Cognitive dysfunction in drug-naïve late-onset temporal lobe epilepsy.

OBJECTIVES: To evaluate cognitive functions including memory in middle-aged and elderly patients with antiseizure drug-naïve late-onset temporal lobe epilepsy (TLE). METHODS: We performed assessments with the Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-Revised (WMS-R) in 26 antiseizure drug-naïve patients with late-onset TLE, in comparison to 30 healthy subjects. We investigated the relationships between these cognitive function scores and clinical characteristics, seizure frequency, and frequency of interictal epileptic discharges (IEDs). RESULTS: Patients with epilepsy had a significantly lower score than healthy controls in the verbal intelligence quotient (IQ), the performance IQ, and full-scale IQ in intelligence testing. Patients showed significantly decrease in the verbal memory scores, visual memory scores, general memory scores, and delayed recall scores compared with those in the control subjects. Delayed recall scores were significantly negatively correlated with recent seizure frequency and the total IEDs count per minute, but not with age of onset or duration of illness. SIGNIFICANCE: Patients with antiseizure drug-naïve late-onset TLE displayed cognitive deficits including the domains of memory by using standard clinical neuropsychological test. Patients with late-onset epilepsy need to be considered for cognitive dysfunction at the time of diagnosis of TLE because they may have their daily life and work affected not only by epileptic seizures but also by cognitive deficits. Appearance of seizures and EEG abnormalities may affect the memory function in patients with late-onset TLE.

Psychoses after an antiepileptic drug administration: Frequency, timing, and duration.

OBJECTIVES: To clarify the pathophysiology of psychoses after the new administration of antiepileptic drugs (AED), we analyzed the annual incidence, timing of development, and duration of episodes. METHODS: Psychotic outcomes in the first 6-month period after an AED or non-AED administration in patients with focal epilepsy were exhaustively reviewed in eight Japanese neuropsychiatry institutions. In cases with psychotic episodes, the subtype of psychosis, timing of development, previous history of psychosis, and duration of the episode were evaluated. RESULTS: Between 1981 and 2015, 5018 new drugs (4402 AED and 616 non-AED) were administered to 2067 patients with focal epilepsy. In the first 6-month period, 105 psychotic episodes occurred (81 interictal psychosis [IIP] and 24 postictal psychosis). Furthermore, 55 cases were first episodes and 50 were recurrent episodes. The frequency of psychoses is significantly higher after AED administration (n = 102) compared with non-AED administration (n = 3). Psychosis occurred most frequently in the initial 1-month period after new-AED administration and tended to decrease with increasing time. The estimated annual incidence of all psychoses after a new AED administration was 3.5% (2.0% for first-episode psychosis and 1.8% for first-episode IIP). Duration of psychoses (mean, 38.5 weeks) was equivalent to overall IIP. Duration of IIP did not shorten with discontinuation of newly administered AED. SIGNIFICANCE: Patients with epilepsy exhibit psychosis more frequently after new AED administration than after non-AED administration. This study shows the pathophysiology of psychoses after AED administration with annual incidence, the timing of development, and the duration of PAP, which have rarely been reported.

DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees. A total of 143 participants, including 43 familial patients, 5 suspected patients, 3 sporadic nonfamilial patients, 22 unaffected familial members, and 70 unrelated controls, were screened for expanded abnormal pentanucleotide repeats in SAMD12, TNRC6A, RAPGEF2, YEAT2, MARCH6, and STARD7. DNA samples were analyzed using Southern blotting, long-range polymerase chain reaction (PCR), repeat-primed PCR, and long-range PCR followed by Southern blotting. Of the 51 individuals with clinically diagnosed or suspected BAFME, 49 carried a SAMD12 allele with an expanded TTTCA/TTTTA pentanucleotide repeat. Genetic and clinical anticipation was observed. As in previous reports, the one patient with homozygous mutant alleles showed more severe symptoms than the heterozygous carriers. In addition, screening for expanded pentanucleotide repeats in TNRC6A revealed that the frequency of expanded TTTTA repeat alleles in the BAFME group was significantly higher than in the control group. All patients who were clinically diagnosed with BAFME, including those in the original family reported by Yasuda, carried abnormally expanded TTTCA/TTTTA repeat alleles of SAMD12. Patients with BAFME also frequently carried a TTTTA repeat expansion in TNRC6A, suggesting that there may be unknown factors in the ancestry of patients with BAFME that make pentanucleotide repeats unstable.

Quantitative psychopathology of interictal psychosis in epilepsy; interaction between epilepsy-related and psychosis-general effects.

