Tetsuo Ohyama

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.

Sequential prefrontal lobe volume changes and cognitive dysfunctions in children with Panayiotopoulos syndrome presenting with status epilepticus

Panayiotopoulos syndrome (PS) is usually not associated with neurodevelopmental problems. However, neuropsychological impairments may also be present in at least some of the patients with PS. On the other hand, several degrees of neuronal damage due to status epilepticus (SE) may occur in the cortex. We prospectively measured frontal and prefrontal lobe volumes using three-dimensional magnetic resonance imaging (3D-MRI)-based volumetry in patients with PS with and without SE. Moreover, the neuropsychological outcome in relation to the presence of SE in children with PS is also discussed. We studied six patients with a final diagnosis of PS, including three cases with SE and cognitive impairments/behavioral problems (SE group) and three cases without SE (non-SE group). Serial 3D-MRI studies were performed five times (at onset of clinical symptoms and 1-4 years after onset) in both the SE and non-SE patients. All patients were studied with a set of Wechsler Intelligence Scale for Children, version III (WISC-III) or Wechsler Preschool and Primary Scale of Intelligence tests and the Kaufman Assessment Battery for Children (K-ABC). Growth of the frontal and prefrontal lobes was slightly decreased for some time after SE episodes in the SE patients. Moreover, the prefrontal-to-frontal lobe volume ratio was stagnant for some time after SE in the SE patients. The scores on the neuropsychological tests were decreased in the SE patients. Moreover, the average WISC and K-ABC scores in the SE group remained low and did not reach the levels of the initial examinations. Occurrence of SE in patients with PS at least in some patients may be associated with retarded prefrontal lobe growth, which was related to neuropsychological problems and ultimately, neuropsychological outcomes. Treatment management may be required to prevent SE as much as possible to achieve optimal prognosis in PS at least in some patients.

Effect of levetiracetam on behavioral problems in pervasive developmental disorder children with epilepsy

AIMS We investigated the relationship between behavioral problems, location of electroencephalogram (EEG) paroxysmal abnormalities (PA), and treatment with levetiracetam in children with pervasive developmental disorder (PDD) and epilepsy. METHODS Twelve PDD children with epilepsy were included in the study. All patients had EEG PA (frontal spikes, 8; rolandic, 3; generalized, 1). After a 3-month baseline period, patients were given levetiracetam with an initial dose of 10 mg/kg/day for the first week, followed by increments of 5 mg/kg/day every week. Levetiracetam dosage was then adjusted up to a maximum of 60 mg/kg/day. EEG recordings were performed every 3 months, focusing on PA frequency. We counted the frequency of seizures and EEG PA, and scored instances of panic/aggressive behaviors. RESULTS Eight (66.7%) of the 12 patients were considered to be responders to clinical seizures and EEG findings (≥50% reduction in both seizures and PA frequency). Six (75%) of these eight patients were considered to be responders for behavioral problems (≥50% reduction in panic/aggressive behavior). These six patients had frontal EEG paroxysms, whereas the remaining two patients without behavioral responses had rolandic EEG paroxysms. Patients with frontal PA showed a significantly higher correlation between EEG/clinical seizures and behavioral improvements (p < 0.05). CONCLUSION The present data indicated the usefulness of LEV in reducing behavioral problems related to the reduction of seizures and frontal spikes in PDD for some but not all of the patients. Thus, levetiracetam represents an important addition to treatment for PDD children with epilepsy presenting with frontal EEG paroxysms.

EEG characteristics predict subsequent epilepsy in children with their first unprovoked seizure

