Complete Corpus Callosotomy Brings Worthwhile Seizure Reduction in Both Pediatric and Adult Patients.

BACKGROUND AND OBJECTIVES: The influence of the age at which complete corpus callosotomy (CC) surgery is performed on seizure outcomes remains unclear. This study aimed to evaluate the age-dependent aspects of long-term seizure outcomes after complete CC. METHODS: We reviewed 41 patients who underwent one-stage complete CC. Seizure outcomes were analyzed for age at epilepsy onset and at complete CC, focal MRI abnormality, and etiology. RESULTS: The median age was 7 months at epilepsy onset and 93 months at complete CC. The median follow-up duration was 67 months. Sixteen patients had focal MRI lesions and 4 had only general atrophy. Etiology was identified in 20 patients. For overall seizure outcomes (N = 41), complete seizure freedom was achieved in 5 patients, excellent seizure reduction (>80%) in 11, good (50%-80%) in 5, and poor (<50%) in 20. Freedom was correlated with younger age at complete CC and unknown etiology (P ≤ .05). Freedom was only achieved in patients aged younger than 7 years. Worthwhile (≥50%, freedom, excellent, and good) and not worthwhile (<50%, poor) overall seizure reduction showed no statistical difference in age at complete CC. No related factor was found for worthwhile overall seizure reduction. For drop attack outcomes (N = 31), freedom was achieved in 22 cases, excellent in 5, and poor in 4. Freedom was correlated with younger age at complete CC (P < .05) although freedom was achieved in 4 of 7 patients older than 20 years. Age at complete CC showed no statistical difference between worthwhile (≥50%) and not worthwhile (<50%) drop attack reduction. Worthwhile drop attack reduction was correlated with unknown etiology (P < .05). Complications were mild and transient. CONCLUSION: Complete CC is an excellent surgical option based on favorable seizure outcomes and acceptable complications in our present study.

Super-selective injection of propofol into the intracranial arteries enables Patient's self-evaluation of expected neurological deficit.

INTRODUCTION: It is hard to realize the extent of the expected postoperative neurological deficit for patients themselves. The provision of appropriate information can contribute not only to examining surgical indications but also to filling the gap between patient and expert expectations. We hypothesized that propofol infusion into the intracranial arteries (ssWada) could induce focal neurological symptoms with preserved wakefulness, enabling the patients to evaluate the postsurgical risk subjectively. METHODS: Presurgical evaluation using ssWada was performed in 28 patients with drug-resistant epilepsy. Based on anatomical knowledge, propofol was super-selectively infused into the intracranial arteries including the M1, M2, and M3 segments of the middle cerebral artery (MCA), A2 segment of the anterior cerebral artery, and P2 segment of the posterior cerebral artery to evaluate the neurological and cognitive symptoms. We retrospectively analyzed a total of 107 infusion trials, including their target vessels, and elicited symptoms of motor weakness, sensory disturbance, language, unilateral hemispatial neglect (UHN), and hemianopsia. We evaluated preserved wakefulness which enabled subjective evaluations of the symptoms and comparison of the subjective experience to the objective findings, besides adverse effects during the procedure. RESULTS: Preserved wakefulness was found in 97.2% of all trials. Changes in neurological symptoms were positively evaluated for motor weakness in 51.4%, sensory disturbance in 5.6%, language in 48.6%, UHN in 22.4%, and hemianopsia in 32.7%. Six trials elicited seizures. Multivariate analysis showed significant correlations between symptom and infusion site of language and left side, language and MCA branches, motor weakness and A2 or M2 superior division, and hemianopsia and P2. Transient adverse effect was observed in 8 cases with 12 infusion trials (11.2 %). CONCLUSION: The ssWada could elicit focal neurological symptoms with preserved wakefulness. The methodology enables specific evaluation of risk for cortical resection and subjective evaluation of the expected outcome by the patients.

Remission of startle epilepsy provoked by acoustic stimuli following complete callosotomy: A case study.