OBJECTIVE: There is a historical debate whether psychopathology of epilepsy psychosis is unique to epilepsy or common to other psychoses. However, a large comprehensive studies on this issue are scarce. To clarify the characteristics of interictal psychosis (IIP), we evaluated psychopathology quantitatively. METHODS: This study included 150 patients with IIP (epilepsy+/psychosis+), 187 patients with schizophrenia (SC: epilepsy-/psychosis+), 182 patients with epilepsy (EP: epilepsy+/psychosis-), and 172 non-clinical individuals (NC: epilepsy-/psychosis-). The IIP group comprised 127 chronic and 23 brief psychoses. Age, sex, and years of education, onset and duration of psychosis, and onset and duration of epilepsy were matched among the groups. The psychopathology was evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS), which comprises three symptom factors namely negative symptoms (NS), positive symptoms (PS), and anxiety-depressive symptoms (ADS). RESULTS: For overall 16-BPRS and NS factor scores, there were significant interactions between epilepsy-related (epilepsy+/-) and psychosis-general (psychosis+/-) effects. The EP exhibited higher scores than did the NC, whereas the IIP exhibited lower scores than did the SC. For PS and ADS factor scores, the IIP and SC exhibited a significant psychosis-general effect. Chronic IIP was associated with more serious psychopathologies than was brief IIP. However, limited with chronic IIP, there was a significant interaction between epilepsy-related and psychosis-general effects on the overall 16-BPRS and NS factor scores. CONCLUSION: These findings demonstrate the first large quantitative evidence on the unique psychopathology of IIP which has been only narratively described. The psychopathology is associated with the interaction between epilepsy-related and psychosis-general effects.

Increased frequency of psychosis after second-generation antiepileptic drug administration in adults with focal epilepsy.

OBJECTIVE: Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP. METHODS: The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures. RESULTS: Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP. CONCLUSION: Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP.

Seizure activity and individual vulnerability on first-episode interictal psychosis in epilepsy.

OBJECTIVE: Despite a theoretical consensus that interictal psychosis (IIP) is related to various epilepsy-related factors, the impact of seizure activity on development of IIP remains inconclusive. This is the first controlled study using quantitative seizure-activity measures at the onset of IIP. METHODS: One hundred and eighty-one patients with epilepsy who exhibited first-episode IIP (IIP group) and 427 patients with epilepsy without psychotic episodes (control group) were enrolled. The control group was matched for age, epilepsy type, and duration of epilepsy. The two seizure-activity indices (seizure frequency at the time of onset of first-episode IIP and the number of seizures before the onset of IIP) were evaluated and compared between the IIP and control groups. Logistic regression analysis was used for extracting risk variables to develop first-episode IIP. RESULTS: The sum of previous seizures was greater in the IIP than in control groups. This was particularly the case in the patients with partial epilepsies (PE). Higher seizure frequency in the patients with PE was associated with the development of first-episode IIP while no association was found in the whole cohort or in the patients with generalized epilepsies (GE). Subsequent multivariate analysis revealed the sum of previous seizures and family history of psychosis as risk variables to first-episode IIP. CONCLUSIONS: The accumulation of seizure-related damages and family history of psychosis is associated with the onset of IIP episodes, particularly in the patients with PE. Seizure activity and individual vulnerability to psychosis are likely to be interacted for as the development of IIP in patients with epilepsy.

Dissociative experiences in epilepsy: effects of epilepsy-related factors on pathological dissociation.

Psychogenic nonepileptic seizures (PNESs) in patients with epilepsy can be categorized as dissociative disorders. The prevalence of PNESs in patients with epilepsy appears to be much higher than that of dissociative experiences in nonclinical subjects. In order to clarify as to whether epilepsy-related factors were associated with pathological dissociation, we conducted a controlled study with 225 patients with epilepsy and 334 nonclinically matched individuals. All participants completed the Japanese version of the Dissociative Experiences Scale (DES). There was no significant difference in the DES score (DES-S) between the group with epilepsy and the control group. The group with epilepsy showed a significantly higher DES taxon (DES-T; a subset of DES-S and an index of pathological dissociation) than the control group. Thirty-one out of the 225 patients with epilepsy (13.8%) had PNESs. Because of its strong association with the DES-S and DES-T, PNESs can be regarded as a symptom of dissociation. With multiple regression analysis, the patients with a shorter duration of epilepsy, higher seizure frequency, or shorter period in education tend to suffer from pathological dissociation. These findings demonstrate that patients with epilepsy are more prone to experiencing pathological dissociation when having certain clinical factors.