One of the most important risk factors for seizure recurrence is the electroencephalogram (EEG) characteristics of children with a first unprovoked seizure. However, the nature of the relationship between the risk factors for subsequent epilepsy and EEG characteristics, especially the localization of EEG paroxysmal abnormalities (PAs), remains unclear. The importance of EEG characteristics, especially the localizations of PAs, as predictors for subsequent epilepsy in children with a first unprovoked seizure was investigated. The participants were recruited from University of Yamanashi Hospital between July 1, 1997 and June 30, 2010 and followed until December 31, 2014. Eligible candidates were children between 1 month and 15 years old who presented with their first unprovoked non-febrile seizure. Awake and sleep EEGs were performed on a 12- or 16-channel machine 7-20 days after a first unprovoked seizure. Agreement regarding the presence of a PA was required for inclusion of the patient in the study. EEG PAs were classified based on the presence of spikes, sharp waves, or spike-wave complexes, whether focal or generalized, that were considered abnormal for age and state. All subjects were followed for more than 4 years. Of 87 subjects, 48 (55.2%) experienced recurrence. On the other hand, of 87 subjects, 52 (59.8%) showed an EEG PA. Of 18 patients with paroxysms in the frontal region, 17 (94.4%) developed epilepsy. Patients with frontal EEG paroxysms had a significantly higher risk of developing epilepsy than those with focal paroxysms in other regions of EEG foci (p<0.05). Moreover, compared with generalized EEG foci, the odds ratios for patients with frontal, RD, occipital, and mid-temporal EEG foci were 85.0 (95% CI: 4.5-1617.1), 9.3 (0.9-96.0), 2.5 (0.1-62.6), and 7.5 (0.5-122.7), respectively. Children with a first unprovoked seizure presenting with frontal paroxysmal EEG abnormalities may be at risk for the development of epilepsy later in life.

Sequential EEG characteristics may predict seizure recurrence in rolandic epilepsy

PURPOSE The prognosis of rolandic epilepsy (RE) is considered favorable. Since a moderate proportion of cases presents with isolated seizures, continuous treatment should be considered only for frequent seizures. Clinical and electroencephalogram (EEG) markers to predict seizure recurrence need to be identified. The purpose of this study was to identify EEG criteria related to seizure recurrence in RE. METHODS There were 10 children (aged 3-10 years; 6 males, 4 females) in the recurrence group and 12 (aged 4-7 years; 6 males, 6 females) in the isolated group. Occurrences of the number of spikes were scored, and the presence of rolandic discharges (RD) in the awake record was evaluated. All patients were evaluated longitudinally, clinically and by EEG, with repeated EEG recordings every 3 months. Clinical and EEG follow-up was performed for ≥4 years. RESULTS Seizure recurrence and extended periods of high-frequency paroxysmal EEG abnormalities (>6 months after onset) were significantly correlated (p<0.001). Moreover, the appearance of RD in awake recordings tended to be more prevalent in the recurrence group than in the isolated group (odds ratio 4.714). CONCLUSION In addition to RD in the awake record, a combination of spike rate and extended periods of high-frequency paroxysmal EEG abnormalities may predict seizure recurrence in RE.

Correlation between perceived stigma and EEG paroxysmal abnormality in childhood epilepsy.

AIMS We investigated the relationship between abnormal electroencephalogram (EEG) findings such as localized EEG paroxysmal abnormality (PA) and the perception of stigma to determine EEG factors associated with perceived stigma in childhood epilepsy. METHODS Participants comprised 40 patients (21 boys, 19 girls; mean age, 14.6 years) with epilepsy at enrollment. The criteria for inclusion were as follows: 1) age of 12-18 years, inclusive; 2) ≥6 months after epilepsy onset; 3) the ability to read and speak Japanese; and 4) the presence of EEG PA. Fifteen healthy seizure-free children were included as a control group. Participants were asked to rate how often they felt or acted in the ways described in the items of the Child Stigma Scale using a 5-point scale. Electroencephalogram paroxysms were classified based on the presence of spikes, sharp waves, or spike-wave complexes, whether focal or generalized. RESULTS Participants showed significantly higher stigma scores than healthy subjects (p<0.01). A higher score reflects a greater perception of stigma. The average total scores of patients presenting with EEG PA at generalized, frontal, RD, midtemporal, and occipital regions were 2.3, 4.0, 2.4, 3.2, and 2.2, respectively. The scores of all questions were higher in the frontal group than those in other regions (p<0.01). Children presenting with frontal EEG PA perceived a greater stigma than children presenting with nonfrontal EEG PA (p<0.01). CONCLUSION A relationship was identified between frontal EEG PA and a greater perception of stigma. Further studies are needed to confirm whether frontal EEG PA may function as a mediator of emotional responses such as perceived stigma in childhood epilepsy.