Herein, we present the case of a 21-year-old man with a history of generalized tonic seizures since the age of 4 years. These seizures occurred either spontaneously or could be provoked by auditory stimuli such as the sounds of a vacuum cleaner or an electric shaver. Despite trials with 10 different anti-seizure medications, his seizures remained refractory. Interictal electroencephalography (EEG) revealed generalized epileptiform activity, whereas ictal EEG showed a generalized attenuation pattern. Magnetic resonance imaging revealed extensive chronic infarctions, predominantly in the bilateral cerebral watershed areas. At the age of 17, the patient underwent a one-stage complete callosotomy, which only achieved remission of auditory-provoked seizures. Based on this experience and published reports, we propose that the posterior corpus callosum, particularly the isthmus and anterior splenium, may be involved in seizures caused by unexpected sound stimuli.

Somatosensory evoked spikes in normal adults detected by magnetoencephalography.

OBJECTIVE: Somatosensory evoked spikes (SESs) have been reported only in children aged under 14 years and are considered as an age-dependent phenomenon. However, we detected SESs in adult patients with epilepsy using magnetoencephalography (MEG). The present study investigated whether MEG can detect SESs in normal adults. METHODS: Spontaneous MEG was recorded during measurement of somatosensory evoked fields (SEFs) for bilateral electrical median nerve stimuli in 30 healthy adults. RESULTS: Bilateral SESs were observed in 10 adults but none in the other 20 subjects. SESs consisted of one or two peaks, and the first peak latency corresponded to that of the second peak (M2) of SEFs. The first SES peak was identical to the M2 in isofield map pattern, as well as location and orientation of the equivalent current dipole (ECD). M2 ECD strength in the 10 subjects with SESs was larger (p <0.0001) than in 20 without SESs. CONCLUSIONS: All-or-nothing detection of bilateral SESs by MEG in normal adults must depend on the signal-to-noise issue of symmetrical SEFs and background brain activity. SIGNIFICANCE: Our results further confirm the higher sensitivity of MEG compared to scalp EEG for the detection of focal cortical sources tangential to the scalp such as SESs.

"Caterpillar sign" in corpus callosum associated with curvilinear pericallosal lipoma in MRI: A case report.

Lipoma of the corpus callosum, also known as pericallosal lipoma, is a rare congenital brain abnormality associated with corpus callosum dysgenesis or agenesis. Two morphological types are described: tubulonodular and curvilinear, with the latter being mostly asymptomatic. We present the case of a 30-year-old woman with epilepsy, whose magnetic resonance imaging revealed a "caterpillar sign" in the corpus callosum associated with a curvilinear pericallosal lipoma. The "caterpillar sign" in the corpus callosum showed low signal intensity on magnetization prepared rapid acquisition with gradient echo, high signal on fluid-attenuated inversion recovery, and low on susceptibility-weighted imaging, possibly indicating abnormal blood vessels penetrating from the ventricle to the posterior callosal vein. We need to be conscious of this unusual finding, particularly when considering surgical intervention in the corpus callosum in cases of pericallosal lipoma, to avoid vascular complications.

Assessment of language lateralization in epilepsy patients using the super-selective Wada test.

BACKGROUND: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). METHODS: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. RESULTS: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. CONCLUSIONS: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects.

Ongoing EEG artifact correction using blind source separation.

OBJECTIVE: Analysis of the electroencephalogram (EEG) for epileptic spike and seizure detection or brain-computer interfaces can be severely hampered by the presence of artifacts. The aim of this study is to describe and evaluate a fast automatic algorithm for ongoing correction of artifacts in continuous EEG recordings, which can be applied offline and online. METHODS: The automatic algorithm for ongoing correction of artifacts is based on fast blind source separation. It uses a sliding window technique with overlapping epochs and features in the spatial, temporal and frequency domain to detect and correct ocular, cardiac, muscle and powerline artifacts. RESULTS: The approach was validated in an independent evaluation study on publicly available continuous EEG data with 2035 marked artifacts. Validation confirmed that 88% of the artifacts could be removed successfully (ocular: 81%, cardiac: 84%, muscle: 98%, powerline: 100%). It outperformed state-of-the-art algorithms both in terms of artifact reduction rates and computation time. CONCLUSIONS: Fast ongoing artifact correction successfully removed a good proportion of artifacts, while preserving most of the EEG signals. SIGNIFICANCE: The presented algorithm may be useful for ongoing correction of artifacts, e.g., in online systems for epileptic spike and seizure detection or brain-computer interfaces.

