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.

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.

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.

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.

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.

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.

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).

Effectiveness and safety of perampanel in adults with mesial temporal epilepsy: A single-center postmarketing study in Taiwan.

Mesial temporal lobe epilepsy (MTLE) is a common epilepsy syndrome often refractory to antiepileptic drug (AED) treatment. The purpose of this study was to evaluate the effectiveness and tolerability of perampanel (PER) as add-on treatment for patients of MTLE.We pooled retrospective data from adult patients with MTLE, from a tertiary center in Taiwan, who were prescribed PER between March 2016 and December 2016. The retention, responder, and seizure-free rate as well as the treatment emergent adverse events were assessed after 6 months of PER adjunctive treatment in this single-center postmarketing study.Review of medical records revealed that adequate data were available for 44 patients who were being administered PER (mean age: 42.0 ±â€Š13.3 years, 24 females; baseline mean seizure frequency: 5.4 per 28 days). Twelve patients exhibited hippocampal sclerosis (HS). Open-label PER was added to ongoing medications. Twelve patients withdrew because of ineffectiveness (n = 6) or adverse effects (n = 6). The retention rate was 72.7% at 6 months. On final evaluation, with a mean PER dose of 5.7 mg/day for 6 months, a ≥50% reduction in seizure frequency was observed in 46.9% of the patients, and 5 patients became seizure-free. The effectiveness was similar for patients with or without HS. Twenty-three patients (52.3%) experienced adverse effects. The most common adverse effects were dizziness, ataxia, and irritability.Our results suggest that PER, at doses of 2 to 12 mg/day, reduces seizure frequency effectively with acceptable safety profiles for adults with MTLE.

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.

Different routes of heroin intake cause various heroin-induced leukoencephalopathies.

OBJECTIVE: Toxic leukoencephalopathy is a rare but critical neurological disorder in heroin abusers. Our aim is to compare the clinical manifestations, brain MRIs and prognoses of heroin-induced leukoencephalopathy by different intake routes. METHODS: We present two patients with toxic leukoencephalopathy caused by intravenous (IV) injection of heroin and 48 additional cases from systematic reviews of the literature published between 1994 and 2018. RESULTS: Among the 50 heroin abusers who developed leukoencephalopathy, inhalation was the most popular route (60%), followed by IV injection (30%) and snorting (10%). Mental changes, mutism and urine/fecal incontinence were the major symptoms in patients who IV injected heroin, while cerebellar ataxia and dysarthria were more common among those who inhaled heroin. Delayed-onset encephalopathy uniquely occurred in those who IV injected heroin, whereas progressive encephalopathy was more commonly observed in those who inhaled heroin. Clinical improvement was observed in 60% of patients, the overall mortality rate was 12%, and higher mortality was observed in patients who used the inhalation route (16.7%). The hallmarks on the MRIs of those who inhaled heroin were posterior to anterior involvement of the cerebral white matter and lesions in the posterior limbs of the internal capsules, cerebellum and brainstem. In contrast, those who IV injected heroin had more frequent lesions in the subcortical U fibers and the genu of the internal capsules. CONCLUSION: These data could help physicians make an early diagnosis and predict prognosis and suggest that prompt antioxidative or symptomatic treatments might reduce the long-term consequences and mortality of heroin-induced leukoencephalopathy.

Correlation of vocals and lyrics with left temporal musicogenic epilepsy.

Whether the cognitive processing of music and speech relies on shared or distinct neuronal mechanisms remains unclear. Music and language processing in the brain are right and left temporal functions, respectively. We studied patients with musicogenic epilepsy (ME) that was specifically triggered by popular songs to analyze brain hyperexcitability triggered by specific stimuli. The study included two men and one woman (all right-handed, aged 35-55 years). The patients had sound-triggered left temporal ME in response to popular songs with vocals, but not to instrumental, classical, or nonvocal piano solo versions of the same song. Sentimental lyrics, high-pitched singing, specificity/familiarity, and singing in the native language were the most significant triggering factors. We found that recognition of the human voice and analysis of lyrics are important causal factors in left temporal ME and provide observational evidence that sounds with speech structure are predominantly processed in the left temporal lobe. A literature review indicated that language-associated stimuli triggered ME in the left temporal epileptogenic zone at a nearly twofold higher rate compared with the right temporal region. Further research on ME may enhance understanding of the cognitive neuroscience of music.

