Systematic review of the screening, diagnosis, and management of ADHD in children with epilepsy. Consensus paper of the Task Force on Comorbidities of the ILAE Pediatric Commission.

Attention-deficit/hyperactivity disorder (ADHD) is a common and challenging comorbidity affecting many children with epilepsy. A working group under the International League Against Epilepsy (ILAE) Pediatric Commission identified key questions on the identification and management of ADHD in children with epilepsy. Systematic reviews of the evidence to support approaches to these questions were collated and graded using criteria from the American Academy of Neurology Practice Parameter. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements were followed, with PROSPERO registration (CRD42018094617). No increased risk of ADHD in boys with epilepsy compared to girls with epilepsy was found (Level A). Valproate use in pregnancy is associated with inattentiveness and hyperactivity in offspring (1 class I study), and children with intellectual and developmental disabilities are at increased risk of ADHD (Level A). Impact of early seizure onset on development of ADHD was unclear (Level U), but more evident with poor seizure control (Level B). ADHD screening should be performed from 6 years of age, or at diagnosis, and repeated annually (Level U) and reevaluated after change of antiepileptic drug (AED) (Level U). Diagnosis should involve health practitioners with expert training in ADHD (Level U). Use of the Strength and Difficulties Questionnaire screening tool is supported (Level B). Formal cognitive testing is strongly recommended in children with epilepsy who are struggling at school (Level U). Behavioral problems are more likely with polytherapy than monotherapy (Level C). Valproate can exacerbate attentional issues in children with childhood absence epilepsy (Level A). Methylphenidate is tolerated and effective in children with epilepsy (Level B). Limited evidence supports that atomoxetine is tolerated (Level C). Multidisciplinary involvement in transition and adult ADHD clinics is essential (Level U). In conclusion, although recommendations could be proposed for some of the study questions, this systematic review highlighted the need for more comprehensive and targeted large-population prospective studies.

Effect of Levetiracetam Monotherapy in Nonlesional Focal Childhood Epilepsy.

This article compares the efficacy and tolerability of carbamazepine (CBZ) and levetiracetam (LEV) when used as initial monotherapy in children with nonlesional focal epilepsy. Patients with nonlesional focal epilepsy were subdivided into two groups according to the initial monotherapy: a LEV group administered LEV at an initial dose of 5 mg/kg/day and a CBZ group. Seizure response, adverse events, medication dose, reasons for discontinuing medication, adherence, and random serum levels were recorded. The overall percentage of patients who failed initial treatment and reasons for each treatment failure were determined. Data were analyzed from 183 children who received CBZ monotherapy and 46 children who received LEV monotherapy for ≥12 months. Overall, 126 patients (68.9%) became seizure-free with CBZ, compared with 37 patients (80.4%) with LEV. Moreover, four patients in CBZ and four patients in LEV groups showed a >50% reduction in seizure frequency. The efficacy rate was significantly higher and the adverse event rate was significantly lower in the LEV group than in the CBZ group (p = 0.0129 and p = 0.0039, respectively). LEV may offer superior efficacy and a lower risk of adverse effects compared with CBZ. LEV as initial monotherapy may represent a valuable treatment option for children with nonlesional focal childhood epilepsy.

Association between seizure frequency and fatigue levels in children with epilepsy.

AIM: The purpose of this study was to examine the association between seizure-related features and fatigue levels in children with epilepsy. METHODS: All children were classified into three subgroups based on the state of their seizure control: well-controlled epilepsy (WCE; seizure-free), intermediate-controlled epilepsy (ICE; seizure frequency < 1×/month) and uncontrolled epilepsy (UCE; seizure frequency > 1×/month). Participants were asked to rate on a 7-point scale, from 1 (strongly disagree) to 7 (strongly agree), how often they felt the ways described by nine items on the Fatigue Severity Scale (FSS). A higher score is suggestive of greater fatigue. RESULTS: The study participants comprised 58 children with epilepsy and 15 children without seizures, who served as the healthy (non-epilepsy) group. The mean FSS scores of the children with epilepsy were significantly higher than those of the healthy (non-epilepsy) group (4.40 vs. 1.55, respectively; P < 0.0001). Multiple linear regression analysis showed that seizure frequency was the only characteristic significantly associated with fatigue (P < 0.0001). In the three epilepsy subgroups, the mean FSS scores for the WCE, intermediate-controlled epilepsy and UCE groups were 2.30, 3.97 and 6.28, respectively. A higher seizure frequency was associated with more severe fatigue. In particular, children in the UCE group had significantly more severe fatigue than those in the WCE group (P < 0.0001). CONCLUSIONS: The results suggest that seizure frequency is also associated with fatigue in children with epilepsy. Improved control of seizures may help reduce fatigue levels and improve the quality of life of children with epilepsy.