Language MEG predicts postoperative verbal memory change in left mesial temporal lobe epilepsy.

OBJECTIVE: To clarify whether preoperative language magnetoencephalography (MEG) predicts postoperative verbal memory (VM) changes in left mesial temporal lobe epilepsy (LMTLE). METHODS: We reviewed 18 right-handed patients with LMTLE who underwent anterior temporal lobectomy or selective amygdala hippocampectomy, 12 with (HS+) and 6 without hippocampal sclerosis (HS-). Patients underwent neuropsychological assessment before and after surgery. MEG was measured with an auditory verbal learning task in patients preoperatively and in 15 right-handed controls. Dynamic statistical parametric mapping (dSPM) was used for source imaging of task-related activity. Language laterality index (LI) was calculated by z-score of dSPM in language-related regions. LI in the region of HS+ and HS- was compared to controls. The correlation between LI and postoperative VM change was assessed in HS+ and HS-. RESULTS: Preoperative LI in supramarginal gyrus showed greater right-shifted lateralization in both HS+ and HS- than in controls. Right-shifted LI in supramarginal gyrus was correlated with postoperative VM increase in HS+ (p = 0.019), but not in HS-. CONCLUSIONS: Right-shifted language lateralization in dSPM of MEG signals may predict favorable VM outcome in HS+ of LMTLE. SIGNIFICANCE: Findings warrant further investigation of the relation between regional language laterality index and postoperative verbal memory changes.

Referral odyssey plot to visualize causes of surgical delay in mesial temporal lobe epilepsy with hippocampal sclerosis.

The "odyssey plot" was used to visualize referral delays in epilepsy surgery. Participants were 36 patients (19 males; 13-67 years, median 27 years) with mesial temporal lobe epilepsy with hippocampal sclerosis (HS) who underwent resection surgery. The "referral odyssey plot" included five clinical episodes: seizure onset (T1), first visits to a non-epileptologist (T2) and to an epileptologist (T3), first admission to our epilepsy monitoring unit (EMU) (T4), and resection surgery (T5). For each patient, we identified the first seizure type: the physician who first diagnosed focal aware seizure (FAS), focal impaired awareness seizure (FIAS), focal to bilateral tonic-clonic seizure (FBTCS), and radiologically suspected HS. Within the overall delay (T1-T5, median 18 years; interquartile range [IQR] 14), non-epileptologist's delay (T2-T3, 11.5 years; IQR 12.25) was far (p < 0.0001) longer than patient's (T1-T2, 0 year; IQR 2.25), epileptologist's (T3-T4, 1 year; IQR 4), or after-EMU delay (T4-T5, 1 year; IQR 1). FAS onset cases had significantly longer T1-T2 (N = 5, median 7 years; IQR 6) than FIAS (N = 22, 0 year; IQR 1, p < 0.005) or FBTCS onset cases (N = 9, 0 year; IQR 0, p < 0.001). FAS was correctly diagnosed first by non-epileptologists in 17.9%, by out-patient epileptologists in 35.7%, and at the EMU in 46.4%. FIAS was correctly diagnosed first by non-epileptologists in 94.4% and by out-patient epileptologists in 5.6%. Non-epileptologists diagnosed FBTCS in all cases. HS was diagnosed by non-epileptologists in 13.9%, by out-patient epileptologists in 47.2%, and at the EMU in 38.9%. Early referral to epileptologists is most critical for early surgery. Early utilization of the EMU is highly recommended because FAS is often overlooked by outpatient epileptologists. The odyssey plot will be useful to improve the healthcare system for other types of epilepsy.