Clinical correlation and prognostic implication of periodic EEG patterns: A cohort study.

OBJECTIVE: Despite increasing amounts of research on periodic discharges (PDs), large clinical studies regarding their prognostic value are lacking. The aim of the current study was to evaluate the clinical implications and prognostic value of PDs. METHODS: In this single-center retrospective cohort study, we included patients who underwent electroencephalographic recording either during hospitalization or from our outpatient clinics. Demographic data, associated seizure events, use of antiepileptic drugs, and outcomes at discharge were analyzed. Multivariate logistic regression analysis was used to evaluate associations between clinical factors and functional outcomes. RESULTS: Four hundred and twenty patients were enrolled during a 17-year period, with a mean age of 66 years. The main etiologies included systemic infection (24%), anoxia (15%), and ischemic stroke (12%). Recent seizures were identified in 283 patients (67%), of whom 84 (30%) had status epilepticus. One hundred and fifty-four patients (37%) did not survive to hospital discharge. In multivariate analysis, old age (>65years; OR=2.55; 95% CI=1.57-4.16; P<0.001) was the strongest predictor of mortality, followed by systemic infection, anoxic encephalopathy, cefepime encephalopathy, and the occurrence of status epilepticus. Conversely, the use of antiepileptic drugs was negatively associated with mortality (OR=0.50; 95% CI=0.28-0.87; P=0.02). CONCLUSIONS: PDs were associated with high rates of comorbidities and recent seizures, while the use of antiepileptic drugs was associated with a lower rate of mortality.

Preliminary Asian experience of using perampanel in clinical practice.

BACKGROUND: To analyze the efficacy and safety of perampanel over a 3-month period in a sample of Asian people with epilepsy. METHODS: The efficacy and safety of perampanel as an adjunctive therapy for patients with epilepsy were retrospectively reviewed and analyzed. Patients were categorized according to seizure type, concomitant antiepileptic drug usage, and perampanel dosage. RESULTS: A total of 210 patients were included in the study and 131 patients completed 3 months of perampanel treatment. The average dosage of perampanel was 5.31 mg/day, and the 50% responder rate (≥50% seizure frequency reduction) in all patients was 45.8%, with a 27.5% seizure-free rate. For focal seizures, focal to bilateral tonic-clonic seizures, and primary generalized seizures, the 50% responder rates were respectively 29.4%, 49.5%, and 36.4%. In total, 39.5% of patients experienced adverse events within 3 months of observation period, and the rate of drug withdrawal due to adverse events was 8.6%. Dizziness, ataxia, irritability/aggression were the most common adverse events. CONCLUSIONS: The efficacy and safety of perampanel in a real-world setting with Asian patients is comparable to that in clinical trials that have included fewer Asian patients.

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.

Evaluating the impact of hippocampal sparing during whole brain radiotherapy on neurocognitive functions: A preliminary report of a prospective phase II study.

