The Role of Autophagy and Apoptosis in Neuropathic Pain Formation.

Neuropathic pain indicates pain caused by damage to the somatosensory system and is difficult to manage and treat. A new treatment strategy urgently needs to be developed. Both autophagy and apoptosis are critical adaptive mechanisms when neurons encounter stress or damage. Recent studies have shown that, after nerve damage, both autophagic and apoptotic activities in the injured nerve, dorsal root ganglia, and spinal dorsal horn change over time. Many studies have shown that upregulated autophagic activities may help myelin clearance, promote nerve regeneration, and attenuate pain behavior. On the other hand, there is no direct evidence that the inhibition of apoptotic activities in the injured neurons can attenuate pain behavior. Most studies have only shown that agents can simultaneously attenuate pain behavior and inhibit apoptotic activities in the injured dorsal root ganglia. Autophagy and apoptosis can crosstalk with each other through various proteins and proinflammatory cytokine expressions. Proinflammatory cytokines can promote both autophagic/apoptotic activities and neuropathic pain formation, whereas autophagy can inhibit proinflammatory cytokine activities and further attenuate pain behaviors. Thus, agents that can enhance autophagic activities but suppress apoptotic activities on the injured nerve and dorsal root ganglia can treat neuropathic pain. Here, we summarized the evolving changes in apoptotic and autophagic activities in the injured nerve, dorsal root ganglia, spinal cord, and brain after nerve damage. This review may help in further understanding the treatment strategy for neuropathic pain during nerve injury by modulating apoptotic/autophagic activities and proinflammatory cytokines in the nervous system.

Correlations among disability, anti-AQP4 antibody status and prognosis in the spinal cord involved patients with NMOSD.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare neuroinflammatory disorder of the central nervous system that typically involves the optic nerve, the spinal cord and other specific brain regions. In relapse of the disease, factors associated with clinical features and lesion severity are important for clinicians to predict disease-related disability. METHODS: We retrospectively analyzed 22 female patients with NMOSD who had spinal cord lesions. Detailed clinical features, onset symptoms, motor disability, relapse episodes, serum aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) autoantibodies and MRI characteristics were documented to correlate their associations with the nadir and three-month Expanded Disability Status Scale (EDSS) scores. Patients with three-month EDSS scores below four (< 4) were categorized as the good outcome group, while those with scores of four or more (> 4) were categorized as the poor outcome group. RESULTS: In patients with NMOSD, the mean age was 44.5 ± 12.8 years, and the mean three-month EDSS score was 4.3 ± 1.9. A significantly higher all-limb muscle power score was found in the good EDSS group than in the poor EDSS group (p = 0.01). A tendency toward longer follow-up periods and lower anti-AQP4 antibody levels was found in the good outcome group. Serum anti-AQP4 antibodies were present in 86% of patients with NMOSD, and MOG autoantibodies were found in one anti-AQP4 antibody-negative patient (33.3%). In patients with NMOSD, more than 40% of spinal cord lesions were distributed at the middle cervical and upper thoracic levels. CONCLUSIONS: Our findings suggest that EDSS scores and MRC scores at the nadir had significant associations with three-month EDSS scores. The topographic distributions of the spinal cord lesions might relate to different serum anti-AQP4 antibody status. However, further studies will be needed to corroborate this finding.

A prospective, multicenter, noninterventional study in Taiwan to evaluate the safety and tolerability of lacosamide as adjunctive therapy for epilepsy in clinical practice.

