Guideline for evaluating the effects of psychotropic drugs on motor vehicle driving performance in Japan: A tiered approach for the assessment of clinically meaningful driving impairment.

In December 2022, the Ministry of Health, Labour and Welfare (MHLW) of Japan issued and implemented the guideline for evaluating the effects of psychotropic drugs on motor vehicle driving performance. This guideline recommends the use of a tiered approach to assess clinically meaningful driving impairment. It is noted that adverse events cannot be solely explained by pharmacokinetics, as the onset and duration of these events vary. Among these adverse events, those affecting alertness, such as drowsiness caused by psychotropic drugs on driving performance, are more frequently observed during initial treatment stages and dose escalation. Hence, when evaluating the effects of psychotropic drugs on driving performance, it becomes crucial to assess the persistence of clinically meaningful impairment. Therefore, the MHLW guideline, developed by the authors, emphasizes the need to assess the temporal profile of adverse events affecting driving in all clinical trials. Additionally, the guideline states that when conducting driving studies, the timing of multiple dosing should consider not only the pharmacokinetics of the investigational drug but also its tolerance.

Pre-emptive ice pack cryotherapy for reducing pain caused by long-acting deltoid injectable antipsychotic treatment: A single-center open-label study.

PURPOSE: This empirical study aims to investigate the efficacy of pre-emptive cryotherapy in reducing pain that is caused by the deltoid intramuscular (IM) injection of long-acting injectable (LAI) antipsychotics in clinical settings. PATIENTS AND METHODS: This study included 29 outpatients receiving LAI antipsychotic treatment. The evaluations of pain during (1) the usual procedure (control), (2) pre-emptive use of ice pack cryotherapy (pre-cooling), and (3) pre-emptive use of a room-temperature ice pack (pre-touching) were conducted using a numerical rating scale (NRS) for comparison. All patients were administered with LAI antipsychotics via deltoid IM. Furthermore, the results of the Positive and Negative Symptom Scale (PANSS), clinical global impressions (CGI) scale, and Global Assessment of Functioning (GAF) scale that were administered during the control procedure were evaluated. RESULTS: The median NRS pain scores during the IM injection of LAI antipsychotics were 4.0 (3.0-5.0), 2.0 (1.0-3.0), and 3.0 (2.5-6.0) for the control, pre-cooling, and pre-touching conditions, indicating a significant difference (p = 6.0 × 10-6). The NRS pain scores for the pre-cooling condition were significantly lower than those for the control and pre-touching conditions (p = 2.5 × 10-5 and 6.7 × 10-5, respectively). No significant correlation was observed between the NRS pain scores for the control condition and the PANSS, CGI scale, or GAF scale scores. Furthermore, no adverse events were recorded during the study period. CONCLUSION: Pain during the deltoid IM injection of LAI antipsychotics was found to be reduced by pre-emptive skin cooling. To date, this is the first study to confirm the effectiveness of pre-emptive cryotherapy for relieving such pain in clinical situations.

Quetiapine and Valproic Acid-induced Central Hypothyroidism in a Patient with Autism Spectrum Disorder and Intractable Epilepsy: A Case Report.

OBJECTIVES: Patients with an autism spectrum disorder (ASD) are prone to disruptive behaviors and aggression. Atypical antipsychotics are used to treat these difficult ASD conditions. Several psychotropic drugs have been linked to hypothyroidism. The clinical manifestation of hypothyroidism is indistinguishable from that of an antipsychotic's general adverse effect, which can lead to a delayed or missed diagnosis. Conversely, thyroid dysfunction can exhibit an impact on mood, anxiety, depression, and cognitive functions. CASE STUDY: We present a case of central hypothyroidism caused by long-term use of valproic acid (VPA) and adding quetiapine to risperidone. The current case had a history of hyperprolactinemia and subclinical hypothyroidism caused by risperidone and VPA, respectively, before the administration of quetiapine. CONCLUSION: This is the first report of quetiapine-induced central hypothyroidism in a patient with ASD, as determined by a thyrotropin-releasing hormone (TRH) loading test. TRH loading test may be useful in elucidating the pathogenesis of hypothyroidism in patients receiving quetiapine and VPA. Thyroid function monitoring in patients taking quetiapine and VPA may provide an opportunity to begin replacement therapy.

