HFA analysis using scalp electroencephalograms in two cases of Rasmussen's syndrome.

OBJECTIVE: In recent years, wide-band EEGs have been used to assess brain activity, and their effectiveness in the pathological analysis of epilepsy has been demonstrated. This report describes two cases of Rasmussen's syndrome (RS) in which high-frequency scalp EEGs were retrospectively analyzed to assess the pathological condition of epilepsy in RS. METHODS: The two RS cases were divided into three periods: incipient, stable, and frequent seizure periods. Using the EEG record of each period, interictal epileptiform discharges (IEDs) were visually extracted. Subsequently, a time-frequency analysis was performed to calculate the rate of high-frequency activities (HFAs) (IED-HFA rate). Finally, differences between the three periods were examined. RESULTS: IED-HFA rates significantly increased in the frequent seizure period compared with the stable period in both cases(P < 0.05). CONCLUSION: there was a significant increase in HFAs superimposed over IEDs during the frequent seizure period compared to the stable period. HFAs are thought to be associated with epileptogenicity. Similarly, HFAs could be a useful biomarker for the pathological condition of epilepsy in RS.

Clinical impact of the dose and blood concentration of lacosamide in Japanese pediatric patients with epilepsy: A cohort study.

PURPOSE: The relationship between treatment efficacy/tolerability and the dose/blood concentration of lacosamide (LCM) was investigated in a clinical cohort of Japanese pediatric patients with epilepsy. METHODS: This retrospective analysis reviewed the medical records of patients treated with LCM for >6 months at the Department of Pediatrics, Hiroshima University Hospital, from September 2017 to January 2021. The collected data included age, sex, epilepsy type, seizure type, seizure frequency before and after treatment initiation, adverse events leading to LCM discontinuation, dose at any evaluation point, serum concentration, and concomitant antiepileptic drugs (AEDs). RESULTS: The study included 51 patients (31 male patients) between the ages of 2 and 19 years. All patients were Japanese. Epilepsy was classified as focal in 44 patients, generalized in six patients, and combined generalized and focal in one patient. The 50% responder rate for LCM treatment was 56.9%. Seven patients experienced complete seizure control (absence of seizures for 6 months before the follow-up visit). A relationship between dose and blood concentration was identified. Although the blood LCM concentration was higher in the responders than in the nonresponders (7.86 vs. 6.16 µg/mL; p = 0.028), there was no significant difference in dose between the two groups. Lacosamide showed efficacy at a dose >5 mg/kg/day in more than half of the 50% responders. The treatment-emergent adverse events (TEAEs) included seizure aggravation in five patients, irritability in two patients, and somnolence and drug eruption in one patient each. In six patients with TEAEs, the TEAEs developed within 1 month after treatment initiation and led to LCM discontinuation. CONCLUSION: In Japanese pediatric patients with epilepsy, LCM treatment is effective, particularly at higher doses. The blood concentration may be related more to efficacy than to dose. Lacosamide is generally well-tolerated by pediatric patients, and should be used at the maximum tolerable dose (needed to be gradually increased) in patients with otherwise insufficient seizure control. As TEAEs leading to discontinue treatment likely occur in early phase, it is needed to monitor patients carefully if TEAEs would happen in that phase.

Effects of perampanel add-on therapy on immunoglobulin levels in pediatric patients with epilepsy.

BACKGROUND: Perampanel (PER) has a unique pharmacological mechanism and marked efficacy in both focal and generalized epilepsy, but may cause adverse events similar to those of other antiepileptic drugs (AEDs). AEDs can affect multiple organ systems, as well as thyroid function, lipid profiles, and immunoglobulin levels; the low free T4 levels, hyperlipidemia, and low immunoglobulin levels can be caused by AEDs. While many studies have examined conventional AEDs, little is known about the long-term effects of PER on blood parameters. METHODS: We retrospectively reviewed the medical records of 18 pediatric patients with epilepsy who were treated with PER added to >1 other AED. Blood parameters (e.g., blood cell counts, biochemical and thyroid function, and immunoglobulin levels) were investigated at baseline and at 6 and 12 months after initiation of PER. RESULTS: PER did not affect the blood counts, transaminase levels, lipid profile, or thyroid function at 12 months after initiation of PER. However, IgA levels significantly increased (p = 0.00319) without symptoms. IgM levels increased temporarily, but had returned to baseline by 12 months after initiation of PER. CONCLUSIONS: IgA levels were elevated at 12 months after initiation of PER in pediatric patients with intractable epilepsy, although no symptoms were observed. PER did not affect other parameters, including lipid profile and thyroid function.