RATIONALE: Lacosamide (LCM) was initially approved in Taiwan in March 2014 for use as adjunctive therapy for focal impaired awareness seizures and secondarily generalized seizures (SGS) in patients with epilepsy ≥16 years of age. The efficacy and tolerability of adjunctive LCM for the treatment of patients with focal seizures have been demonstrated in randomized, placebo-controlled trials. However, the trials do not reflect a flexible dose setting. This study (EP0063) was conducted to assess the safety and tolerability of LCM in real-world clinical practice in Taiwan. Effectiveness of LCM was also assessed as an exploratory objective. METHODS: EP0063 was a multicenter, prospective, noninterventional study with an expected observation period of 12 months ±â€¯60 days. Eligible patients were ≥16 years of age, had focal impaired awareness seizures and/or SGS (in line with approved indication in Taiwan at the time of the study), were taking at least one concomitant antiseizure medication (ASM), and had at least one seizure in the 3 months before baseline. Patients were prescribed LCM by their treating physician in the course of routine clinical practice. The primary safety variable was treatment-emergent adverse events (TEAEs) spontaneously reported to, or observed by, the treating physician. Based on safety data from previous studies of LCM and known side effects of other ASMs, certain TEAEs (including but not limited to cardiac and electrocardiogram, suicidality, and rash related terms) were analyzed separately. Effectiveness variables included Clinical Global Impression of Change (CGIC) and change in 28-day seizure frequency from baseline to 12 months (or final visit), and freedom from focal seizures. RESULTS: A total of 171 patients were treated with LCM, of whom 139 (81.3%) completed the study. The Kaplan-Meier estimated 12-month retention was 82.9%. Patients had a mean (standard deviation [SD], range) age of 38.5 (14.0, 16-77) years, and 96 (56.1%) were male. Patients were taking a mean (SD, range) of 2.8 (1.1, 1-6) ASMs at baseline. Mean (SD, range) duration of LCM treatment was 288.7 (111.9, 2-414) days, and the mean (SD, range) daily dosage of LCM was 205.0 (82.7, 50.0-505.2) mg/day. Overall, 95 (55.6%) patients reported at least one TEAE, most commonly dizziness (33 [19.3%] patients). Drug-related TEAEs were reported in 74 (43.3%) patients, and drug-related TEAEs leading to discontinuation of LCM were reported in 14 (8.2%) patients. Two (1.2%) patients died during LCM treatment, which were considered not related to LCM. Two (1.2%) patients had suicidality-related TEAEs; these TEAEs were considered either not related to LCM or the relationship was not recorded. Rash-related TEAEs were reported in five (2.9%) patients (considered LCM-related in two patients). Based on the CGIC, at 12 months (or final visit), 109 (63.7%) patients were considered to have improved, 54 (31.6%) had no change, and the remaining eight (4.7%) were minimally worse. At 12 months (or final visit), the median percentage change in focal seizure frequency was -50.0. During the first 6 months of the study, 21 (12.3%) patients were free from focal seizures; 37 (21.6%) patients were free from focal seizures in the last 6 months of the study; and 14 (8.2%) were free from focal seizures for the full 12 months of the study. CONCLUSIONS: Results of this prospective, noninterventional study suggest that adjunctive LCM was generally safe and well tolerated in this patient group in real-world practice in Taiwan. Effectiveness was also favorable, with more than 60% of patients considered to be improved by their physician at 12 months (or final visit).

Electrical cortical stimulation for treatment of intractable epilepsy originating from eloquent cortex: surgical accuracy and clinical efficacy.

BACKGROUND: Electrical cortical stimulation is shown effective in treating patients with drug-resistant epilepsy. We demonstrated how detailed procedures of pre- and intra-operative planning of cortical stimulation implantation may influence the results of seizure reduction rate. METHODS: To confirm the precision of subdural grids covering the epileptogenic foci in the eloquent regions, pre- and intra-operative video-electroencephalography (VEEG) were performed in patients with drug-resistant epilepsy during a 4-day 24-h monitoring. The localization of the grid was determined via 3D reconstruction imaging of subdural electrodes co-registered onto the patient's cortex. A final quadripolar lead in cyclic stimulation mode was then placed and secured on the target cortex area. Post-operative 3D CT ensured the accurate location of stimulation lead without any misplacement. Bipolar cyclic stimulation and post-implantation VEEG were performed for 7 days. Patients were discharged and followed up regularly for parameters adjustment and recording of seizure outcomes. RESULTS: Eight patients received chronic cortical stimulation implantations between February 2003 and December 2017. The mean age of these patients was 21.1 years old and the average post-operative follow-up was 77.3 months. Comparisons of their seizure frequency at baseline and during the postoperative period revealed a mean reduction in seizures of 60.4% at the first year and 65.6% at the second year. CONCLUSIONS: Pre-surgical planning enhanced the accuracy of electrode placement and led to a favorable seizure reduction rate. Our report confirms that electrical cortical stimulation with detailed implantation procedures is safe and effective for patients with drug-resistant epilepsy originating from eloquent cortex.

Clinical, Electroencephalographic Features and Prognostic Factors of Cefepime-Induced Neurotoxicity: A Retrospective Study.