[The efficacy of intravenous alendronate for osteoporosis in patients with severe motor intellectual disabilities].

Objective: Bone fractures in patients with severe motor and intellectual disabilities (SMIDs) have become an important problem to be solved. These fractures may result from disuse osteoporosis. Bisphosphonate administration is generally the most established treatment for patients with osteoporosis. However, traditional oral bisphosphonate use is associated with esophagitis as a side effect and may increase the risk of reflux esophagitis for bedridden patients. Intravenous alendronate, one of the bisphosphonates, was released in 2012 in Japan. Though it is appropriate for patients with SMIDs, there are no reports about the effects of intravenous alendronate on osteoporosis in SMID patients. Therefore, the efficacy of intravenous alendronate for osteoporosis was investigated in SMID patients. Methods: The subjects were 62 SMID patients with osteoporosis (20 to 60 years old) in our hospital. They were divided two groups, bisphosphonate treatment group (32 patients) and age-matched controls (30 patients). Patients in bisphosphonate treatment groups were given 900µg intravenous alendronate once a month. All patients were also administered oral vitamin D3. Serial bone density, bone metabolism markers, and existence of fractures were compared in both groups before and after treatment (6 months, 1 years, and 2 years). Results: In bisphosphonate treatment group, the change rate of bone density was significantly increased and bone metabolism markers were improved at 6 months and 1 year after starting treatment. After a year, 16 patients in treatment group changed into other treatments, and 12 controls started bisphosphonate treatment. In remaining treatment group (16 patients), the change rate of bone density and bone metabolism markers were improved significantly at 2 years after starting treatment. A patient in control group had a bone fracture, but no patients in bisphosphonate treatment groups had fractures or severe adverse effects. Conclusion: Intravenous alendronate is an effective treatment for osteoporosis in SMID patients.

Effect of Sunlight Exposure on Bone Mineral Density in Children with Severe Disability.

The aim of this study was to determine the efficacy of sunlight exposure for increasing bone mineral density (BMD) in children with severe disability. The subjects were five children with severe disability, aged 6 to 8 years. BMD was measured at baseline and after 3, 6, 9, and 12 months of starting sunlight exposure. All caregivers of patients were instructed to create opportunities to stay outdoors. Daily sunlight exposure time was defined as hours of staying outdoors. Mean hours of sunbathing per day were calculated at baseline and after 3, 6, 9, and 12 months of starting sunlight exposure. Sunlight exposure tended to be longer after starting than before starting in all patients, but the difference was not significant (p = 0.052). Along with the increase in sunlight exposure, BMD increased significantly after the start of sunlight exposure in all patients (p < 0.01). The serum values of total alkaline phosphatase and intact parathyroid hormone were significantly decreased and that of 25-hydroxyvitamin D was significantly increased 12 months after starting sunlight exposure. No patients had bone fractures after the start of sunlight exposure. These results suggest that sunlight exposure increased BMD, and that this may reduce the risk of bone fracture in children with disability.

Seizure severity in children with epilepsy is associated with their parents' perception of stigma.

AIMS: To develop and implement interventions to improve the quality of life (QOL) in children with epilepsy, it is important for clinicians and researchers to understand the effects of the children's parents' perception of stigma. The purpose of this study was to identify a relationship between patient clinical characteristics and perception of stigma in the parents of children with epilepsy. METHODS: Parents of children with epilepsy were recruited from our university hospital between April 1, 2005 and March 31, 2012. Items for the Parent Stigma Scale were developed from the literature and open-ended interviews with parents of children with epilepsy about their concerns and fears, including those related to stigma. Parents were asked to respond to five items, each on a 5-point scale from 1 (strongly disagree) to 5 (strongly agree). Assessments were performed for each clinical characteristic, such as child's sex, age at seizure onset, family history of epilepsy, seizure frequency, presence of status epilepticus (SE), presence of treatment-related adverse events, and the scores of each scale. RESULTS: A total of 52 parents of children with epilepsy and 10 parents of healthy children were enrolled in the study. Parents of children with epilepsy showed significantly higher scores on the questionnaire than parents of healthy children. In multiple regression analysis, greater perceptions of stigma were associated with a seizure frequency of more than one per month (p=0.0036, B=1.104, ß=0.402). In contrast, the presence of prior febrile seizures (p=0.0034, B=-1.297, ß=-0.308) and family history of epilepsy (p=0.0066, B=-1.613, ß=-0.277) were associated with lower perceptions of stigma. Greater parental perceptions of stigma were seen with the presence of monthly seizures. CONCLUSIONS: Parents of children with epilepsy are at risk of significant perceptions of stigma. Seizure severity, indicated by the presence of monthly seizures, was associated with greater perceptions of stigma in parents. In addition, the presence of prior febrile seizures and family history of epilepsy were associated with fewer perceptions of stigma. The findings of this study emphasize the importance of acknowledging and addressing parental perceptions of stigma.