BACKGROUND: Whole brain radiotherapy (WBRT) is the treatment of choice for patients with brain metastases. However, neurocognitive functions (NCFs) decline due to impaired hippocampal neurogenesis might occur thereafter. It is hypothesized that conformal hippocampal avoidance during the course of WBRT (HA-WBRT) might provide meaningful NCF preservation. Our study aims to demonstrate the impact of delivering HA-WBRT on NCF changes in patients receiving WBRT. METHODS: Twenty-five patients who were referred for prophylactic cranial irradiation (PCI) or treating oligometastatic brain disease were enrolled in the study. Before the HA-WBRT course, all participants should receive baseline neurocognitive assessment, including memory, executive functions, and psychomotor speed. The primary endpoint was delayed recall, as determined by the change/decline in verbal memory [Wechsler Memory Scale - 3rd edition (WMS III)- Word List score] from the baseline assessment to 4 months after the start of HA-WBRT. RESULTS: Only three patients belonged to the clinical setting of PCI; the remaining 22 patients had oligometastatic brain disease. Regarding neurocognitive outcomes, no statistically significant differences were found between various NCF scores obtained at baseline and at post-radiotherapy intervals, in immediate verbal memory and non-verbal memory, except for delayed recall memory on Word List (F = 5.727, p = 0.048). CONCLUSIONS: Functional preservation by hippocampal sparing during WBRT could largely be achieved in this study, which also suggests that HA-WBRT should be a feasible technique preserving neurocognitive functions while maintaining intracranial control.

Caspr2 antibody limbic encephalitis is associated with Hashimoto thyroiditis and thymoma.

BACKGROUND: Contactin-associated protein 2 (Caspr2) antibody is a neuronal surface antibody (NSAb) capable of causing disorders involving central and peripheral nervous systems (PNS). Thymoma can be found in patients with Caspr2 antibodies and is most frequently associated with PNS symptoms. Myasthenia gravis can be found in these patients, but Hashimoto thyroiditis (HT) has not been reported. METHODS: A 76-year-old woman presented with sub-acute-onset changes in mental status. Further investigations revealed thymoma and HT. The presence of NSAb was tested by immunofluorescence on human embryonic kidney-293 cells. Treatment included corticosteroids, azathioprine, thyroxine, plasmapheresis, and thymectomy. RESULTS: Caspr2 antibody was positive in serum but absent in CSF. Brain magnetic resonance imaging (MRI) showed diffuse cortical atrophy, but did not change significantly after treatments. Brain positron emission tomography (PET) revealed diffuse hypometabolism over the cerebral cortex. The patient's mental status only partially improved. CONCLUSIONS: In Caspr2 antibody-associated syndromes, thymoma can occur in patients presenting only with LE, and HT can be an accompanying disease. Brain MRI and PET may not show specific lesions in limbic area. Patients with Caspr2 antibodies and thymoma may not have good prognosis.

Epileptic seizures in neurofibromatosis type 1 are related to intracranial tumors but not to neurofibromatosis bright objects.

OBJECTIVE: To investigate the relationship between intracranial lesions and epileptic seizures in neurofibromatosis type 1 (NF1) patients. BACKGROUND: NF1 is one of the most common autosomal dominant neurocutaneous disorders, and epilepsy is more prevalent in NF1 patients than in the general population. Epileptic seizures were found to be related to various types of intracranial lesions in NF1 patients. METHODS: The clinical characteristics of NF1 (1986-2006 in Chung-Gung Memorial Hospital), diagnosed on the basis of the criteria of the National Institutes of Health Consensus Conference (1988), were reviewed by 2 neurologists. We diagnosed epileptic seizures of NF1 patients on the basis of clinical appearances and a history of antiepileptic drugs. Magnetic resonance images were also evaluated by 2 neuroradiologists to confirm the locations of brain tumors or neurofibromatosis bright objects (NBOs). The locations of NBOs were classified into 4 categories: cortex and hippocampus, subcortical white matter, basal ganglia, and infratentorial area. The association between the location of the lesions and the occurrence of seizure in NF1 patients was analyzed statistically. RESULTS: The medical records of 630 NF1 patients were reviewed. In this cohort, 37 (5.87%) NF1 patients had epileptic seizures. The patients include 22 males (59.5%) and 15 females (40.5%). The mean seizure onset age was 14.8 years (2 months to 72 years). The most common seizure pattern was partial onset seizures, 3 simple partial seizures, and 14 complex partial seizures. Other seizure types found include 15 primary generalized seizures (2 absence seizures and 13 generalized tonic-clonic seizures), 2 infantile spasms, and 3 unclassified. A total of 172 (23 with epilepsy and 149 without epilepsy) NF1 patients underwent MRI examinations. NBOs were identified in 16 (69.6%) epilepsy patients and in 108 (72.5%) patients without epilepsy. The location or the number of these intracranial lesions does not show significant correlation with the occurrence of epilepsy in our cohort. Among 11 NF1 patients with intracranial tumors, 4 patients had seizures (36.36%), vs. 19 out of 161 NF1 patients (11.80%) without tumors. CONCLUSION: The occurrence of epileptic seizures in NF1 patients is related to intracranial tumors but not to NBOs.