BACKGROUND: The incidence of cefepime-induced neurotoxicity (CIN) has been previously underestimated, and there have only been sporadic reports from critical neurological settings. The present study aimed to investigate the potential factors associated with disease development, electroencephalography (EEG) sub-classification, and outcome measures. METHODS: The 10-year medical records of patients who underwent EEG between 2007 and 2016 at a tertiary medical center in Taiwan, and developed encephalopathy after cefepime therapy were retrospectively reviewed. Age- and sex-matched controls were included for further analysis. Demographic data, the occurrence of clinical seizures, non-convulsive status epilepticus (NCSE), use of antiepileptic drugs (AEDs), receiving maintenance or urgent hemodialysis, EEG findings, and functional outcomes were analyzed. The Chi-square test and a logistic regression model were applied to survey significant prognostic factors relating to mortality. RESULTS: A total of 42 CIN patients were identified, including 25 patients from wards and 17 from intensive care units; their mean age was 75.8 ± 11.8 years. Twenty-one patients (50%) had chronic kidney disease, and 18 (43%) had acute kidney injury. Among these patients, 32 (76%) received appropriate cefepime dose adjustment. Three patients had a normal renal function at the time of CIN onset. The logistic regression model suggested that maintenance hemodialysis and longer duration of cefepime use were independently associated with the development of CIN, with odds ratios of 3.8 and 1.2, respectively. NCSE was frequently noted in the CIN patients (64%). Generalized periodic discharge with or without triphasic morphology was the most common EEG pattern (38%), followed by generalized rhythmic delta activity and generalized spike-and-waves. AEDs were administered to 86% of the patients. A total of 17 patients (40%) did not survive to hospital discharge. Adequate cefepime dose adjustment and early cefepime discontinuation led to a better prognosis. CONCLUSIONS: CIN was associated with high mortality and morbidity rates. Neurotoxic symptoms could still occur when the cefepime dose was adjusted, or in patients with normal renal function. Patients with maintenance hemodialysis or a longer duration of cefepime therapy tended to develop CIN. Early recognition of abnormal EEG findings allowed for the withdrawal of the offending agent, resulting in clinical improvements and a better prognosis at discharge.

A compartmentalized culture device for studying the axons of CNS neurons.

We report here the development of a compartmentalized culture device that allows the spatial separation of the somatodendrites and axons of central nervous system (CNS) neurons. The device consists of two compartments separated by a septum constructed by attaching a porous polycarbonate track etch (PCTE) filter on top of a microchannel-filled polydimethylsiloxane (PDMS) membrane. The surface and microchannels of the septum are coated and filled, respectively, with materials that support neuron growth and neurite migration. When rat hippocampal neurons are cultured in the top compartment, axons are the only processes that can migrate through the septum to the bottom compartment. The axons in the bottom compartment can be studied directly in real-time or through immunofluorescence staining after fixation. Axons containing ∼3 µg protein can be isolated from each device for biochemical analyses. In addition, the septum also impedes the movement of small molecules between the top and bottom compartments. This feature allows the somatodendrites and axons of neurons, which occupy the top and bottom compartments of the device, respectively, to be manipulated independently. The potential applications of the device as a tool in diverse studies concerning neuronal axons and in screening reagents that regulate axonal functions have also been discussed.

Status epilepticus associated with pregnancy: A cohort study.

BACKGROUND: Status epilepticus (SE) is a neurological emergency associated with a high mortality rate and long-term cognitive sequelae. Status epilepticus in pregnancy poses a tremendous threat to both mother and fetus, making a correct diagnosis and treatment a challenging task for clinicians. The prevalence, underlying etiology, and outcomes of pregnancy-related SE remain largely unknown. METHODS: We retrospectively studied all SE episodes (n=366) in patients admitted to our neurological ICU over a period of 8.5years. The patients who developed SE during pregnancy and within 6months after delivery were considered to have pregnancy-related SE. Patients with eclampsia were not included as they were usually cared for in our obstetric unit. RESULTS: Seven patients with pregnancy-related SE were identified (2.1% of all cases of SE), with the majority (85%) occurring de novo except for one patient who had a previous history of epilepsy-related SE due to withdrawal of antiepileptic medication. In terms of etiology, limbic encephalitis and cerebral venous sinus thrombosis were the two main etiologies of de novo SE associated with pregnancy. The overall mortality rate was 28.5% at discharge, and poor outcomes were especially noted in the patients with limbic encephalitis compared to other etiologies. CONCLUSIONS: Pregnancy-associated SE is rare and predominantly occurs in patients without a history of epilepsy. An autoimmune etiology should be considered in pregnant patients with de novo SE, which was associated with poor outcomes. Thorough investigations and prompt treatment according to the etiology may be required to improve the final outcomes of both mother and fetus.