A case of acute encephalopathy presenting with transient functional disability in various new tasks and hypoperfusion of the right frontal and temporal lobes on SPECT.

We report the case of a 5-year-old boy with acute encephalopathy presenting with transient executive dysfunction such as functional disability in various new tasks and hypoperfusion of the right frontal and temporal lobes on single photon emission tomography (SPECT). He presented with a 2-day history of disturbed consciousness, and electroencephalography in an awaked state showed diffuse high-voltage slow waves. Although MRI did not show any abnormality 3 days after initial onset of illness, SPECT showed hypoperfusion of the right frontal and temporal lobes at the same time. At 20 days after onset, the Kaufman assessment battery for children (K-ABC) test showed that sequential processing scale scores were significantly lower than simultaneous processing scale and achievement scale scores. He showed transient executive dysfunction such as functional disability in various new tasks at the same time. Abnormal brain perfusion on SPECT was improved at 8 months after onset and the sequential processing scale of K-ABC was likewise improved at 12 months after onset. These findings suggest that SPECT is helpful for diagnosing pathophysiological mechanisms with acute encephalopathy, and the combination of neuropsychological examination and SPECT study is useful for evaluating higher brain dysfunctions such as executive dysfunction.

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.

Risk factors for seizure recurrence in children after first unprovoked seizure.

BACKGROUND: 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. METHODS: Participants were recruited between 1 July 1997, and 30 June 2009. Eligible candidates were children between 1 month and 15 years old who presented with their first unprovoked afebrile seizure. After enrollment, recurrence of seizures was investigated. All participants were followed for at least 2 years. Log-rank test was used for bivariate analysis to check associations, and hazard ratios were used to analyze variables and clinical outcome (recurrence) during follow-up. RESULTS: Of 73 subjects, 42 (57.5%) experienced recurrence. The overall product-limit estimate of recurrence was 61.9% at 6 months, 85.7% at 1 year, and 95.2% at 2 years after seizure onset, respectively. Incidence of recurrence with partial and generalized seizures was 69.0% and 31.0%, respectively. Children with partial seizures had recurrence significantly more often than those with generalized seizures (P < 0.001). Recurrent seizures occurred after normal findings on electroencephalogram (EEG) in 21.4%, after generalized spike-and-wave complexes in 16.7%, and after focal epileptic discharge in 61.9%. Children with focal epileptic discharge had recurrence significantly more often than children with normal EEG findings (P < 0.001). CONCLUSION: The time to seizure recurrence after first unprovoked seizure may be within 1 year, and particularly within 6 months; and partial seizure and abnormal EEG with focal epileptic discharge may be risk factors for seizure recurrence.

[Effects of topiramate on headache in children with epilepsy].

OBJECTIVES: The purpose of the present study was to evaluate the efficacy and safety of topiramate (TPM) on inter-ictal headache in children with epilepsy. METHODS: Patients were interviewed regarding whether they suffered from headaches. Data obtained from each patient included seizure frequency. Inter-ictal headache was defined as a headache beginning outside an hour before or after the seizure. The study group included 85 outpatients (42 valproate-treated, 34 carbamazepine-treated, 6 combination therapy, 3 other) between 5 and 15 years old. For children with headache, TPM was administered twice daily at a total initial dose of 0.5 mg/kg/day, up to 3.0 mg/kg/day in accordance with symptoms. RESULTS: Of 85 patients, 18 (21.2%) patients (8 valproate-treated, 6 carbamazepine-treated, 3 combination therapy, and 1 other) complained of inter-ictal headache. Seizure frequency was significantly higher in children with headache (2.6 times/year) than in children without headache (0.9 times/year; p < 0.0001). The responder rate (rate of patients with a > 50% reduction in headache frequency or degree) was 13/18 (72%). Six children (33.3%) achieved complete cessation for the entire 6 months. Mean dose of TPM was significantly lower in responders (1.1 mg/kg/day) than in non-responders (2.7 mg/kg/day; p < 0.001). CONCLUSIONS: Headache is encountered more frequently in patients with frequent seizures. In addition, TPM represents a useful addition to the treatments available for headache in children with epilepsy. The effective dose of TPM for headache may be lower than that for seizure.