Anger is a distinctive feature of epilepsy patients with depression.

Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.

Effects of antipsychotic drugs on the duration of interictal psychotic episodes in patients with epilepsy.

Treatment protocols for interictal psychosis (IIP) of patients with epilepsy have not yet been established. We aimed to clarify the effects of antipsychotic drugs (APDs) on duration of IIP episodes. We studied 393 IIP episodes in 200 patients with epilepsy in accordance with our empirical treatment protocol. The duration of all the episodes and APD treatments were reviewed. Antipsychotic drugs were used in 338 episodes and not used in 55 episodes (non-APD group). The APDs used in the treatment of IIP episodes were divided into the following three groups: first-generation APDs (FAPD, n=252), second-generation APDs (SAPD, n=44), and the combination of first- and second-generation APDs (CAPD, n=42). The non-APD group showed a significantly shorter episode duration than did the APD group (F=6.05, p=0.014). Among the 3 APD groups (FAPD, SAPD, and CAPD), there was a significant difference in duration of IIP episode (F=8.65, p=0.000). Whereas the duration of episodes was significantly longer in the CAPD group than in the other two groups, it was not significantly different between the FAPD and SAPD groups. Our findings further to clarify the nature of IIP and add further perspectives on treatment protocols for IIP.

Interictal psychotic episodes in epilepsy: duration and associated clinical factors.

PURPOSE: There have been few reports showing the distribution of the duration of interictal psychosis (IIP) episodes and their association with clinical characteristics. To clarify the nature of IIP, we studied the duration of IIP episodes and their related factors. METHODS: One hundred fifty-five patients with epilepsy exhibited 320 IIP episodes during our follow-up period (mean 16.9 years). The duration of all the episodes and the longest episode in each patient during the follow-up periods were studied. Characteristics of the patients (e.g., epilepsy type, age of onset, and family history of psychosis) and episode-specific factors (e.g., age of the episode, seizure frequency, administrations of antiepileptic drugs [AEDs] and antipsychotic drugs [APDs]) were analyzed in association with the duration of the episodes. KEY FINDINGS: Mean duration of the 320 IIP episodes was 82.7 weeks and that of the longest IIP episodes was 150.1 weeks. During the follow-up period, 17 patients (11.0%) showed all episodes remitting within a month and 54 (34.8%) showed all episodes lasting for 6 months or longer. The IIP episodes that occurred at a younger age were often prolonged. Patients with a family history of psychosis or with early onset of psychosis tended to have more prolonged IIP episodes. Among the episodes treated with APDs, early administration of APDs was significantly associated with shorter IIP duration. SIGNIFICANCE: The distribution of the duration of IIP episodes indicated the broad spectrum and heterogeneity of the IIP phenomena. The individual vulnerability to psychosis may be associated with prolonged episodes. Administration of APDs soon after onset of the episodes appeared to be effective in controlling them. These findings support empirical treatment principles for IIP to administer APDs at an early stage of its development.

Analogy between psychosis antedating epilepsy and epilepsy antedating psychosis.

PURPOSE: Patients with recurrent epileptic seizures after the development of psychosis (Psychosis-Epilepsy) have been regarded as belonging to a different clinical entity from those with epilepsy antedating the development of psychosis (Epilepsy-Psychosis). However, clinical characteristics of patients with Psychosis-Epilepsy have not been well described, except for early German studies. We aimed to estimate the reliability of distinction between Psychosis-Epilepsy and Epilepsy-Psychosis by comparing their clinical characteristics. METHODS: Among 312 patients with epilepsy and psychosis enrolled in this multicenter study, 23 patients had Psychosis-Epilepsy and 289 patients had Epilepsy-Psychosis (i.e., interictal psychosis). Demographic (i.e., sex, age at time of evaluation, and intellectual functioning), psychiatric (i.e., age at onset of psychosis, subtype of psychosis, duration of psychotic episode, and a family history of psychosis), and epileptic (i.e., age at onset of epilepsy, subtype of epilepsy, seizure type, and a family history of epilepsy) characteristics of both groups were compared. KEY FINDINGS: Clinical characteristics, either in their psychoses or epilepsies, except for age-related variables, were equivalent between patients with Psychosis-Epilepsy and those with Epilepsy-Psychosis. Time intervals between onset of psychosis and that of epilepsy in the two groups showed a normal distribution curve. SIGNIFICANCE: The presence of many common features and the linear distribution of the time intervals did not fully support that Psychosis-Epilepsy and Epilepsy-Psychosis were two distinctly different entities. Among certain patients who have genetic vulnerabilities to both psychoses and seizures, psychosis may develop either antedating or postdating the development of epilepsy. These findings may suggest a necessary reconceptualization of psychoses in epilepsy.