Developmental changes in autonomic emotional response during an executive functional task: A pupillometric study during Wisconsin card sorting test

OBJECTIVE The autonomic nervous system has a deep relationship with the cognitive network when performing cognitive tasks. We hypothesize that autonomic emotional responses can affect cognitive function, especially executive function. The aim of this study was to clarify the involvement of the autonomic system during an executive functional task via developmental changes assessed using pupillometry. SUBJECTS AND METHODS Subjects were 16 healthy children and 9 healthy adults. Children were divided into 3 groups (Group A, 7-9years; Group B, 10-14years; Group C, 15-17years). Pupil diameter was recorded using an eye mark recorder during cognitive shift (CS) during the Wisconsin card sorting test (WCST). The rate of pupil variations was integrated and compared within each group, focusing on performance during CS. RESULTS Categories achieved (CA) in the behavioral results of WCST increased with age, with significant differences between Group A and other groups. The change of pupillary diameter was increased with CS and decreased at the correct answers after CS in adults. Changes of pupillary diameter with CS showed a linear increase with age, and the pattern of the pupillary response at the age of 10-14years was comparable to adults. The integrated rate of pupil diameter with CS increased with age, and there was a significant difference between Group A and adults. In addition, the degree of mydriasis correlated with the number of CA. CONCLUSION These findings suggest that autonomic emotional response play an important role as a part of the process for executive function.

Efficacy of levetiracetam as first add-on therapy to carbamazepine and valproate sodium for children with epilepsy

We examined the effectiveness of levetiracetam (LEV) as add-on therapy after failed treatment with a first anti-epileptic drug in a prospective cohort of children with epilepsy. Eligible patients with epilepsy experienced uncontrolled seizures with the first anti-epileptic drug and were 1-15-year-old. Afte ra3m obaseline period, patients were administered LEV at an initial dose of 10 mg/kg/d, which, if needed, was incrementally increased by 5 mg/kg/d weekly up to a maximum dose of 60 mg/kg/d. Seizure frequency was defined as the mean seizure frequency per month. Clinical response to LEV over the following period of at least 6 mo was divided into five categories. A total of 37 patients were enrolled. The majority of patients (97.30%) had localization-related epilepsy. The responder rate (rate of patients with ≥50% reduction in seizure frequency) was 30/37 (81.08%). In addition, 20 of 37 (54.05%) patients showed complete seizure cessation. Mean percentage reduction in seizure frequency (all types of seizures) during the first 6 mo treatment period compared to baseline was 89.28% in responders, compared with 25.22% in non-responders. This proportion remained stable during the second 6 mo period (90.17%). Significant changes in seizure frequency were seen between before LEV administration and both the first 6 mo (P < 0.01) and second 6 mo (P < 0.01) in responders, but not in non-responders. Mean effective dose of LEV was 27.51 mg/kg/d. Somnolence was the only reported individual adverse event (5.41%), and was mild in all cases, so LEV discontinuation was not needed. LEV appears useful as a first add-on treatment in children with localization-related epilepsy.

Efficacy of levetiracetam for reducing rolandic discharges in comparison with carbamazepine and valproate sodium in rolandic epilepsy

PURPOSE The main purpose of this study was to compare the efficacy of levetiracetam (LEV) with the older antiepileptic drugs (AEDs) for preventing atypical evolution in children with Rolandic epilepsy (RE). Accordingly, the present study compared the efficacy of older AEDs (carbamazepine (CBZ) and valproate sodium (VPA)) with LEV in reducing rolandic discharges (RDs) on interictal electroencephalogram (EEG) in children with RE. METHODS Patients in this heterogenous study were subdivided into CBZ, VPA and LEV groups in accordance with the initial monotherapy. The CBZ and VPA groups were studied retrospectively, but the LEV group was studied prospectively. Appearances of discharges were counted and these rates were computed. In comparison with the baseline RD frequency, EEG response to AED treatment was classified such as complete disappearance and response (≥50% reduction in RD frequency). The time taken to attain complete disappearance or response in EEG responders was assessed for each AED treatment group. RESULTS Responders comprised 10 (11.2%) of the 89 patients treated with CBZ, 41 (56.2%) of the 73 patients with VPA, and 25 (71.4%) of the 35 patients with LEV. Mean interval to achievement of EEG response in the CBZ, VPA, and LEV groups were 36.3, 23.1, and 14.7 months, respectively. EEG response was achieved significantly more rapidly with LEV than with CBZ (p < 0.001) or VPA (p < 0.005). Seizure control was not significantly different in all 3 investigated drugs. CONCLUSIONS LEV seems to be superior to CBZ and VPA in its ability to suppress RDs in children with RE.

Association between seizure frequency and fatigue levels in children with epilepsy: Fatigue in children with epilepsy

The purpose of this study was to examine the association between seizure‐related features and fatigue levels in children with epilepsy.