The new guideline for evaluating effects of psychotropic drugs on the performance to drive a motor vehicle in Japan: Comparison with US FDA guideline.

In December 2022, the new guideline for evaluating the effect of psychotropic drugs on the performance to drive a motor vehicle was issued by the Ministry of Health, Labour and Welfare (MHLW) and implemented in Japan. Of the safety information, information on the influence of medications on driving performance is particularly important because it can be relevant to the social functioning of patients. In principle, the package inserts of medications are designed based on evidence and provide precautions regarding the operation of heavy machinery such as automobiles in Japan, the United States, and Europe. The effects of medications on driving performance are generally evaluated in a tiered approach involving nonclinical and clinical studies. Because of the wide variety of functional domains involved in automobile driving, the selection of evaluation methods for a given medication depends on their characteristics, which is a complicated method. Therefore, to evaluate the effects of psychotropic drugs on driving performance efficiently and appropriately, we developed the MHLW guideline that specifically defines the evaluation methods used in pharmacological studies, the neuropsychological tests used in pharmacodynamic studies, and the situations in which driving studies are necessary. Regarding the planning of appropriate drug development strategies, we review the background of the MHLW guideline and its differences from the US Food and Drug Administration (FDA) guideline.

Are brain MRI abnormalities associated with the semiology of functional seizures?

PURPOSE: To investigate whether radiologically apparent brain magnetic resonance imaging (MRI) abnormalities are associated with the functional seizure (FS) semiology. METHODS: All patients with a diagnosis of FS at the epilepsy centers at Shiraz University of Medical Sciences, Iran; Aichi Medical University Hospital, Japan; University of Michigan, USA; University of California, Los Angeles, USA; Emory University School of Medicine, USA; and Hospital el Cruce, Argentina, were studied. RESULTS: One hundred patients were included; 77 (77%) had motor functional seizures. Lobar location of brain abnormality did not have an association with the semiology (p = .83). There was no significant difference between ictal behaviors in patients with frontal or parietal lesions compared to those with temporal or occipital lesions. CONCLUSION: There were no associations between functional seizure ictal behaviors and locations of the radiologically apparent brain MRI abnormalities. Further studies are needed to evaluate the underpinnings of varying behaviors in FS.

Prospective multicenter cohort study of possible psychogenic nonepileptic seizure cases-Results at 1-year follow-up examinations.

OBJECTIVE: The primary purpose of this prospective multicenter study was to examine clinical and demographic feature differences according to the diagnostic level of psychogenic nonepileptic seizures (PNES) and then clarify whether prognosis may also differ accordingly. METHODS: Two hundred forty-two consecutive patients strongly suspected of having PNES attacks were invited to participate, of whom 52 did not consent or contact was lost. At the 1-year follow-up examination, PNES diagnosis was reconsidered in nine patients. In 96 patients, the diagnostic level remained the same (P-group), with that in 43 considered to be clinically established (CE-group) and in 42 documented (D-group). The Qolie-10 and NDDI-E questionnaires were examined at both the study entry and the follow-up examination. RESULTS: Multiple regression analysis of quality of life (QoL) score (n = 173; R2  = 0.374; F = 7.349; P < 0.001) revealed NDDI-E score (t = -6.402; P < 0.001), age of PNES onset (t = -3.026; P = 0.003), and ethnic minority status (t = 3.068; P = 0.003) as significant contributors. At entry, the P-group showed the lowest PNES attack frequency (P < 0.000), the lowest rate of antiseizure, antidepressant, and antipsychotic medication (P < 0.000; P = 0.031; P = 0.013, respectively), and the lowest proportion of psychosis (P = 0.046). At follow-up, PNES attack frequency (P < 0.000), number of admittances to emergency room (P < 0.000), and scores for QoL (P < 0.000) as well as depression (P = 0.004) were found to be significantly improved together with other collateral indicators, such as rate of antiseizure medication prescription (P = 0.001) and psychiatric symptoms (P = 0.03). Multiple regression analysis of a sample limited to patients with intellectual disability (ID) (n = 44; R2  = 0.366; F = 4.493; P = 0.002) revealed continued psychotherapy at follow-up (t = 2.610, P = 0.013) and successful reduction in antiseizure medication (t = 2.868; P = 0.007) as positively related with improved QoL. SIGNIFICANCE: Clinical and the socio-psychological constellation of possible, clinically established, and documented PNES were found to differ greatly. Unexpectedly, significant effects of the continuous psychotherapeutic intervention were confirmed in PNES patients with ID.