One-year seizure prognosis in epilepsy patients treated with antidepressants.

To investigate the clinical effects of antidepressants on seizure frequency of patients with epilepsy treated with antiepileptic drugs, we retrospectively evaluated the 1-year course of seizure frequency. One hundred twenty-one patients with epilepsy treated with antidepressants and 300 patients with epilepsy not treated with antidepressants (controls) were the subjects of this study. Seizure frequency over the 1-year period of administration of antidepressants was retrospectively evaluated and compared with that for controls. In the patients with epilepsy taking antidepressants, seizure frequencies at four observation points (1, 3, 6, and 12 months after starting antidepressants) were equivalent to those of the control group. There was no significant difference in seizure frequency between first- and second-generation antidepressants. Patients with epilepsy treated with antiepileptic drugs can take antidepressants without a significant risk of exacerbation of seizures. Most antidepressants can be used for psychiatric treatment of patients with epilepsy.

Epileptic, organic and genetic vulnerabilities for timing of the development of interictal psychosis.

BACKGROUND: Age at the first psychotic episode and an interval between the onset of epilepsy and that of psychosis reflect developmental processes of interictal psychosis. However, factors relating to these indices remain unknown. AIMS: To identify clinical variables that are associated with the timing of the development of interictal psychosis. METHOD: In 285 adults with epilepsy with interictal psychosis, effects of epileptic (epilepsy type), organic (intellectual functioning) and genetic (family history of psychosis) variables on timing of the development of psychosis were examined. RESULTS: The mean interval between the onset of epilepsy and that of psychosis was 14.4 years. Some psychosis occurred within a few years of the first seizure. Generalised epilepsy, normal intellectual function and a positive family history of psychosis were associated with early onset of psychosis. CONCLUSIONS: Early development of interictal psychosis in people with epilepsy may reflect other individual vulnerabilities to psychosis rather than epilepsy-related damage.

Individual vulnerabilities to psychosis after antiepileptic drug administration.

BACKGROUND: Psychosis often develops after the administration of antiepileptic drugs (AEDs) in patients with epilepsy. However, the individual vulnerability and clinical condition of such patients have been rarely scrutinised. We investigated the effect of individually consistent (trait-dependent) and inconsistent (state-dependent) characteristics. METHODS: The individual characteristics, clinical states and psychotic outcome of patients from eight adult epilepsy clinics were retrospectively reviewed over 6-month periods after a new drug (AED or non-AED) administration between 1981 and 2015. RESULTS: A total of 5018 new drugs (4402 AEDs and 616 non-AEDs) were used in 2015 patients with focal epilepsy. Subsequently, 105 psychotic episodes (81 interictal and 24 postictal) occurred in 89 patients. Twelve patients exhibited multiple episodes after different AED administrations. Trait-dependent characteristics (early onset of epilepsy, known presumed causes of epilepsy, lower intellectual function and a family history of psychosis) were significantly associated with the patients who exhibited psychosis. Absence of family history of epilepsy was also associated with psychosis but not significantly. Subsequent logistic regression analysis with a model incorporating family history of psychosis and epilepsy, and intellectual function was the most appropriate (p=0.000). State-dependent characteristics, including previous psychotic history and epilepsy-related variables (longer duration of epilepsy, AED administration, higher seizure frequency and concomitant use of AEDs) were significantly associated with psychotic episodes. Subsequent analysis found that a model including AED administration and previous psychotic history was the most appropriate (p=0.000). CONCLUSION: Psychosis occurring after new AED administration was related to the individual vulnerability to psychosis and intractability of epilepsy.

Evaluation of dissociative experiences and the clinical utility of the Dissociative Experience Scale in patients with coexisting epilepsy and psychogenic nonepileptic seizures.

We investigated the relationship between dissociation and psychogenic nonepileptic seizures (PNES) and evaluated the clinical utility of the Dissociative Experience Scale (DES) in patients with epilepsy. The DES was administered to 30 patients with epilepsy and PNES, 50 patients with epilepsy and no PNES, and 85 nonclinical individuals. Patients with epilepsy and PNES scored significantly higher on the DES (29.3) than patients with epilepsy without PNES (13.5) and nonclinical individuals (11.1). High DES scores (>30) were more frequently observed in patients with epilepsy and PNES (53%) than in patients with epilepsy without PNES (12%) and nonclinical individuals (6%). DES score did not differ significantly with respect to epilepsy-related variables. Neither the frequency nor severity of PNES was significantly associated with the DES score. Our findings confirm some associations between PNES and dissociation in patients with coexisting epilepsy and PNES. The DES could be helpful in determining the tendency to have PNES in patients with epilepsy.