Successful treatment of intractable life-threatening seizures with perampanel in the first case of early myoclonic encephalopathy with a novel de novo SCN1A mutation.

PURPOSE: Early myoclonic encephalopathy (EME) is a form of developmental and epileptic encephalopathy with myoclonic seizures and a suppression burst on electroencephalogram, which occurs during the neonatal or early infantile period and is characterized by highly intractable seizures and severe development impairment. Although multiple genetic aetiologies of EME have been identified, no SCN1A mutation has been reported. METHODS: We described a female patient with EME due to an SCN1A mutation. RESULTS: She developed frequent myoclonic and apnoeic seizures during the neonatal period. As her seizures were refractory to many antiepileptic drugs, she underwent a tracheotomy and has since been treated with continuous mechanical ventilation. Eventually, perampanel was added, which resulted in the cessation of the apnoeic seizures. Genetic analysis revealed a heterozygous de novo missense mutation in the SCN1A gene (c.2588 T > C:p.Leu863Ser). CONCLUSION: This is the first patient with EME due to anSCN1A mutation to be successfully treated with perampanel. Recently, perampanel was reported to be effective in treating Dravet syndrome, including cases with an SCN1A mutation. Perampanel may contribute to seizure reduction in patients with intractable epilepsy carrying the SCN1A mutation.

High Incidence of Renal Stones in Severely Disabled Children with Epilepsy Treated with Topiramate.

PURPOSE: This study was aimed to assess the accurate incidence of renal stones in severely disabled children treated with topiramate (TPM). METHOD: We reviewed the medical records of severely disabled children with epilepsy under 15 years old who underwent radiological examinations to investigate urinary stones. The study enrolled 26 patients who were divided into two groups. One group had been treated with TPM for at least 1 year and the other had not been treated with TPM, zonisamide, acetazolamide, or other diuretic drugs. We collected parameters from the medical records and compared the groups. RESULTS: All participants were evaluated radiologically, with computed tomography (CT) in two patients, ultrasonography in 22 patients, and both in two. No patient had any morphological abnormality of the kidneys and history of urinary tract infection. There were no significant differences in sex, age, body weight, or feeding manner between the groups, while the incidence of renal stones or calcifications was significantly higher in the TPM-treated group (60 vs. 0%; p = 0.00241). CONCLUSION: There is a high incidence of renal stone formation in severely disabled children treated with TPM.

Clinical profiles associated with serum perampanel concentrations in children with refractory epilepsy.