Mechanisms of Short- and Long-Latency Sensory Suppression: Magnetoencephalography Study.

Prepulse inhibition (PPI) is sensory suppression whose mechanism (i.e., whether PPI originates from specific inhibitory mechanisms) remains unclear. In this study, we applied the combination of short-latency PPI and long-latency paired pulse suppression in 17 healthy subjects using magnetoencephalography to investigate the mechanisms of sensory suppression. Repeats of a 25-ms pure tone without a blank at 800 Hz and 70 dB were used for a total duration of 1600 ms. To elicit change-related cortical responses, the sound pressure of two consecutive tones in this series at 1300 ms was increased to 80 dB (Test). For the conditioning stimuli, the sound pressure was increased to 73 dB at 1250 ms (Pre 1) and 80 dB at 700 ms (Pre 2). Six stimuli were randomly presented as follows: (1) Test alone, (2) Pre 1 alone, (3) Pre 1 + Test, (4) Pre 2 + Test, (5) Pre 2 + Pre 1, and (6) Pre 2 + Pre 1 + Test. The inhibitory effects of the conditioning stimuli were evaluated using N100m/P200m components. The results showed that both Pre 1 and Pre 2 significantly suppressed the Test response. Moreover, the inhibitory effects of Pre 1 and Pre 2 were additive. However, when both prepulses were present, Pre 2 significantly suppressed the Pre 1 response, suggesting that the Pre 1 response amplitude was not a determining factor for the degree of suppression. These results suggested that the suppression originated from a specific inhibitory circuit independent of the excitatory pathway.

Relationship of loudness-dependent auditory evoked potentials with change-related cortical responses.

Previous studies have suggested that change-related cortical responses are phenomena similar to the onset response and could be applied to the loudness dependence of auditory evoked potential (LDAEP) paradigm. In the present study, we examined the relationship between LDAEP and the change-related response using electroencephalography findings in 50 healthy subjects. There were five conditions (55, 65, 75, 85, and 95 dB) for LDAEP and five similar conditions (abrupt sound pressure increase from 70 to 75, 80, 85, 90, and 95 dB) for the change-related response. Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms. We calculated the peak-to-peak amplitudes for P50/N100 and N100/P200. Medians and slopes for P50/N100 and N100/P200 amplitudes were calculated and compared between the two measures. Results revealed a significant correlation for both the slope and median for P50/N100 (r = 0.36, 0.37, p = 1.0 × 10-2, 7.9 × 10-3), N100/P200 (r = 0.40, 0.34, p = 4.0 × 10-3, 1.6 × 10-2), and P50/N100/P200 (r = 0.36, 0.35, p = 1.0 × 10-2, 1.3 × 10-2). These results suggested that the change-related response and LDAEP shared generation mechanisms at least partially.

Long-lasting leukocytosis in patients with schizophrenia treated with clozapine after electroconvulsive therapy : ECT stabilizes white blood cell count.