[Medical Treatment of Epilepsy].

Medical treatment is the primary therapy option for patients with epilepsy. Recently, the International League Against Epilepsy (ILAE) proposed that the current medications used to treat epilepsy should be referred to as 'antiseizure medications' (ASMs) due to the symptomatic effect exerted against seizures. The present article reviews the recent clinical practice guidelines (Clinical Practice Guidelines for Epilepsy 2018, in Japan, and the NICE guideline, published in April 2022) and expert opinions (USA, South Korea, and Spain) based on which the selection of ASMs has been discussed. The classification of seizure types and epilepsies should be examined before selecting the ASMs for each patient with epilepsy. For focal epilepsy, lamotrigine, levetiracetam, and lacosamide would be the first-line ASM, whereas, for generalized epilepsy, valproic acid, lamotrigine, and levetiracetam would be the first-line ASM. However, valproic acid is not to be prescribed to women of childbearing potential.

Causal involvement of medial inferior frontal gyrus of non-dominant hemisphere in higher order auditory perception: A single case study.

The medial side of the operculum is invisible from the lateral surface of cerebral cortex, and its functions remain largely unexplored using direct evidence. Non-invasive and invasive studies have proved functions on peri-sylvian area including the inferior frontal gyrus (IFG) and superior temporal gyrus within the language-dominant hemisphere for semantic processing during verbal communication. However, within the non-dominant hemisphere, there was less evidence of its functions except for pitch or prosody processing. Here we add direct evidence for the functions of the non-dominant hemisphere, the causal involvement of the medial IFG for subjective auditory perception, which is affected by the context of the condition, regarded as a contribution in higher order auditory perception. The phenomenon was clearly distinguished from absolute and invariant pitch perception which is regarded as lower order auditory perception. Electrical stimulation of the medial surface of pars triangularis of IFG in non-dominant hemisphere via depth electrode in an epilepsy patient rapidly and reproducibly elicited perception of pitch changes of auditory input. Pitches were perceived as either higher or lower than those given without stimulation and there was no selectivity for sound type. The patient perceived sounds as higher when she had greater control over the situation when her eyes were open and there were self-cues, and as lower when her eyes were closed and there were investigator-cues. Time-frequency analysis of electrocorticography signals during auditory naming demonstrated medial IFG activation, characterized by low-gamma band augmentation during her own vocal response. The overall evidence provides a neural substrate for altered perception of other vocal tones according to the condition context.

Ictal chest discomfort in a patient with temporal lobe seizures and amygdala enlargement.

Chest discomfort is the representative symptom of dangerous coronary artery disease (CAD), but rarely occurs in patients with seizures. We treated a 74-year-old man with right mesial temporal lobe epilepsy and amygdala enlargement, who was initially suspected of CAD and underwent repeated cardiac angiography because of recurrent episodes of paroxysmal chest discomfort starting from 68 years old. He visited an epileptologist and underwent long-term video electroencephalography monitoring (LTVEM), which confirmed right temporal seizure onset during a habitual episodes of "chest discomfort," stereotyped movement of chest rubbing with the right hand, followed by impaired conscousness. Brain magnetic resonance imaging revealed right amygdala enlargement. The present case emphasizes the importance of the wide range of symptoms, such as chest discomfort, which may associated with epielpsy and result in a delayed diagnosis. LTVEM is useful for diagnosis of epilepsy with unusual seizure semiology by recording ictal EEG changes during chest discomfort.

Interhemispheric asymmetrical change in gray matter volume in patients with unilateral hippocampal sclerosis.