Difference in age of onset of psychosis between epilepsy and schizophrenia.

To clarify the nature of psychosis development in epilepsy patients, we studied differences in age of onset of psychosis between epilepsy patients with psychosis (epilepsy-psychosis) and schizophrenia patients. Subjects were 282 patients with epilepsy-psychosis (36 postictal, 224 interictal, and 22 bimodal psychoses) and 612 schizophrenia patients. Age of onset was compared between the schizophrenia group and the whole epilepsy-psychosis group as well as its subgroups. Effects of sex and family history of psychosis on age of onset were also evaluated. Epilepsy patients developed psychosis later (mean age 30.1) than schizophrenia patients (mean age 26.6). Among epilepsy-psychosis subgroups, postictal psychosis and interictal psychosis showed a later onset than schizophrenia. In interictal psychosis, while chronic schizophrenia-like psychosis occurred at similar age compared to schizophrenia, brief episodic psychosis occurred at later age. Epilepsy-psychosis patients showed no sex difference in age of onset, whereas female schizophrenia patients showed a later onset than male schizophrenia patients. Both the epilepsy and schizophrenia patients with family history of psychosis tended to develop psychosis at an earlier age, although this did not reach statistically significant level. The findings of the study suggest that the nature of epilepsy-psychosis is not fully equivalent to that of schizophrenia.

Association of HLA-A*31:01 Screening With the Incidence of Carbamazepine-Induced Cutaneous Adverse Reactions in a Japanese Population.

Importance: Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated. Objective: To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs. Design, Setting, and Participants: This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016. Exposures: Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. Main Outcomes and Measures: Incidence of carbamazepine-induced cADRs. Results: Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001). Conclusions and Relevance: Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.

Clinical and neuropsychological changes after the disappearance of seizures in a case of transient epileptic amnesia.

We encountered a female patient with late-onset temporal lobe epilepsy who presented with transient amnesia as the sole ictal manifestation, an accelerated rate of forgetting daily life events, and a retrograde memory deficit. We describe the memory function of the patient both before and after the administration of antiseizure medication. After the patient's seizures were controlled with antiseizure drugs, her neuropsychological memory performance scores showed improvement. We presumed that the disappearance of seizures was associated with a decrease in the accelerated rate of forgetting medication. However, her lost memories were not recovered after the seizures were controlled by antiseizure medication.

Automated subfield volumetric analysis of hippocampus in temporal lobe epilepsy using high-resolution T2-weighed MR imaging.

BACKGROUND AND PURPOSE: Automated subfield volumetry of hippocampus is desirable for use in temporal lobe epilepsy (TLE), but its utility has not been established. Automatic segmentation of hippocampal subfields (ASHS) and the new version of FreeSurfer software (ver.6.0) using high-resolution T2-weighted MR imaging are candidates for this volumetry. The aim of this study was to evaluate hippocampal subfields in TLE patients using ASHS as well as the old and new versions of FreeSurfer. MATERIALS AND METHODS: We recruited 50 consecutive unilateral TLE patients including 25 with hippocampal sclerosis (TLE-HS) and 25 without obvious etiology (TLE-nonHS). All patients and 45 healthy controls underwent high-resolution T2-weighted and 3D-volume T1-weighted MRI scanning. We analyzed all of their MR images by FreeSurfer ver.5.3, ver.6.0 and ASHS. For each subfield, normalized z-scores were calculated and compared among groups. RESULTS: In TLE-HS groups, ASHS and FreeSurfer ver.6.0 revealed maximal z-scores in ipsilateral cornu ammonis (CA) 1, CA4 and dentate gyrus (DG), whereas in FreeSurfer ver.5.3 ipsilateral subiculum showed maximal z-scores. In TLE-nonHS group, there was no significant volume reduction by either ASHS or FreeSurfer. CONCLUSIONS: ASHS and the new version of FreeSurfer may have an advantage in compatibility with existing histopathological knowledge in TLE patients with HS compared to the old version of FreeSurfer (ver.5.3), although further investigations with pathological findings and/or surgical outcomes are desirable.