INTRODUCTION: The present study was conducted to investigate the possible hematologic impact of long-term electroconvulsive therapy (ECT) in patients with drug-resistant schizophrenia and receiving clozapine therapy. SUBJECTS AND METHODS: In this retrospective study, clinical charts of 57 hospitalized patients with schizophrenia who required clozapine therapy because of active psychotic symptoms resistant to other antipsychotics were examined. For 18 who underwent ECT, the first assessment was conducted at the end of that therapy (average two months after start, 7.68 sessions) and the second two months later. As for the 39 patients who did not undergo ECT, the first and second assessment points were at two and four months, respectively, after a randomly chosen time point. RESULTS: Multiple regression analysis revealed that modified ECT (m-ECT) (ß = 0.346, p = 0.005), gender (males showed greater increase) (ß = 0.273, p = 0.023), and disease duration (longer associated with greater increase) (ß = 0.258, p = 0.033) were correlated with a change in white blood cell (WBC) count (ΔR2 = 0.277, p < 0.001) at the first assessment point. At the second assessment point, multiple regression analysis showed that m-ECT (ß = 0.262, p = 0.039), gender (males showed greater increase) (ß = 0.264, p = 0.036), and disease duration (longer associated with greater increase) (ß = 0.234, p = 0.068) were again correlated with changed WBC count (ΔR2 = 0.203, p < 0.007). DISCUSSION: An increase in leukocytes may have a protective influence against the adverse myelosuppressive effects of clozapine. However, a simple mobilization of leukocytes from bone marrow to peripheral circulation may not enhance the immune system, leading to only a masking of the effects of a potential immuno-insufficient state in the treated patient. In either case, should leukocytosis be induced and then remain for an extended period, hematologists, as well as psychiatrists involved in electroconvulsive intervention for clozapine-treated patients, must keep this factor in mind.

[Optimal Use of Perampanel in the Treatment of Patients with Epilepsy Based on the Clinical Evidence and Characteristics].

Perampanel (PER) has been used clinically as monotherapy and adjunctive therapy for focal seizures and as adjunctive therapy for generalized tonic-clonic seizures in epilepsy patients in Japan. In recent years in Japan and worldwide, clinical studies have been conducted on patients with various seizure types of epilepsy. The results have shown that PER has broad spectrum properties. The pooled analysis of controlled trials (PERMIT study) showed PER efficacy in patients with status epilepticus, myoclonic seizures, and absence seizures. In addition, PER has been shown to be safe and effective in patients with juvenile myoclonic epilepsy, Lennox-Gastaut syndrome, and elderly-onset epilepsy that are often difficult to treat with narrow-spectrum ASM. In this review article, we summarize the latest findings on PER, and overview the broad spectrum characteristics of PER. In addition, we discuss the optimal use of PER for patients with epilepsy, focusing on low-dose initiation and on slow titration of PER to minimize adverse events. (Received December 7, 2021; Accepted March 29, 2022; Published July 1, 2022).

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Quality of life for patients with psychogenic nonepilepsy seizures in comparison with age- and gender-matched patients with epilepsy - Cross-sectional study.

AIMS: Patients with psychogenic nonepileptic seizures (PNES), and age- and gender-matched patients with epilepsy (PWE) who utilized an out-patient service were compared regarding quality of life (QoL) and self-reported symptoms of depression. Additionally, the impact of miscellaneous clinical variables including symptoms of depression on QoL in patients with PNES and PWE in real-world settings was assessed. SUBJECTS AND METHODS: Adult patients who had a diagnosis of definite or documented PNES based on LaFrance's criteria (PNES group, n = 62), or of epilepsy based on results of clinical and EEG procedures (Epilepsy group, n = 61) were enrolled. To assess QoL and evaluate depression, the Quality of Life in Epilepsy Inventory-10 (QOLIE-10) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), respectively, were administered. RESULTS: Comparisons between the groups revealed a shorter duration of illness and fewer number of attacks in patients with PNES as compared to the Epilepsy group (p < 0.0001; p = 0.0003, respectively). There was no significant difference between the groups revealed by the QOLIE-10 (p = 0.141), while the patients with PNES tended to have higher NDDI-E scores (p = 0.068). Multiple regression analysis of QOLIE-10 results in the PNES group revealed that NDDI-E score was the sole significant contributor (ß = -0.425 p = 0.001). In contrast, NDDI-E score as well as attack frequency had a significant impact on QOLIE-10 results in the Epilepsy group (ß = -0.283 p = 0.026; ß = -0.272 p = 0.031, respectively). CONCLUSION: In PWE and patients with PNES who utilized an out-patient service, QoL did not differ significantly between those groups. For treating PNES, psychosocial factors may be a more appropriate indicator of therapeutic goal than attack frequency.

