Fumikazu Sano

Valproate sodium enhances body weight gain in patients with childhood epilepsy: A pathogenic mechanisms and open-label clinical trial of behavior therapy

OBJECTIVES Excessive weight gain associated with valproate sodium (VPA) may predispose patients with epilepsy to other health problems such as insulin resistance. The purpose of this study was to examine the changes in body weight and several biochemical parameters in children receiving VPA treatment. The effects of behavior therapy for epileptic children with VPA-induced weight gain are discussed. METHODS Fifteen patients newly diagnosed with epilepsy were included in the study. The following parameters were measured: body weight, body mass index (BMI), serum glucose, serum insulin, serum VPA concentration and serum free carnitine. In addition, behavior therapy was introduced at the initiation of VPA therapy, and lasted at least for 2 years. RESULTS After 6 months of follow-up, there were eight (53%) patients in whom weight gain was demonstrated. Significant increases in the serum insulin level and the insulin/glucose ratio were observed in the weight gain group (p<0.01). All patients with significant weight gain showed increased appetite. However, BMI stopped increasing with intensive behavior therapy. CONCLUSIONS These findings suggest that an increase in serum insulin and insulin/glucose levels may cause weight gain, possibly by stimulating appetite, and that weight changes seem to be reversible with intensive behavior therapy without discontinuation of VPA.

EEG improvements with antiepileptic drug treatment can show a high correlation with behavioral recovery in children with ADHD

We investigated the relationship between neuropsychological disturbance, assessed using the global assessment of functioning (GAF) and the ADHD-rating scale (ADHD-RS), paroxysmal EEG abnormalities, and treatment with valproate sodium (VPA) in children with both attention deficit hyperactivity disorder (ADHD) and paroxysmal abnormality (PA). Participants with ADHD but without obvious epilepsy were recruited between April 1, 2003 and March 31, 2008. Paroxysmal abnormality was scored by measuring the spike frequency. Of 46 children, 16 showed PA; 3 of the 16 were excluded because no follow-up EEG was available. The EEG improved with VPA treatment in 5 of 8 patients with frontal PA and 3 of 5 patients with rolandic PA. While 83.3% of the patients with improvements in both assessments had frontal PA, only 16.7% had rolandic PA. The patients with frontal PA showed a significantly higher correlation between PA frequency and improvement in ADHD-RS compared with those with rolandic PA. In this study of children with ADHD, EEG improvement with antiepileptic drug treatment showed a high correlation with behavioral improvements as shown by ADHD-RS and GAF scores. However, this was not a population-based study, and the relative importance of detecting and treating PA in ADHD has yet to be determined.

Repeated seizures induce prefrontal growth disturbance in frontal lobe epilepsy

BACKGROUND The possible consequences of seizures in the immature brain have been the subject of much conjecture. We prospectively measured frontal and prefrontal lobe volumes using three-dimensional (3D) magnetic resonance imaging (MRI)-based volumetry in patients with frontal lobe epilepsy (FLE) presenting with the same seizure semiology. The pathogenesis of repeated seizure-induced brain damage is discussed herein. METHODS Serial changes in regional cerebral volumes were measured in two patients with FLE presenting with intractable clinical courses and cognitive impairments/behavioral problems (FLE(+)) and four FLE patients without cognitive impairments/behavioral problems (FLE(-)). Eleven normal subjects (4-13 years old) served as controls. Volumes of the frontal and prefrontal lobes were determined using a workstation, and the prefrontal-to-frontal lobe volume ratio was calculated. RESULTS Frontal and prefrontal lobe volumes revealed growth disturbance in FLE(+) compared with those of FLE(-) and control subjects. In addition, prefrontal-to-frontal lobe volume ratio increased serially in FLE(-) similarly to controls, but was stagnant or decreased in FLE(+). Prefrontal growth also revealed more rapid recovery in a FLE(+) patient with shorter active seizure period. CONCLUSION These findings suggest that repeated seizures may lead to prefrontal growth disturbance. The occurrence of frequent seizures in patients with FLE may be associated with prefrontal lobe growth retardation, which relates to neuropsychological problems and ultimate neuropsychological outcome.

Efficacy and safety of add-on levetiracetam in refractory childhood epilepsy

PURPOSE The purpose of the present study was to evaluate the efficacy and safety of levetiracetam (LEV) in refractory epileptic children. METHODS The study group included 61 outpatients (7 generalized, 48 localization-related, 3 undetermined, 3 unclassified) aged between 16 months and 18 years. LEV was given twice daily at a total dose of 10 mg/kg/day. The final mean dose was 50.7 mg/kg/day. The mean number of prior anti-epileptic drugs was 5.2. The entire treatment period was more than 6 months after LEV administration. RESULTS Fifteen children (24.6%) became seizure-free for 6 months after starting LEV, and 18 (29.5%) had a seizure reduction of more than 50% for the entire 6 months. The response rate was 33/61 (54.1%). Responders included 2/3 of patients (66.7%) with epilepsy with continuous spikes and waves during slow sleep and 13/19 (68.4%) with frontal lobe epilepsy. The effective dosage of LEV in the responders demonstrated a wide range (mean, 46.1 mg/kg/day; range, 19.4-59.1 mg/kg/day), and showed bimodal distribution. Adverse events occurred in only two patients who did not require LEV discontinuation. CONCLUSION LEV represents an important addition to the treatments available for refractory epileptic children.

