Risk factors of hyperammonemia in epilepsy patients with valproic acid therapy.

BACKGROUND: Hyperammonemia can occur after acute overdose or chronic use of valproic acid (VPA). Although VPA-related hyperammonemic encephalopathy (VHE) is a rare complication of VPA therapy, early recognition of VHE and identifying its risk factors are important because VHE can lead to loss of consciousness and increased seizure frequency. PURPOSE: The purpose of our study is to evaluate the risk factors of hyperammonemia in epilepsy patients during treatment with VPA therapy. METHODS: We reviewed the medical records of 1084 adult patients with epilepsy and enrolled 116 patients with VPA therapy who had results of blood levels of ammonia over a 3-year period. Hyperammonemia was defined as a blood ammonia level exceeding 80 µg/dL. Correlations of blood levels of ammonia with dosages and blood levels of VPA were evaluated. We further performed univariate and multivariate linear regression analyses to identify risk factors for hyperammonemia in epilepsy patients treated with VPA therapy. RESULTS: Blood levels of ammonia were well correlated with dosages of VPA (p = 0.036), but not with blood levels of VPA (p = 0.463). Hyperammonemia was more common in patients with higher VPA dosage and higher total drug loads of concurrent antiseizure medications (ASMs). Hyperammonemia was also associated with the use of topiramate and phenobarbital. In multivariate analysis, we identified total drug load of ASMs (p = 0.003) and use of topiramate (p = 0.007) as independent predictors of hyperammonemia. Four patients (4/116, 3.4 %) had clinical symptoms of VHE. Three of them had hyperammonemia while the other patient had normal blood level of ammonia with a high blood level of VPA. CONCLUSION: Our study shows that higher total drug loads of concurrent ASMs and use of topiramate were independent risk factors of hyperammonemia in epilepsy patients with VPA therapy. Although the incidence of VHE was not high in our study, clinicians should be aware of this potential adverse effect of VPA therapy, especially in patients with polytherapy of ASMs including topiramate.

Potential efficacy and safety of eslicarbazepine acetate oral loading in patients with epilepsy.

Eslicarbazepine acetate (ESL) is a new antiseizure medication (ASM) approved as an adjunctive therapy or monotherapy for focal onset seizures. We performed this study to explore the potential efficacy and safety of ESL oral loading in selected patients with epilepsy. Thirty adult patients with status epilepticus or acute repetitive seizures were enrolled, and ESL was administered at a single loading dosage of 30 mg/kg. Plasma levels of an active metabolite of ESL, monohydroxy derivative (MHD), were measured at 2, 4, 6, 12, and 24 h after ESL oral loading. Two thirds of the patients reached a therapeutic level of MHD 2 h after ESL loading, and most of the patients achieved a therapeutic range within 12 h after loading. Plasma MHD levels did not rise above the supratherapeutic level in any patient throughout the study. The reported adverse effects included one patient with gaze-evoked nystagmus and another patient with a rash. No serious adverse events leading to drug discontinuation occurred. There was no discernible difference in sodium levels before and after ESL oral loading. Our study findings suggest that ESL oral loading could be a useful therapeutic option for patients with epilepsy who need rapid elevations in the therapeutic levels of ASMs.

Headache Is a Common Aura in Patients with Generalized Seizures.

Background and Purpose: Although aura in epilepsy is usually considered as a phenomenon in patients with focal seizures, headache can occur as an aura or solitary epileptic symptom in patients with generalized seizures. Methods: We performed a 14-year retrospective study of patients with generalized seizures and analyzed the proportion and characteristics of patients with auras including headache. Results: Among the 102 patients diagnosed with generalized seizures, aura was reported in 45 patients and headache was the most common aura in 26 patients. The age of onset of seizures was significantly lower in patients with headache as an aura than in patients without headache (14.8±3.8 vs. 24.7±16.2; p=0.003). Conclusions: Our study showed that headache was the most common aura in patients with generalized seizures and patients with a younger age of onset of seizures were more likely to experience headache as an aura in these patients.

Treatment outcome following the transition to adult epilepsy care in childhood-onset epilepsy.

INTRODUCTION: Transition from pediatric to adult epilepsy care in patients with childhood-onset epilepsy can be challenging, and several aspects should be considered, including comorbidities, achieving social milestones, and adjustment of anti-seizure medications (ASMs). However, there is limited information regarding the treatment outcome following the transition to adult epilepsy care in childhood-onset epilepsy. MATERIALS AND METHODS: We performed a 13-year retrospective study of patients with childhood-onset epilepsy who had been transferred to our adult epilepsy clinic. Treatment outcomes were divided into two groups: seizure improvement (at least 50% reduction of seizure) and stationary or worsening seizures. RESULTS: Among the 2,365 patients in our epilepsy cohort, 140 with childhood-onset epilepsy were transferred to adult epilepsy care. Forty-nine patients (35.0%) experienced improvement of seizures, whereas 91 patients (65.0%) reported stationary or worsening seizures following transition. Patients in the improvement group were younger at the time of transition than patients in the stationary or worsening group (p = 0.004) and had a lower number of ASMs before the adjustment (p = 0.001). Interestingly, patients in the improvement group had a greater chance of epileptiform discharges on EEG than patients in the stationary or worsening group (38/49 vs 54/91, p = 0.03). CONCLUSION: Our study shows that one-third of patients having childhood-onset epilepsy can experience seizure improvement following transition to adult epilepsy care, and the presence of epileptiform discharges on EEG may not necessarily mean a poor prognosis or drug-resistant epilepsy following the transition.

The Increased Interleukin-6 Levels Can Be an Early Diagnostic Marker for New-Onset Refractory Status Epilepticus.

New-onset refractory status epilepticus (NORSE) is a condition defined as the occurrence of refractory status epilepticus in patients without active epilepsy and no other acute causes of seizure. Although there is evidence that immune-mediated pathogenesis has a pivotal role in the epileptogenesis of NORSE, the diagnosis of NORSE is usually made on the clinical observation because there is no established biological marker suggesting the diagnosis of NORSE. We recently encountered a NORSE patient who was successfully treated with immunotherapy including tocilizumab, an anti-interleukin-6 (IL-6) receptor monoclonal antibody, and the markedly increased levels of serum and cerebrospinal fluid IL-6 were the only laboratory abnormality during the early treatment of the patient.