[Evaluation of quality of life in attention-deficit hyperactivity disorder children without comorbidity].

OBJECT: Improving quality of life (QOL) is one of the most important therapeutic goals for children with attention-deficit hyperactiv- ity disorder (AD/HD). The aim of this study was to measure QOL in AD/HD children without comorbidity and to examine associations between QOL and clinical symptoms of AD/HD for targeting early intervention. METHODS: Twenty-two enrolled patients and their parents completed the Questionnaire for Measuring Health-Related Quality of Life in Children (KINDL-R). Patients and teachers completed AD/HD rating scale-IV. Associations between QOL and clinical symptoms were assessed using t tests and correlations. RESULTS: Mean total score of the self-reported KINDL-R was 70.8. No difference in total QOL score was seen between AD/HD children and controls; however, the self-esteem subscale rated by AD/HD children was significantly higher than that of controls (p < 0.001). Total KINDL-R score correlated negatively with AD/HD rating scale-IV rated by teachers (p < 0.05). A difference was observed between AD/HD children in a lower QOL group and their parents in a subscale regarding QOL at school. CONCLUSIONS: These findings suggest that evaluation of QOL in AD/HD children without comorbidity is useful for identifying AD/HD children who might benefit from early intervention.

Therapeutic Strategies in Children with Epilepsy: A Quality-of-Life-Related Perspective.

Back ground: Children with epilepsy are affected by several factors, including clinical and social variables. Among these variables, cognitive decline and behavioral disturbances, perceptions of stigma, and fatigue can lead to reductions in quality of life (QOL). Epileptic activities, including seizure severity, frequent seizures, and status epilepticus (SE), have been identified as important predictors of QOL. In addition, the frequency of interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) may also be an important predictor of QOL, because IEDs can lead to cognitive decline and behavioral disturbances. Moreover, frequent seizures and/or IEDs may play a role in emotional mediators, such as stigma and fatigue, in childhood epilepsy. Seizure severity and/or IEDs are, therefore, important QOL-related factors in childhood epilepsy. Seizure severity as a QOL-related factor: Frontal lobe dysfunctions, such as cognitive decline and behavioral disturbances, can result in reduced QOL for both the child and their family. Frontal and prefrontal lobe growth disturbances can be present during active-phase epilepsy in some children with neuropsychological impairments. Recovery from prefrontal lobe growth disturbances may depend on the active seizure period. Children with a shorter active seizure period can recover from disturbances in prefrontal lobe growth more rapidly. In contrast, recovery may be delayed in children with a longer active seizure period. Moreover, frequent seizures can lead to seizure-associated headaches, perceptions of self-stigma and parental stigma, and fatigue. Accordingly, severe seizures can lead to neuropsychological impairments in association with prefrontal lobe growth disturbances in children with epilepsy. EEG abnormalities as QOL-related factors: IEDs on EEG, representing persistent pathological neuronal discharges, may be associated with several pathological aspects. Frontal IEDs can be a risk factor for recurrent seizures, cognitive decline, and behavioral disturbances, and they may also play a role as emotional mediators similar to stigma. In addition, behavioral disturbances may result in the presence of secondary bilateral synchrony (SBS) on EEG. Behavioral disturbances can be improved in association with a reduction in IEDs in children with frontal IEDs and SBS. Therefore, EEG abnormalities, such as frontal IEDs and SBS, can also lead to neuropsychological impairments in children with epilepsy. Therapeutic strategies in children with epilepsy: Seizure severity and IEDs on EEG may be associated with neuropsychological impairments, leading to QOL reduction. Therapeutic management may be desirable to reduce seizures and EEG abnormalities, such as frontal IEDs and SBS, as early as possible to improve QOL in children with epilepsy. During antiseizure medication (ASM) selection and adjustment, physicians should strategize the therapeutic approach to controlling seizures and suppressing EEG abnormalities in children with epilepsy. Among various ASMs, novel ASMs, such as levetiracetam and perampanel, may suppress both clinical seizures and IEDs on EEG; thus, these novel ASMs may represent an important addition to the treatments available for epileptic children presenting with frontal IEDs and SBS.

Steroid-Responsive Involuntary Movements as a Remote Symptom of Febrile Infection-Related Epilepsy Syndrome.