Objectives: To clarify the interhemispheric asymmetrical change in gray matter volume (GMV) in unilateral hippocampal sclerosis (HS), we compared changes in GMV relative to normal subjects between the HS and contralateral or non-HS sides. Material and Methods: Forty-five patients with unilateral HS and 30 healthy subjects were enrolled. We quantified changes in GMV in the patients with HS as compared to GMV in the normal subjects by introducing the Z-score (Z-GMV) in each region or region of interest in unilateral HS. Then, we assessed the asymmetrically decreased regions, that is, regions with significantly higher Z-GMV on the HS side than the contralateral or non-HS side. Z-GMV was calculated according to the two templates of 58 regions per hemisphere covering the whole brain by anatomical automatic labeling (AAL) and 78 regions per cerebral hemisphere using the Anatomy Toolbox. Results: Seven and four regions in AAL and 17 and 11 regions in Anatomy Toolbox were asymmetrically decreased in the Left Hand Side (LHS) and Right Hand Side (RHS), respectively. Hippocampus and Caudate in AAL, five subregions of the hippocampus (CA1-3, Dentate Gyrus and hippocampus-amygdala-transition-area and 4 extrahippocampal regions including two subregions in amygdala (CM: Centromedial, SF: Superficial), basal forebrain (BF) (Ch4), and thalamus (temporal) in anatomy toolbox were common among LHS and RHS concerning asymmetrically decreased regions. Conclusion: By introducing Z-GMV, we demonstrated the regions with asymmetrically decreased GMV in LHS and RHS, and found that the hippocampus and extrahippocampal regions, including the BF, were the common asymmetrically decreased regions among LHS and RHS.

Distribution of postictal slowing has an additional yield to interictal epileptiform discharge in predicting surgical outcomes in temporal lobe epilepsy.

OBJECTIVE: To investigate whether the slowing of bilateral postictal scalp electroencephalography (EEG) after focal impaired awareness seizures is associated with poor seizure outcomes after temporal lobe epilepsy (TLE) surgery. METHODS: This retrospective cohort study was conducted in the Department of Epileptology, Tohoku University Hospital from 2010 to 2020. The study included 42 patients with TLE who underwent a detailed presurgical evaluation and sequential resective surgery for the unilateral probable epileptogenic temporal lobe with 1 year or more of follow-up. We reviewed the interictal epileptiform distribution and those of the ictal and postictal epochs of the first focal impaired awareness seizure recorded in presurgical scalp EEG. We classified patients either with postoperative seizure-free status (Engel I) as group A or those with seizure persistence (Engel II-IV) as group B. RESULTS: Of 42 patients, 29 (69%) were classified into group A. Compared with group B, group A had a lower number of bilateral postictal polymorphic delta activity (PPDA) (10.3%: 61.5%) and bilateral interictal epileptiform discharges (IEDs) (13.8%: 69.2%) (P = 0.003, P = 0.001, respectively). A combined analysis of bilateral PPDA and IEDs per individual patient showed significantly more frequent seizure persistence after surgery (P < 0.0001) than a single analysis of bilateral IEDs or PPDA alone (P = 0.001). The regression analysis revealed that bilaterally distributed PPDA or IEDs had 13.50 or 13.72 times higher odds of persisting seizures within 1 year of surgery (95% confidence interval: 1.90-95.88; 2.12-88.87, respectively) (P = 0.009, 0.006). SIGNIFICANCE: The results of this study revealed that the bilateral distribution of PPDA was associated with poor postoperative seizure outcomes in patients with TLE, as well as bilateral IEDs. Additionally, the concomitant bilateral distribution of interictal and postictal changes is a strong indicator of poor surgical outcomes.

Determination of language areas in patients with epilepsy using the super-selective Wada test.

The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the "super-selective Wada test" (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

Development and validation of the Japanese version of the Epilepsy Stigma Scale in adults with epilepsy.