ILAE clinical practice recommendations for the medical treatment of depression in adults with epilepsy.

The aim of this document is to provide evidence-based recommendations for the medical treatment of depression in adults with epilepsy. The working group consisted of members of an ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Psychiatry, ILAE Executive and the International Bureau for Epilepsy (IBE) representatives. The development of these recommendations is based on a systematic review of studies on the treatment of depression in adults with epilepsy, and a formal adaptation process of existing guidelines and recommendations of treatment of depression outside epilepsy using the ADAPTE process. The systematic review identified 11 studies on drug treatments (788 participants, class of evidence III and IV); 13 studies on psychological treatments (998 participants, class of evidence II, III and IV); and 2 studies comparing sertraline with cognitive behavioral therapy (CBT; 155 participants, class of evidence I and IV). The ADAPTE process identified the World Federation of Societies of Biological Psychiatry guidelines for the biological treatment of unipolar depression as the starting point for the adaptation process. This document focuses on first-line drug treatment, inadequate response to first-line antidepressant treatment, and duration of such treatment and augmentation strategies within the broader context of electroconvulsive therapy, psychological, and other treatments. For mild depressive episodes, psychological interventions are first-line treatments, and where medication is used, selective serotonin reuptake inhibitors (SSRIs) are first-choice medications (Level B). SSRIs remain the first-choice medications (Level B) for moderate to severe depressive episodes; however, in patients who are partially or non-responding to first-line treatment, switching to venlafaxine appears legitimate (Level C). Antidepressant treatment should be maintained for at least 6 months following remission from a first depressive episode but it should be prolonged to 9 months in patients with a history of previous episodes and should continue even longer in severe depression or in cases of residual symptomatology until such symptoms have subsided.

Mechanisms of Long-Latency Paired Pulse Suppression: MEG Study.

Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway.

Psychotic Disorders in Epilepsy: Do They Differ from Primary Psychosis?

Any attempt to compare the definitions of symptoms listed for "primary psychoses" with those adopted in studies of psychoses in patients with epilepsy (PWE) will encounter problems of heterogeneity within both conditions. In this manuscript, five psychotic illnesses listed in Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5), that is, brief psychotic illness, schizophreniform disorder, schizophrenia, delusional disorder, and schizoaffective disorder are compared with postictal (or periictal) and interictal psychotic disorders in PWE. After examining definitions of primary psychoses, definitions of psychoses adopted in the papers dealing with postictal and interictal psychoses are summarized. Further, diagnostic criteria of five types of psychotic disorders in PWE proposed in 2007 by Krishnamoorthy et al. are also discussed, which include postictal psychosis, comorbid schizophrenia, iatrogenic psychosis caused by antiepileptic drugs (AEDs) (AED-induced psychotic disorder: AIPD), and forced normalization. Evidently, a comparison between postictal psychosis and schizophrenia is pointless. Likewise, schizophrenia may not be an appropriate counterpart of forced normalization and AIPD, given their acute or subacute course.Based on these preliminary examinations, three questions are selected to compare primary psychoses and psychoses in PWE: Is postictal psychosis different from a brief psychotic disorder? Does epilepsy facilitate or prevent the development of psychosis or vice versa? Is interictal psychosis of epilepsy different from process schizophrenia? In conclusion, antagonism between psychosis and epileptic seizures in a later stage of active epilepsy seems not to be realized without reorganization of the nervous system promoted during an earlier stage. Both genetic predisposition and the summated effects of epileptic activity must be taken into consideration as part of a trial to explain interictal psychosis. Interictal psychosis is an aggregate of miscellaneous disorders, that is, co-morbid schizophrenia, AED-induced psychotic disorders, forced normalization, and "epileptic" interictal psychosis. Data are lacking to conclude whether differences exist between process schizophrenia and "epileptic" interictal psychosis in terms of negative symptoms, specific personal traits, and the "bizarre-ness" of delusory-hallucinatory contents. These discussions may shed light on the essence of process schizophrenia, thus allowing it stand out and receive increased focus.