Low and High Frequency Hippocampal Stimulation for Drug-Resistant Mesial Temporal Lobe Epilepsy.

OBJECTIVE: Electrical stimulation of the hippocampus offers the possibility to treat patients with mesial temporal lobe epilepsy (MTLE) who are not surgical candidates. We report long-term follow-up results in five patients receiving low or high frequency hippocampal stimulation for drug-resistant MTLE. MATERIALS AND METHODS: The patients underwent stereotactic implantation of quadripolar stimulating electrodes in the hippocampus. Two of the patients received unilateral electrode implantation, while the other three received bilateral implantation. Stimulation of the hippocampal electrodes was turned ON immediately after the implantation of an implantable pulse generator, with initial stimulation parameters: 1 V, 90-150 µs, 5 or 145 Hz. The frequency of seizures was monitored and compared with preimplantation baseline data. RESULTS: Two men and three women, aged 27-61 years were studied, with a mean follow-up period of 38.4 months (range, 30-42 months). The baseline seizure frequency was 2.0-15.3/month. The five patients had an average 45% (range 22-72%) reduction in the frequency of seizures after hippocampal stimulation over the study period. Low frequency hippocampal stimulation decreased the frequency of seizures in two patients (by 54% and 72%, respectively). No implantation- or stimulation-related side effects were reported. CONCLUSIONS: Electrical stimulation of the hippocampus is a minimally invasive and reversible method that can improve seizure outcomes in patients with drug-resistant MTLE. The optimal frequency of stimulation varied from patient to patient and therefore required individual setting. These experimental results warrant further controlled studies with a large patient population to evaluate the long-term effect of hippocampal stimulation with different stimulation parameters.

Clinical Research into Central Nervous System Inflammatory Demyelinating Diseases Related to COVID-19 Vaccines.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types.

Impact of comorbidities on relapsing rates of Neuromyelitis Optica Spectrum Disorders: Insights from a longitudinal study in Taiwan.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear. METHODS: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006 to 2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined. RESULTS: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9 %) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26-1.11) for adults and 0.39 (IQR: 0.21-0.77) for pediatric patients. Comorbidities included malignancy (6.7 %) and autoimmune diseases (21.7 %). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities. CONCLUSIONS: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan.

Therapeutic drug monitoring of perampanel: Clinical utility and impact of co-medication on pharmacokinetic variability.

Background: Perampanel (PER) is a newly developed antiseizure medication (ASM). This study aimed to determine the utilization of therapeutic drug monitoring (TDM) for PER in a real-world clinical setting and investigate the influence of concomitant use of ASMs on the plasma concentration profile of PER. Method: We analyzed data from the Chang Gung Research Database, which is the largest multi-institutional electronic medical records database in Taiwan. The main outcomes were the comparisons of PER plasma concentration and the ratio of concentration to the weight-adjusted dose (C/D; [ng/mL]/[mg/kg/d]) among patients received TDM of different clinical indication and among different ASM co-medication subgroups. Results: Overall, 88 plasma samples were collected from 66 epilepsy patients treated with PER. The majority of patients (77.3 %) underwent PER TDM owing to poorly controlled seizures. There was a trend toward a higher plasma concentration and C/D ratio in those suspected of having PER toxicity owing to adverse events than of other indications. The PER concentration exhibited dose linearity. The mean PER plasma concentrations in patients co-medicated with enzyme-inducing ASMs were significantly lower than those in the patients who were not prescribed enzyme-inducing or enzyme-inhibiting ASMs, and co-medication with carbamazepine (CBZ) resulted in a significant reduction in the PER concentration. Conclusion: PER concentration exhibited a linear regression relationship with PER dose, and the plasma concentration of the drug was highly susceptible to the drug's interactions with enzyme-inducing ASMs. TDM with clear indication could help determine the influence of ASMs used concomitantly on PER concentrations and guide clinical adjustments.

