complete urological and sexual psychiatric evaluations were done. There was lack of an identifiable organic basis and psychiatric pathology in this patient. The erectile dysfunction improved only after the termination of TPM, documenting the temporal relationship. We reviewed and discussed the clinical aspect of TPM use in erectile dysfunction. This case and the rare cases of erectile dysfunction in TPM use reported in the literature show that TPM is worth to be paid attention to whenever it is prescribed in a wide range of neurological disorders.

Hyperventilation-induced ictal fear in nonlesional temporal lobe epilepsy.

Hyperventilation is a traditional seizure-provoking procedure used mainly in idiopathic generalized epilepsy and with a relatively limited role in partial epilepsy. Ictal fear is a rare seizure semiology seen in temporal lobe epilepsy. It has been suggested that the amygdala and anterior hippocampus are involved in generating ictal fear. We describe a rare patient with nonlesional temporal epilepsy who, while hyperventilating during an electroencephalography recording, developed complex partial seizures presenting as ictal fear. The particular sensitivity of the anterior hippocampus (probably the amygdala) to hypocapnia might be an important factor contributing to seizures. To avoid misdiagnosing this unusual condition as a pseudo-seizure, a detailed history and seizure semiology, as well as a concurrent electroencephalography recording, are mandatory.

Somatosensory rub evoked reflex epilepsy of a temporal lobe origin.

Somatosensory rub reflex epilepsy, evoked by prolonged or repetitive cutaneous contact of a circumscribed body area, is an unusual form of reflex epilepsy. The peculiar complaints and the negative interictal electroencephalographic (EEG) recordings make it difficult to identify the epileptic origin. Here we report an unusual case whose seizures would be evoked by a touch or rub on a unilateral arm and shoulder, with a contralateral temporal lobe origin, demonstrated in immediate postictal single-photon emission computed tomography (SPECT).

[Treatment guidelines for acute and preventive treatment of cluster headache].

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated both the acute and the preventive treatments for cluster headache now being used in Taiwan, based on the principles of evidence- based medicine. We assessed the quality of clinical trials and levels of evidence, and referred to other treatment guidelines proposed by other countries. Throughout several panel discussions, we merged opinions from the subcommittee members and proposed a consensus on the major roles, recommended levels, clinical efficacy, adverse events and cautions of clinical practice regarding acute and preventive treatments of cluster headache. The majority of Taiwanese patients have episodic cluster headaches, because chronic clusters are very rare. Cluster headache is characterized by severe and excruciating pain which develops within a short time and is associated with ipsilateral autonomic symptoms. Therefore, emergency treatment for a cluster headache attack is extremely important. Within the group of acute medications currently available in Taiwan, the subcommittee determined that high-flow oxygen inhalation has the best evidence of effectiveness, followed by intranasal triptans. Both are recommended as first-line medical treatments for acute attacks. Oral triptans were determined to be second-line medications. For transitional prophylaxis, oral corticosteroids are recommended as the first-line medication, and ergotamine as the second-line choice. As for maintenance prophylaxis, verapamil has the best evidence and is recommended as the first-line medication. Lithium, melatonin, valproic acid, topiramate and gabapentin are suggested as the second-line preventive medications. Surgical interventions, including occipital nerve stimulation, deep brain stimulation, radiofrequency block of the sphenopalatine ganglion, percutaneous radiofrequency rhizotomy and trigeminal nerve section, are invasive and their long-term efficacy and adverse events are still not clear in Taiwanese patients; therefore, they are not recommended currently by the subcommittee. The transitional and maintenance prophylactic medications can be used together to attain treatment efficacy. Once the maintenance prophylaxis achieves efficacy, the transitional prophylactic medications can be tapered gradually. We suggest the corticosteroids be used within two weeks, if possible. The duration of maintenance treatment depends on the individual patient's clinical condition, and the medications can be tapered off when the cluster period is over.

Nonketotic hyperglycemia-related reflex epileptic seizures induced by Mah-Jong playing.

Seizures related to nonketotic hyperglycemia (NKH) are often encountered in clinical practice. Among such seizures, reflex seizures are rare, and most of them are movement-induced focal seizures. We describe five patients with NKH and reflex seizures induced exclusively by playing Mah-Jong, a traditional and popular game in Chinese society. Four patients had partial seizures and one had a generalized seizure. All the patients manifested NKH on occurrence of the seizure. During Mah-Jong in the presence of NKH, seizures could arise from the frontal and temporal lobes, which are highly activated during the game. Both avoidance of Mah-Jong playing and control of glucose intake help prevent this disorder.

Fostering 2nd-year medical students' reflective capacity: A biopsychosocial model course.