Functional (psychogenic non-epileptic/dissociative) seizures: why and how?

Functional seizures (FS) known also as psychogenic non-epileptic seizures or dissociative seizures, present with ictal semiological manifestations, along with various comorbid neurological and psychological disorders. Terminology inconsistencies and discrepancies in nomenclatures of FS may reflect limitations in understanding the neuropsychiatric intricacies of this disorder. Psychological and neurobiological processes of FS are incompletely understood. Nevertheless, important advances have been made on underlying neuropsychopathophysiological mechanisms of FS. These advances provide valuable information about the underlying mechanisms of mind-body interactions. From this perspective, this narrative review summarises recent studies about aetiopathogenesis of FS at two levels: possible risk factors (why) and different aetiopathogenic models of FS (how). We divided possible risk factors for FS into three categories, namely neurobiological, psychological and cognitive risk factors. We also presented different models of FS based on psychological and neuroanatomical understanding, multilevel models and integrative understanding of FS. This work should help professionals to better understand current views on the multifactorial mechanisms involved in the development of FS. Shedding light on the different FS profiles in terms of aetiopathogenesis will help guide how best to direct therapy, based on these different underlying mechanisms.

Differences in aggression as psychiatric side effect of levetiracetam and perampanel in patients with epilepsy.

PURPOSE: Aggression is the most commonly encountered antiepileptic-drug (AED)-induced psychiatric adverse effects. Levetiracetam (LEV) is well known to be associated with increased rates of aggression, while perampanel (PER) is also recognized as a potentially aggression-promoting agent, though opinions vary. However, few studies have addressed questions regarding whether the nature of irritability-aggression differs between those drugs. The present study used a standardized rating scale to examine aggression among patient with epilepsy who received LEV or PER using specific measures to confirm the effects of the drugs. METHODS: We enrolled 144 consecutive outpatients receiving treatment for epilepsy with LEV (n = 103) or PER (n = 41), and determined their effects regarding aggression using the Buss-Perry Aggression Questionnaire (BAQ). For analysis, total BAQ scores for the LEV and PER subjects were compared to determine whether the aggression-promoting effects of the agents differed, and which BAQ subdomains (physical aggression, verbal aggression, anger, hostility) were related to production of aggression in patients taking either LEV or PER. As a subsidiary analysis, clinical variables inclusive of administered AED type that showed a significant impact on BAQ scores were determined. RESULTS: The LEV group had a significantly higher hostility score (19.4 ±â€¯5.8) as compared to the PER group (17.2 ±â€¯6.3) in subscale analysis (p < 0.05). In multiple regression analysis, LEV had a significant association with higher hostility score (P = 0.006). CONCLUSION: Our results indicate that while easily visible outward-directed aggression tends to be dominant in patients given PER, aggression provoked by LEV may be felt more subjectively or in an inward-directed manner, which can lead to more diverse expression and misrecognition.

Clinical features of catatonic non-convulsive status epilepticus: A systematic review of cases.