Juvenile Myoclonic Epilepsy: Seizure and Social Outcomes in Taiwan.

Patients with juvenile myoclonic epilepsy (JME) may not achieve seizure freedom despite optimal treatment with antiseizure medications (ASMs). The aim of this study was to investigate the clinical and social features of patients with JME, and to determine the factors associated with outcomes. We retrospectively identified 49 patients with JME (25 females, mean age 27.6 ± 8.9 years) who were assessed at the Epilepsy Centre of Linkou Chang Gung Memorial Hospital in Taiwan. The patients were divided into two groups, those who were seizure-free and those with ongoing seizures according to their seizure outcome at the last follow-up for one year. Clinical features and social status were compared between these two groups. Twenty-four (49%) of the JME patients were seizure-free for at least one year, while 51% continued to experience seizures despite being treated with multiple ASMs. The presence of epileptiform discharges in the last electroencephalogram and seizures during sleep were significantly associated with worse seizure outcomes (p < 0.05). The patients who were seizure-free had a higher employment rate compared to those who continued to experience seizures (75% vs. 32%, p = 0.004). Despite receiving ASM treatment, a considerable proportion of the patients with JME continued to have seizures. Moreover, poor seizure control was associated with a lower employment rate, which may lead to negative socioeconomic consequences related to JME.

Clinical impact of therapeutic drug monitoring for newer anti-seizure medications in patients with epilepsy: A real-world observation study.

BACKGROUND: The clinical value of therapeutic drug monitoring (TDM) for newer anti-seizure medications (ASMs) remains uncertain. This study aimed to assess the impact of newer ASM TDM on clinical decision making in patients with epilepsy. METHODS: We retrospectively identified all plasma requests for newer ASM level measurement as part of routine clinical management in the outpatient departments of seven medical institutes across Taiwan between September 2016 and May 2019. Data collected from reviewed medical records included clinical and medication details, indications for TDM request, test results, interpretation, and impact on patient management. RESULTS: A total of 682 visits with 1051 plasma samples were included. The most frequently analyzed ASMs were levetiracetam (36.1%), oxcarbazepine (18.4%), and lamotrigine (12.0%). Reasons for TDM included poorly controlled seizures (55.3%), concerns about drug-drug interactions (12.3%), and suspicion of drug overdose (10.6%). 68.8% of samples were within the orienting therapeutic range, even for patients with poorly controlled seizures. TDM for non-adherence concerns showed 54.3% below the orienting therapeutic range, while ASM-related adverse events assessment only 8.9% showed levels exceeding the orienting therapeutic range. Following TDM results, 64.2% of cases had medication adjustments, mainly dosage increases. Overall, 55.9% of newer ASM TDM visit showed improved outcomes, including reduced seizures (47.5%) and fewer ASM-related side effects (8.4%). CONCLUSIONS: These findings suggest that appropriate utilization of TDM for newer ASMs provides clinical benefits in adjunct to complement clinical decision making in the management of epilepsy patients in a real-world clinical setting.

Long-term Outcome of Seizure Control and Neurologic Performance After Limited Hippocampal Radiofrequency Thermocoagulation for Mesial Temporal Lobe Epilepsy.

OBJECTIVE: Limited hippocampal radiofrequency thermocoagulation (RFTC) for patients with mesial temporal lobe epilepsy was associated with good short-term seizure control and few complications. We aimed to demonstrate the neuropsychologic outcomes and assess the prognostic factors of long-term seizure control in these patients. METHODS: We included all patients with mesial temporal lobe epilepsy who underwent limited hippocampal RFTC from January 2016 to December 2020. Clinical data of age, sex, seizure control before and after operation were all corrected. Pre- and postoperative neuropsychologic function including full-scale intelligence quotient (FSIQ), memory quotient, and the Mini-Mental State Examination was used. RESULTS: Thirty-one patients (17 female and 14 male) with a mean epilepsy duration of 22.3 years and seizure frequency of 5.7 times per month were included. The intraoperative seizure rate was 19.3%, and a higher preoperative seizure frequency (P = 0.001) and longer duration of epilepsy (P = 0.042) were associated with the occurrence of intraoperative seizures. The postoperative FSIQ scores were significantly better than preoperative scores (mean 92.1 vs. 89.7, P = 0.014). Nine patients (29%) who underwent limited hippocampal RFTC were seizure-free at 1 year of follow-up. Responders represented 58% (n = 18) of patients at 1 year. The mean follow-up period was 34.7 ± 13.3 months. Five patients remained seizure free and 13 patients are still responders at the last follow-up visits. Long-term seizure frequency was 2.32 ± 2.86 times per month. CONCLUSIONS: Limited hippocampal RFTC is a safe stereotactic minimal invasive procedure with good neuropsychologic outcome and acceptable efficacy of seizure reduction in appropriately selected patients.