OBJECTIVE: The biopsychosocial (BPS) model has been proposed to take into account the interaction of psychological and social factors in medical practice. Although some studies have explored its application in medical education, little has been evaluated about students' reflection in such courses. This study introduced a BPS model course and aimed to assess changes in students' reflective capacity resulting from this course. MATERIALS AND METHODS: Eighty-seven written reflections before and after the course were segmented, coded, and rated using the Reflection Evaluation for Learners' Enhanced Competencies Tool rubric, which contains six factors of reflective capacity, namely description of disease experience, presence, attending to emotions, description of conflict or disorienting dilemma, meaning making, and action. RESULTS: After the BPS model course, the overall reflective capacity, as well as the "Presence" and "Meaning making" scores, increased, while scores for "Attending to emotion" decreased significantly. "Description of disease experience," "Description of conflict or disorienting dilemma," and "Action" showed no significant change. CONCLUSION: Pedagogical suggestions are discussed for a BPS model course with reflective training for young medical students.

Diabetic hyperglycemia is associated with the severity of epileptic seizures in adults.

Epileptic seizures in diabetic hyperglycemia (DH) patients are not uncommon in clinical practice. Although there have been reports suggesting an association, most were limited case studies. The role of DH in the severity and recurrence of epileptic seizures remains unclear. We thus conducted a prospective comparative study of newly diagnosed unprovoked seizures in adult patients, with and without DH, from 2000 to 2004. Seizure semiology and severity were studied and all subjects were followed-up for 2 years to evaluate seizure recurrence. Forty-one patients in the DH and 70 patients in the non-DH group were recruited. Seizure clustering in initial presentation (63%) and in recurrence (78.6%) in the DH group was significantly higher than that in the non-DH group (38.5 and 41.4%) (p<0.05). In the DH group, the HbA1c at first seizure was significantly higher in patients with seizure recurrence than in those without (11.8% vs. 8.6%, p<0.05). Patients with poor glycemic control (HbA1c >9%) had significantly higher risk of seizure recurrence (44.8% vs. 8.3%) and clustering (79.3% vs. 25%) (p<0.05). In conclusion, DH might aggravate epileptic seizures. Severe seizures might be associated with recurrent seizures in patients with DH. DH should be investigated in adult patients with newly diagnosed epileptic seizures and aggressive blood sugar control might benefit seizure management in patients with DH.

Comparative cognitive effects of levetiracetam and topiramate in intractable epilepsy.

AIM: Anti-epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE. METHODS: This was a non-randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument. RESULTS: Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05). CONCLUSION: For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.

A randomized, double-blind, double-dummy, multicenter trial comparing the efficacy and safety of extended- and immediate-release levetiracetam in people with partial epilepsy.

PURPOSE: The aim of this trial was to compare the efficacy and safety of two formulations of levetiracetam in people with partial epilepsy over a 12-week treatment period. METHODS: We performed a randomized, paralleled, and multicenter trial that consisted of a 4-week single-blind placebo run-in, followed by a 12-week double-blind, double-dummy treatment phase to compare the efficacy and safety of levetiracetam extended-release (LEV-ER) and immediate-release (LEV-IR) tablets as an adjunctive treatment in adult patients with uncontrolled epilepsy. RESULTS: The median partial-onset seizure (POS) frequency per week (min-max) was 0.3 (0.0, 17.4; 95% confidence interval [95% CI] 1.3, 4.8) in the LEV-ER group and 0.3 (0.0, 31.4; 95% CI - 0.1, 4.3) in the LEV-IR group. No serious adverse events occurred during the trial period. Both groups had the same responder rate (58.6%), while a higher rate of seizure freedom over the treatment period was noted in the LEV-ER group compared with the LEV-IR group (27.6% vs. 13.8%, respectively). The European Quality of Life-5 Dimensions scores significantly increased in the LEV-ER-treated group, in contrast to the scores in the LEV-IR group, which decreased (7.2 vs. - 1.5, p = 0.03). CONCLUSION: These results suggest that LEV-ER is equivalent to LEV-IR in reducing the frequency of POS and has a similar tolerability as LEV-IR as an add-on therapy. In addition, LEV-ER treatment improved the health-related quality of life of people with uncontrolled partial epilepsy.

Sodium Metabisulfite: Effects on Ionic Currents and Excitotoxicity.

How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment. It was found that voltage-gated Na+ current (I Na) was stimulated, and current inactivation and deactivation were slowed in SMB-treated (30 µM) HL-1 cardiomyocytes. SMB-induced increases of I Na were attenuated in cells treated with ranolazine (10 µM) or eugenol (30 µM). The current-voltage relationship of I Na shifted to slightly more negative potentials in SMB-treated cells, the peak I Na with an EC50 value of 18 µM increased, and the steady-state inactivation curve of I Na shifted to a more positive potential. However, the tail component of the rapidly activating delayed-rectifier K+ current (I Kr) was dose-dependently inhibited. Cell-attached voltage-clamp recordings in SMB-treated cells showed that the frequency of action currents and prolonged action potential were higher. In SMB-treated NSC-34 neurons, the peak I Na was higher; however, neither the time to peak nor the inactivation time constant (I Na) changed. Pilocarpine-induced seizures were exacerbated, and acute neuronal damage and chronic mossy fiber sprouting increased in SMB-treated rats. Western blotting showed higher expression of the sodium channel in cells after chronic SMB treatment. We conclude that SMB contributes to the sodium channel-activating mechanism through which it alters cellular excitability and excitotoxicity in wide-spectrum excitable cells.