OBJECTIVE: Non-convulsive status epilepticus (NCSE) can manifest as catatonia, although it is unclear how frequently such cases have been reported. The common clinical features of these two conditions are also unclear. METHODS: Using the MEDLINE and Embase databases, we performed a systematic literature search to identify cases diagnosed with both catatonia, according to the Bush-Francis Catatonia Rating Scale, and NCSE, according to the Salzburg Consensus Criteria (last search: March 29, 2021). We extracted data on demographics, clinical features of catatonia, EEG findings, and treatments. RESULTS: A total of 66 patients with catatonic NSCE (men, 49%; mean age, 42.0 years) were identified from our search. Of the 66 cases described: 30 (46%) showed motor symptoms; 35 (38%) occurred in patients with preceding episodes of epileptic seizures; 19 (29%) showed subtle ictal clinical phenomena, such as minor twitching of the mouth, periorbital region, and extremities; 22 (33%) presented with psychiatric symptoms prior to the onset of catatonia; 17 (26%) had a history of psychiatric diseases; and in 10 cases (15%), NSCE was confirmed by intentional or non-intentional long-term EEG monitoring. Benzodiazepines were used as the initial treatment for NCSE in 30 cases (49%), of which 20 cases (73%) improved with monotherapy. DISCUSSION: A substantial number of cases included in the present review involved catatonia without any symptoms indicative of epilepsy, suggesting that NCSE may be misdiagnosed as a psychiatric disease, and highlighting the importance of the accurate diagnosis and treatment of NCSE in patients presenting with catatonia.

Impact of antiepileptic drugs on simulated driving in patients with epilepsy.

OBJECTIVE: Results of observational investigations have demonstrated that the risk of a traffic accident is independent of use of AEDs. However, no reports of driving tests conducted with patients administered AEDs have been presented. This study examined this scenario in a simulated driving setting. METHODS: Driving performance of 43 patients with epilepsy (PWE) and prescribed an AED, who were licensed to drive and drove regularly (subject group), was assessed, with the results compared to 40 age- and gender-matched healthy volunteers (control group). Daily driving skills associated with a traffic accident were examined using two different tests provided by a driving simulator software package, road-tracking and car-following. Standard deviation of lateral position (SDLP) and distance coefficient of variation (DCV) were determined as primary and exploratory outcomes, respectively. RESULTS: There was no statistically significant difference for primary outcome shown by SDLP between the subject and control groups (p = 0.906), nor for exploratory outcome shown by DCV (p = 0.063). Multiple regression analysis revealed that age (ß=0.967, p = 0.001), female gender (ß=0.469, p<0.001), and duration of driving experience (ß=-0.583, p = 0.038) were correlated with SDLP. SIGNIFICANCE: The present results demonstrated that the driving performance of PWE taking AEDs was not different from that of healthy volunteers.

Use of suggestive seizure manipulation methods in the investigation of patients with possible psychogenic nonepileptic seizures-An international ILAE survey.

Video-encephalographic (vEEG) seizure recordings make essential contributions to the differentiation of epilepsy and psychogenic nonepileptic seizures (PNES). The yield of vEEG examinations can be increased through suggestive seizure manipulation (SSM) (ie, activation/provocation/cessation procedures), but its use has raised ethical concerns. In preparation for guidelines on the investigation of patients with PNES, the ILAE PNES Task Force carried out an international survey to investigate practices of and opinions about SSM. An online questionnaire was developed by the ILAE PNES Task Force. Questions were asked at clinical unit or individual respondent level. All ILAE chapters were encouraged to send questionnaires to their members. The survey was open from July 1, 2019, to August 31, 2019. A total of 487 clinicians from 411 units across 94 countries responded. Some form of SSM was used in 296/411 units (72.0%). Over 90% reported the use of verbal suggestion, over 80% the use of activation procedures also capable of eliciting epileptic activity (hyperventilation or photic stimulation). Only 26.3% of units used techniques specifically intended to provoke PNES (eg, saline injection). Fewer than 10% of units had established protocols for SSM, only 20% of units required written patient consent, in 12.2% of units patients received explicitly false information to provoke seizures. Clinicians using SSM tended to perceive no ethical problems, whereas those not using SSM were likely to have ethical concerns about these methods. We conclude that the use of invasive nocebo techniques intended to provoke PNES in diagnostic settings has declined, but SSM is commonly combined with activation procedures also capable of eliciting epileptic activity. While research suggests that openness about the use of PNES-specific nocebo techniques does not reduce diagnostic yield, very few units have suggestion protocols or seek patient consent. This could be addressed through establishing consensus guidance for the practice of SSM.