BACKGROUND: Perampanel (PER) is a new antiepileptic drug (AED) with a novel mechanism of action. Investigations of the efficacy and safety of PER in pediatric and adult patients have increased recently. Although the clinical usefulness and pharmacokinetics of PER have been investigated in adolescent and adult populations, similar studies have not been performed in children. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients treated with PER for more than 6 months in the Department of Pediatrics, Hiroshima University Hospital, between September 2016 and November 2018. We obtained demographic and clinical data including age, sex, epilepsy type, seizure type, seizure frequency before and after treatment initiation, adverse events, reasons for discontinuing PER treatment, doses at evaluation points, serum concentrations, concomitant AEDs, intellectual status, and epilepsy etiology. Seizure types and epilepsy syndromes were classified according to the criteria of the International League Against Epilepsy. RESULTS: The study included 44 patients (22 males) between the ages of 6 months and 16 years. Of those, 10 patients discontinued PER therapy. The 50% response rate was 52.3% in patients treated with PER, and four patients achieved complete seizure control. Perampanel was highly effective in patients with generalized and focal epilepsy (50% responder rates, 52.9% and 50.0%, respectively). Favorable response rates were observed for tonic-clonic, focal nonmotor, and absence seizures with 50% response rates of 54.5%, 50.0%, and 66.7%, respectively. The 50% responder rate was 31.3 for epileptic spasms (ES). Treatment-emergent adverse events (TEAEs) included somnolence (n = 8), irritability (n = 2), ataxia (n = 2), and one case each of dizziness, compulsiveness, and enuresis. Serum concentrations of PER were compared in patients taking concomitant enzyme-inducing antiepileptic drugs (EIAEDs; carbamazepine, phenytoin, and phenobarbital) and those taking concomitant non-EIAEDs. Serum PER concentrations were correlated with dose per body weight in both groups (EIAED: r = 0.765, p = 0.00000212; non-EIAED: r = 0.71, p = 0.0000158). The mean concentration-to-dose (CD) ratio was 2398.4 ng mL-1 mg-1 kg-1 (range: 800-4524.7) in the non-EIAED group and 693.7 ng mL-1 mg-1 kg-1 (range: 344-1309.7) in the EIAED group. Serum PER levels were lower in the EIAED group than in the non-EIAED group. All patients with serum PER concentrations above 400 ng/mL experienced somnolence. CONCLUSIONS: Perampanel is effective against various types of seizures, including ES, in pediatric patients with refractory epilepsy. Furthermore, PER has good tolerability when the dose is adjusted based on serum concentrations. The PER CD ratio was lower in pediatric patients than in adolescents and adults; therefore, clinicians must consider the CD ratio when treating children with PER.

Anti-MOG antibody encephalitis mimicking neurological deterioration in a case of Rett syndrome with MECP2 mutation.

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, resulting in developmental regression after normal development during infancy. Transient presentation of many autistic features is also commonly seen in RTT. Anti-myelin oligodendrocyte glycoprotein (MOG)-antibody encephalitis is an acquired relapsing demyelinating syndrome characterized by a variety of neuroinflammatory symptoms. Here, we report a case of anti-MOG antibody encephalitis in a patient with genetically confirmed RTT, which mimicked many of the features of RTT. CASE REPORT: A three-year-old girl presented with subacute verbal and motor dysfunction, along with involuntary movements and marked irritability. Magnetic resonance imaging (MRI) revealed extensive white matter lesions, with anti-MOG antibodies detected in the serum and cerebrospinal fluid, resulting in an initial diagnosis of anti-MOG antibody encephalitis. However, additional testing of the MECP2 gene was performed in response to persistent involuntary hand movements in combination with progressive verbal and motor deterioration. Sequencing analysis revealed a known pathogenic mutation in MEPC2, indicating a concurrent diagnosis of RTT. CONCLUSION: Both RTT and anti-MOG antibody encephalitis are rare conditions. Similarities in disease presentation suggest that anti-MOG antibody encephalitis may mimic many of the symptoms of RTT.

Recurrence of Epileptic Spasms as Reflex Seizures Induced by Eating: A Case Report and Literature Review.

Background Eating epilepsy (EE) is a rare form of reflex epilepsy in which seizures are induced by eating. It is known that most patients with eating seizures, in fact, suffer from symptomatic temporal lobe epilepsy (TLE), whereas only a few patients with epileptic spasms induced by eating (E-ES) have been reported. Patient Description The patient was an 8-year-old girl whose magnetic resonance imaging (MRI) of the head detected dysgenesis of the corpus callosum, cerebellar hypogenesis, marked cerebral asymmetry, broad polymicrogyria, periventricular heterotopia, and closed lip-type schizencephaly. She experienced E-ES as the second form of recurrent seizures after the first recurrence of spontaneous ES. After E-ES occurred, the EEG findings in the right hemisphere, predominantly over the right centrotemporal region, were clearly exacerbated, although the interictal EEG originally showed left-side-dominant asymmetric hypsarrhythmia. The ictal EEG of the E-ES showed diffuse large triphasic (negative-positive-negative) potentials, predominantly over the right centrotemporoparietal region. Conclusions This is a unique case because the E-ES were recurrent ES, although the previous ES were spontaneous, which may provide insight into the mechanism of E-ES.