BACKGROUND: Self-stigma is considered to have immensely negative influences on the living and psychological states in patients with epilepsy. Understanding the stigma experienced by patients with epilepsy is essential considering its negative impact on their treatment and quality of life (QOL). However, few sufficiently validated self-report instruments are available to evaluate self-stigma in patients with epilepsy. The Epilepsy Stigma Scale (ESS) is one of the most commonly used self-reported questionnaires available to evaluate self-stigma in patients with epilepsy. The present study translated the ESS into Japanese to validate the Japanese version of the ESS (ESS-J) in Japanese adults with epilepsy. METHODS: The study included 338 patients with epilepsy (166 men, aged 18-75 years) who underwent comprehensive assessment including long-term video-electroencephalography monitoring, neuroimaging studies, and neuropsychological and psychosocial assessments in the Tohoku University Hospital Epilepsy Monitoring Unit. This study consisted of two phases: (1) translation of the ESS into Japanese using the back-translation technique; and (2) statistical analysis of the ESS-J to evaluate the factor structure, reliability, and validity. RESULTS: The 2-factor model achieved acceptable fit to the data: χ2 = 161.27, df = 34, p < 0.01, comparative fit index = 0.929, root mean square error of approximation = 0.105, standardized root mean squared residual = 0.047, Akaike's information criterion = 203.27 and, Bayesian information criterion = 283.56. These two subscales were named enacted stigma and felt stigma based on the theoretical model of self-stigma. We found the ESS-J to have acceptable internal consistency as follows: enacted (7 items; α = 0.88) and felt stigma subscale (3 items; α = 0.82). The concurrent validity was confirmed by adequate correlation with other related instruments. Both enacted and felt stigma had positive and moderate correlations with depression as measured by the Neurological Disorders Depression Inventory for Epilepsy (r = 0.44, p < 0.01; r = 0.41, p < 0.01, respectively) and with anxiety as measured by the Generalized Anxiety Disorder -7 (r = 0.48, p < 0.01; r = 0.38, p < 0.01, respectively). CONCLUSION: The ESS-J demonstrated acceptable validity and reliability. The present study provided preliminary evidence about the psychometric properties of the ESS-J, indicating the reliable factorial structure, adequate internal consistency, and satisfactory construct and concurrent validity. Measurement of the two types of self-stigma may offer a useful tool for clinical interpretation of patients' psychological state throughout epilepsy care, and as one of the patient-reported outcomes in QOL research.

Prescription trends in anti-seizure medications for adult patients with epilepsy in Japan: A retrospective cohort study using the database of health insurance claims between 2015 and 2019.

OBJECTIVE: To investigate whether newer anti-seizure medications (ASMs) are widely prescribed for a range of adult patients in Japan, including patients with previously and newly diagnosed epilepsy, or with focal and generalized epilepsies. METHODS: A retrospective cohort study was conducted using the Japanese insurance claims database including 8.4 million people to identify adults (≥16 years of age) with epilepsy diagnosis code identified between January 2015 and December 2018. Patients were included in the prevalent population if epilepsy was already diagnosed at baseline, and in the incident population if prior baseline data for at least 12 months included no epilepsy diagnosis code or ASM prescription. Patients were followed up from the month when the initial oral ASM was prescribed for up to 4 years until the end of 2019 as long as at least one ASM was prescribed. Proportions of prescribed oral ASMs were analyzed by population with epilepsy (prevalent vs. incident) and classification (focal vs. generalized). Anti-seizure medications were classified into older vs. newer ASMs according to the date of approval before and after 1990, respectively. RESULTS: A total of 24,691 patients fulfilled the eligibility criteria for the analysis. Of these, 21,046 and 3,645 were included in the prevalent and incident populations, respectively. The proportion of older ASMs significantly decreased, whereas the proportion of newer ASMs significantly increased (p < 0.0001) during the study period. This trend was more apparent in the population with incident epilepsy than in that with prevalent epilepsy, and was also apparent in the subgroup of focal epilepsy, but not in that of generalized epilepsy. Levetiracetam was the most frequently prescribed of the newer ASMs. CONCLUSION: Newer ASMs became more widely prescribed throughout the study period in populations with both prevalent and incident epilepsies, as well as the subpopulation with focal epilepsy. The advantages of newer ASMs such as better safety profiles may have led to the increasing proportions of prescriptions and newer ASMs may increase the treatment options for patients.