Vigabatrin-attributable visual field defects in patients with intractable partial epilepsy.

INTRODUCTION: Vigabatrin (VGB) is implicated to cause visual field defects. We estimated the prevalence, described the characteristics and investigated the risk factors of VGB-attributable visual field defects. METHODS: Patients with intractable partial epilepsy under VGB add-on treatment received static perimetric examinations. Visual field charts were reviewed and interpreted using a three-grade system. Clinical features and therapeutic courses were analyzed for possible risk factors. RESULTS: Visual field defects in at least one eye were detected in 27 (79%) of 34 patients. In the subgroup of 27 patients with both eyes reliably tested, 16 (59%) had bilateral defect, among whom seven were severely involved and showed nasally dominant, crescent or concentric defect. Five patients had unilateral visual field defects. Four out of the 27 affected patients reported blurred vision. No statistically significant differences were noted between patients with and without visual field defects in terms of gender, age, duration or etiology of the epilepsy, and duration, maximum daily dose, or cumulative dose of VGB. CONCLUSIONS: There was a high prevalence of VGB-attributable visual field defects. No risk factors could be identified. Routine initial and regular follow-up of visual field examination, especially that focusing within a range of central fixation to 60 degrees, should be performed in patients on VGB.

Current state of evidence-based practice education for undergraduate nursing students in Taiwan: A questionnaire study.

BACKGROUND: Evidence-based practice (EBP) has been emphasized as the core competency of undergraduate nursing students and must be cultivated before graduation. However, there is limited information of EBP education for undergraduate nursing students in Taiwan. OBJECTIVES: The purpose of this study was to investigate the current state of EBP education for undergraduate nursing students in Taiwan. DESIGN: A self-developed questionnaire, validated by experienced educators, was designed to explore curriculum design, teaching resources, qualification of teachers, and barriers regarding EBP education. PARTICIPANTS: A total of 21 nursing schools and colleges participated. The chair of each recommended a faculty member involved in teaching EBP as the school's representative to fill out the questionnaire. RESULTS: Among the 21 nursing schools and colleges, 18 (85.7%) had implemented EBP education in the curriculum. Among these schools, 22.2% conducted an independent EBP course, 50% incorporated EBP concepts into other courses, and the remainder offered both kinds of EBP courses. Multiple strategies were incorporated to teach the EBP. Less than 35% of the schools had designed or adopted standardized teaching materials and evaluated students' learning outcomes. Although 55.6% of the schools reimbursed faculty for participation in EBP training, 39% of their faculty members who taught EBP did not receive any EBP training. Shortage of qualified faculty and limited opportunity to involve students in evidence-based applications were reported as major obstacles to teaching EBP. CONCLUSIONS: EBP education has already gained the attention of nursing schools in Taiwan. However, lack of comprehensive EBP training among teachers and the difficulty of teaching clinical application of EBP require special consideration. In order to promote EBP education in undergraduate nursing curriculums, we suggest that nursing schools reinforce and support faculty to participate in formal EBP training. Also needed is a systematic curriculum design with multiple teaching strategies and links with clinical practicum.

Antioxidant and anticonvulsant effect of a modified formula of chaihu-longu-muli-tang.

Antiepileptic drug therapy in individuals with epilepsy can induce free radical generation and profound lipid peroxidation. Some Chinese herbs with antiepileptic potential show antioxidant effects. We performed an open add-on study of TW970, a modified formula of the Chinese medicine "chaihu-longu-muli-tang", on 20 patients with refractory epilepsy and a seizure frequency of at least four fits per month, and another 20 patients with benign epilepsy and a seizure frequency of less than four fits per month. The control group consisted of 20 age-matched healthy adults. Seizure frequency, serum malondialdehyde (MDA), glutathione (GSH) and copper-zinc superoxide dismutase (Cu,Zn-SOD) were investigated in patients with refractory and benign epilepsy before and after four months add-on treatment of TW970. There was a decrease in seizure frequency in refractory epileptics from 13.4 +/- 3.4 to 10.7 +/- 2.5/per month, although the p value was 0.084. Before TW970 add-on treatment, a significant enhancement of lipid peroxidation with increased MDA and Cu,Zn-SOD activities together with decreased GSH were seen in refractory epileptics compared with normal controls. After TW970 add-on treatment of refractory epileptics for four months, normalization of MDA and Cu,Zn-SOD levels was achieved. Before and after TW970 add-on treatment, there were no statistically significant changes of the above-mentioned parameters in the patients with benign epilepsy. These results suggest that TW970 can reduce the seizure frequency in patients with refractory epilepsy and this may be due to the antioxidant effects of the modified formula of chaihu-longu-muli-tang.