Do sequential EEG changes predict atypical clinical features in rolandic epilepsy

Aim  Although the prognosis for rolandic epilepsy is regarded to be favourable, a small proportion of cases that initially present as rolandic epilepsy evolve into atypical benign partial epilepsy (ABPE) of childhood. The purpose of our study was to determine electroencephalogram (EEG) criteria in relation to atypical seizure manifestations, and cognitive and behavioural problems in rolandic epilepsy.

Developmental changes in frontal lobe function during a verbal fluency task: A multi-channel near-infrared spectroscopy study

OBJECTIVE Near-infrared spectroscopy (NIRS) is commonly used to investigate continuous changes of brain activation and has excellent time resolution. Verbal fluency task (VFT) is widely used as a neuropsychological test of frontal lobe function. The aim of this study was to investigate normal developmental change in frontal lobe function during VFT performance using multi-channel NIRS, specifically focusing on oxygenation hemoglobin (oxyHb) changes. METHODS The subjects were 9 adults and 37 childrens who were all healthy right-handed volunteers. Children were divided into four age groups (group A, 6-8 years; group B, 9-11 years; group C, 12-14 years; group D, 15-18 years). The [oxyHb] changes were measured with 22 channels of NIRS during VFT. We defined the frontopolar region as the region of interest for analysis, and calculated the Z-score to compare the data between groups. RESULTS The task performance changed with age. There were significant differences between group A and other groups. The Z-score of [oxyHb] also significantly increased with age, when comparing adults to groups A and B. The task performances decreased with time in all groups. In contrast, [oxyHb] only continued to increase in the adult group. CONCLUSION The verbal retrieval functions begin to mature in early adolescence and continue to grow up to adulthood.

Effects of levetiracetam on seizure frequency and neuropsychological impairments in children with refractory epilepsy with secondary bilateral synchrony

PURPOSE In epilepsy with continuous spikes and waves during slow sleep (CSWS), which is a representative epileptic syndrome of secondary bilateral synchrony (SBS), the urgent suppression of this electroencephalographic (EEG) abnormality may be necessary to prevent the progression of neuropsychological impairments. The purpose of this study was to determine the efficacy of levetiracetam (LEV) on SBS, seizure frequency, and neuropsychological impairments in children with refractory epilepsy. METHODS Eleven (seven male and four female) patients with refractory epilepsy with SBS on EEG, aged between 4.7 years and 11.3 years, were included in this study. After a 3-month baseline period, the patients were given LEV at an initial dose of 10mg/kg/day for the first week, followed at increments of 5mg/kg/day every week, up to 20mg/kg/day. The LEV dose was then adjusted up to a maximum of 60mg/kg/day, according to the clinicians judgment. EEG recordings and clinical evaluations were performed every 3 months, focusing on SBS. The occurrence of SBS was then scored, and the relationship between the score and the response to LEV treatment was evaluated. In comparison with the baseline SBS frequency, the EEG response to LEV treatment was classified, and responders were identified as having a ≥50% reduction in SBS frequency. In addition, in comparison with the baseline seizure frequency, response to LEV treatment was classified. Responders were identified as patients with complete cessation (100% seizure control) and a response of ≥50% reduction in seizures. Furthermore, neuropsychological impairments such as hyperactivity, impulsiveness, and inattention were evaluated before and after LEV treatment. RESULTS Eight patients (72.7%) were considered responders. In addition, all eight patients were also considered responders for clinical seizures. Furthermore, 7 of 8 (87.5%) patients with response showed decreased hyperactivity and impulsivity after LEV administration. CONCLUSIONS The present data clearly indicate the usefulness of LEV in reducing both SBS on EEG and seizure frequency. LEV represents an important addition to the treatments available for refractory childhood epilepsies with SBS on EEG.

Characteristics of headache in children with epilepsy

PURPOSE The association of headache with seizures is well known to neurologists but poorly understood. The purpose of this prospective study was to evaluate the types and frequency of seizure-associated headaches among pediatric patients with epilepsy, and to identify their risk factors with special attention to the anatomic localization of the epileptogenic focus and seizure classification. METHODS Patients with focal and generalized active seizures and on treatment at the time of questionnaire administration were included. Patients were prospectively interviewed by questionnaire as to whether or not they suffered from headaches associated with epileptic seizures. RESULTS Of 98 patients (age range: 5-18 years), 34 (34.7%) complained of seizure-associated headaches. In patients with seizure-associated headaches, headache was significantly more frequent (31/74, 41.9%) with partial seizures than with generalized seizures (3/24, 12.5%; p=0.012). The frequency of seizure attacks was 4.1 times per year in patients with seizure-associated headache and 1.3 times per year in those with non-seizure-associated headache. Of the 34 patients, 20 (58.8%) complained of headache at the frontal region. CONCLUSIONS The location of headache was not always in agreement with electroencephalographic focus. Headache was more frequent in patients with partial epilepsy and frequent seizures.

Risk factors for seizure recurrence in children after first unprovoked seizure

The question of whether to treat a patient after a first unprovoked seizure is controversial. This prospective study assessed the time to recurrence and risk factors for seizure recurrence after a first unprovoked seizure in children.

Parental thoughts and actions regarding their child's first febrile seizure

Little is known about what parents think and how they act when their child experiences febrile seizure (FS). This study therefore surveyed parents of 78 children who had experienced a first FS regarding their thoughts and actions.