Long-term video-EEG monitoring for paroxysmal events.

BACKGROUND: Long term video-electroencephalography monitoring (VEM) has been widely used for the diagnosis, classification, and management of seizures. Few studies have systemically examined its safety issues and clinical utility. This prospective study investigates the general clinical application of long term VEM in the management of paroxysmal events. METHODS: This study cohort consisted of patients admitted to the inpatient VEM unit at Chang Gung Memorial Hospital (Lin-Kou). Standard 19 channel scalp electroencephalography (EEG), electrocardiography (ECG), and simultaneous video images were recorded continuously for 2 full days. Patient characteristics, and clinical, video-EEG and safety data were obtained and analyzed. The diagnosis and management of paroxysmal events before VEM were compared with those after VEM. RESULTS: Habitual events were recorded in 54.3% of the 129 patients, and VEM had a yield rate of 76% (events recorded or newly recorded interictal discharges) indetermining the nature of the events. Eleven patients had seizure clusters, but there was no status epilepticus or electrode-related injury. After VEM, the diagnostic categories were changed in 41.1% of the patients, and 40.3% had revisions in management. CONCLUSIONS: Long term VEM is a safe diagnostic tool providing a high diagnostic yield rate and directing adjustment of management for patients with paroxysmal events.

Neurological complications involving the central nervous system in neurofibromatosis type 1.

OBJECTIVE: To investigate the neurological complications and characteristics of intracranial lesions in patients with neurofibromatosis type 1 (NF1) in Taiwan. BACKGROUND: Neurofibromtosis type 1 is a common autosomal dominant disorder characterized by cafe au lait spots, peripheral neurofibromas, Lisch nodules, and axillary freckling. Intracranial lesions such as optic gliomas and neurofibromatosis bright objects (NBOs) are common. METHODS: Patients with the diagnosis of NF1 based on criteria from the National Institutes of Health Consensus Conference (1988) between Jan. 1, 1983 and Oct. 30, 2005 were retrospectively evaluated at the Chung-Gung Memorial Hospital (CGMH). Case histories were analyzed for neurological complications of epilepsy, stroke, and pituitary as well as other intracranial lesions. Magnetic resonance imaging (MRI) examinations were also focused on the number, distribution, and change of NBOs as well as intracranial pathology including optic pathway or brain gliomas. RESULTS: The study population included 69 patients (28 females and 41 males) mean 25.1 +/- 15.0 years. Brain MRIs for 24 patients identified 1 meningioma, 1 optic glioma, and 4 other intracranial gliomas. In total, 14 patients had 52 NBOs. The most common anatomical sites for the NBOs were the globus pallidus and thalamus (15.4%), followed by the cerebellum and subcortical white matter (11.5%). The most commoly identified neurological complications were epilepsy (8.7%) and cerebral infarction (7.2%). These complications, however, were not correlated with intracranial lesions. CONCLUSIONS: Neurofibromatosis bright objects are frequent neuroimaging findings in patients with NF1, and are at high risk of transforming into tumors. The incidences of epilepsy and young-onset cerebral infarction in NF1 patients in this study are higher than those in the general population. Neuroimaging studies are thus essential for NF1 patients to determine the extent of neurological complications; although the imaging findings may not be completely correlated with the clinical manifestations.