Reduced Sleep Quality Is Related to Poor Quality of Life in Patients with Juvenile Myoclonic Epilepsy, a Case-Control Study.

Juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy which is closely related to the sleep-wake cycle. This study aimed to investigate whether sleep disturbance is more common among patients with JME and the impact this may have on their quality of life (QOL). Thirty-four patients with JME and age- and gender-matched controls were recruited into this case control study, and assessed using validated sleep questionnaires including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Stanford Sleepiness Scale (SSS). QOL was assessed using the Quality of Life in Epilepsy Inventory (QOLIE-31). The patients had a significantly higher PSQI score and higher proportion of abnormal PSQI scores than the controls. They also had higher ESS and SSS scores, but without statistical significance. The patients with poor sleep quality had significantly lower overall QOL, emotional well-being, and energy/fatigue subscale scores. The use of a higher number of antiseizure medications, dosage of levetiracetam, and usage of antiseizure medication polytherapy were associated with sleep disorders. Our results showed that sleep disturbance is common in patients with JME, and also that it has an impact on their QOL.

Robot-Assisted Radiofrequency Ablation Combined with Thermodynamic Simulation for Epilepsy Reoperations.

Repeat craniotomies to treat recurrent seizures may be difficult, and minimally invasive radiofrequency ablation is an alternative therapy. On the basis of this procedure, we aimed to develop a more reliable methodology which is helpful for institutions where real-time image monitoring or electrophysiologic guidance during ablation are not available. We used simulation combined with a robot-assisted radiofrequency ablation (S-RARFA) protocol to plan and execute brain epileptic tissue lesioning. Trajectories of electrodes were planned on the robot system, and time-dependent thermodynamics was simulated with radiofrequency parameters. Thermal gradient and margin were displayed on a computer to calculate ablation volume with a mathematic equation. Actual volume was measured on images after the ablation. This small series included one pediatric and two adult patients. The remnant hippocampus, corpus callosum, and irritative zone around arteriovenous malformation nidus were all treated with S-RARFA. The mean error percentage of the volume ablated between preoperative simulation and postoperative measurement was 2.4 ± 0.7%. No complications or newly developed neurologic deficits presented postoperatively, and the patients had little postoperative pain and short hospital stays. In this pilot study, we preliminarily verified the feasibility and safety of this novel protocol. As an alternative to traditional surgeries or real-time monitoring, S-RARFA served as successful seizure reoperation with high accuracy, minimal collateral damage, and good seizure control.

Treatment of pharmacoresistant sleep-related hypermotor epilepsy (SHE) with the selective AMPA receptor antagonist perampanel.

This study aimed to evaluate the efficacy and tolerability of perampanel (PER) as adjunctive therapy in patients with pharmacoresistant sleep-related hypermotor epilepsy (SHE). Patients diagnosed with SHE who received PER treatment between 2016 and 2019 were included, and their data were reviewed retrospectively. Diagnosis was based on reports of patients or family members witnessing the events and clinical characteristics of seizures captured by video or during video-electroencephalography monitoring. Among 36 SHE patients, 20 with pharmacoresistant SHE (six female; mean age: 34.1 ± 9.0 years) who received PER as adjunctive therapy were included in this study. Fourteen out of the 20 patients received PER with mean length of PER exposure of 24.6 ± 15.7 months: 10 of them were responders and four non-responders. The remaining six patients discontinued PER for adverse events (n = 5) and patient choice (n = 1). Among the 10 responders, six (60%) reported seizure-free periods lasting ≥6 months. The most common PER-associated adverse event was dizziness (25%) followed by malaise (10%). Clinical experience with these patients demonstrated that PER might be considered as an add-on anti-seizure medication for patients with highly pharmacoresistant SHE.

Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review.

BACKGROUND: The effective dose of perampanel in status epilepticus (SE), refractory SE (RSE), and super-refractory SE (SRSE) in humans is unknown, and the potential of perampanel in treating SE has not been evaluated in a large cohort. METHODS: Data of intensive care patients with RSE and SRSE treated with perampanel were retrospectively reviewed and analyzed. RESULTS: Eighty-one patients received perampanel, including 39 females with median age 64 [17-91] years, perampanel responders (n = 27), and non-responders (n = 54). The initial perampanel dose was positively associated with treatment response in patients with RSE or SRSE (OR = 1.27, 95% CI 1.03-1.57, p = 0.025), while the maximum dose was negatively associated with treatment response (OR = 0.74, 95% CI 0.58-0.96, p = 0.022). Hypoxia caused seizures in six patients; five died in hospital and one had severe disability. A statistically non-significant tendency toward better response was found in patients with unique SE type and cause, particularly in nonconvulsive status epilepticus (NCSE) without coma (NCSE without coma vs. generalized tonic-clonic seizure: OR = 4.14, 95% CI 0.98-17.47, p = 0.053). In the high-dose (≥ 16 mg/day) groups, although distributions of modified Rankin Scale (mRS) scores were similar between perampanel responders and non-responders at discharge, a greater proportion of perampanel responders had less change in mRS scores from baseline than did perampanel non-responders (median mRS: 0 vs 4, p = 0.064). No cardiorespiratory adverse events or laboratory abnormalities were noted with perampanel treatment. CONCLUSIONS: Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE.

Aggressive cytoreduction and multiple subpial cortical transections may obtain good surgical outcomes in refractory epilepsy with multiple epileptic foci.

BACKGROUNDS: Epilepsy surgery is the most efficacious therapeutic modality for patients with medical refractory epilepsy, especially resective surgery. However, the variable etiologies and multiple epileptic foci are usually associated with the outcomes. The aim of this study was to demonstrate that combination of different intervention procedures might be an alternative option for patients of refractory epilepsy. METHODS: We retrospectively analyzed pre-operative and post-surgical outcomes in 30 patients who received epilepsy surgery between January 1, 2010 and December 31, 2014 at Chang Gung Memorial Hospital (CGMH), Linkou, according to Engel's classification. RESULTS: Twenty-six of the 30 patients (86.7%) had good outcomes, sum of class I and class II after epilepsy surgery. The good outcome rate of our complicated group was 80.0% (12/15), compared to 93.3% (14/15) in the simple group, but no significant differences between the two groups (p = 0.569). Four patients whose epileptic foci involved eloquent area and received multiple subpial cortical transection, and good outcome rate was 75% (3/4). At last, six patients had previously failed epilepsy surgery and received a reoperation, with a good outcome rate of 83.3% (5/6). CONCLUSION: After complete pre-surgical evaluation and combined interventional procedures, the patients with refractory epilepsy had satisfactory outcomes and few neurological complications. Moreover, re-operation can improve the outcome in some patients who previously failed epilepsy surgery.

Evaluation of the pathophysiology of classical trigeminal neuralgia by blink reflex study and current perception threshold testing.

We recruited 49 patients with classical trigeminal neuralgia (TN) according to the latest guidelines of the International Classification of Headache Disorders, and divided them into an acute (30 days onset; 36 patients) group. We used blink reflex study and current perception threshold (CPT) testing to evaluate the painful facial areas and contralateral non-painful areas of patients with classical TN. CPT 5 Hz examinations, which correlate with unmyelinated fiber function, showed significantly decreased CPTs in the acute stage (11.62 +/- 6.99 vs. 18.69 +/- 9.66, P = 0.025), but significantly increased CPTs in the chronic stage (26.67 +/- 18.65 vs. 19.69 +/- 13.70, P = 0.010) on the painful side when compared with the contralateral non-painful side. However, CPTs at 250 Hz (Adelta) and 2000 Hz (Abeta) examinations did not show significant differences between the painful and non-painful sides. In contrast, only three (3/49) patients showed an abnormal trigeminal nerve stimulation on the ipsilateral painful side by blink reflex study. The findings suggest that classical TN is not a simple large-myelinated nerve fiber dysfunction but a more complex process with a main dysfunction of unmyelinated nerve fibers.