Febrile infection-related epilepsy syndrome (FIRES) is a rare epileptic encephalopathy that occurs in children or adolescents. To date, evidence for the management of the post-acute phase of FIRES is focused on drug-resistant epilepsy that continues from the acute phase. Information on involuntary movements, which are newly developed in the chronic phase, is limited. We report a 13-year-old boy, who had a history of FIRES at nine years of age and experienced worsening seizure control that was accompanied by unremitting involuntary　movements after two years of a fairly controlled period. The involuntary movements resulted in motor deterioration and forced him to be bedridden. Although no neuronal autoantibodies were detected, we hypothesized that the boy's neurological deterioration was triggered by an autoimmune response based on the elevation of serum anti-glutamic acid decarboxylase and serum anti-thyroid peroxidase antibodies and hypermetabolism of bilateral lenticular nuclei on 18-fluorodeoxyglucose positron emission tomography that resembled those reported in patients with other types of autoimmune encephalitis. Serial methylprednisolone pulse therapy and intravenous immunoglobulin therapy ameliorated involuntary movements and improved his activities of daily living. Late-onset involuntary movements, along with seizure exacerbation, may appear in the chronic phase of FIRES. Immunotherapy could be effective in treating these symptoms.

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.

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

BACKGROUND: 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. METHODS: The questionnaire was divided into three parts: details of the child and their family; medical management of the child before reaching hospital; and parental thoughts and actions when the child experienced convulsions. RESULTS: Parents without prior knowledge of FS showed a higher rate of thinking that FS were harmful than parents with prior knowledge (P < 0.03). Parents with prior knowledge were aware that their child was having an FS at a higher rate than parents without prior knowledge (P < 0.001). Moreover, parents without prior knowledge managed the convulsions less appropriately than parents with prior knowledge (P < 0.03). CONCLUSIONS: Parental fears that the death of their child was imminent and the misperception of FS as a serious, life-threatening condition indicate a lack of knowledge regarding FS. Organizing parental support groups and effective educational intervention programs for parents should be given priority in the care of children with FS.

Effect of Lacosamide on Interictal Epileptiform Discharges in Pediatric Patients With Newly Diagnosed Focal Epilepsy.

BACKGROUND: The purpose of this study was to determine the efficacy of lacosamide (LCM) on interictal epileptiform discharges (IEDs) and evaluate the relationships between IEDs and seizure outcome in pediatric patients with focal epilepsy. METHODS: Patient inclusion criteria included (1) newly diagnosed focal epilepsy with unknown etiology; and (2) electroencephalogram recorded twice (before and after starting LCM) under the same conditions. The difference between the highest number of IEDs over five successive minutes (IEDs/5 min) and the location of IEDs was determined. Seizure outcome was evaluated one year after achieving the maintenance dose of LCM. Responders were identified as showing a ≥50% reduction in the pre-LCM seizure frequency. RESULTS: Of 22 patients, 10 showed an increase in IEDs/5 min after starting LCM. The median IEDs/5 min before and after starting LCM was not significantly different, at 1.5 (interquartile range: 0, 31.75) and 10.5 (0, 80.5), respectively. No relationship was identified between the difference in IEDs/5 min and seizure outcome. Patients with multiple regional or diffuse IEDs had significantly poorer seizure outcome compared with patients without those IEDs (P = 0.036 and P = 0.039, respectively). Of 10 patients with single regional IEDs, a tendency of IEDs to disappear was observed between patients with frontal and non-frontal IEDs. CONCLUSION: The effects of LCM on the number of IEDs may be unrelated to seizure outcome. LCM may be ineffective at improving seizure outcomes in patients with multiple regional or diffuse IEDs.

Evaluating Dysfunction in Fever-Induced Paroxysmal Weakness and Encephalopathy.

Heterozygous variants in the ATP1A3 gene are linked to well-known neurological phenotypes. There has been growing evidence for a separate phenotype associated with variants in residue Arg756-fever-induced paroxysmal weakness and encephalopathy (FIPWE) or relapsing encephalopathy with cerebellar ataxia (RECA). With only about 20 cases being reported, the clinical features associated with mutations at Arg756 have not been fully elucidated. We report a case of FIPWE with a p.Arg756Cys change in the ATP1A3 gene and a comparison of the clinical features, including electrophysiological examination, with previous cases. The 3-year-old male patient had normal psychomotor development, presenting with recurrent symptoms of generalized hypotonia with loss of gait, mutism, and dystonic movements only during febrile illnesses since 19 months of age. At 2.7 years of age, a third neurological decompensation episode occurred, during which electroencephalography (EEG) did not reveal high voltage slow waves or epileptiform discharge. Nerve conduction studies (NCS) also did not show latency delay or amplitude reduction. ATP1A3 exon sequencing showed a heterozygous p.Arg756Cys mutation. While the patient experienced repeated encephalopathy-like episodes, including severe hypotonia during febrile illness, EEG and NCS did not reveal any obvious abnormalities. These electrophysiological findings may represent an opportunity to suspect FIPWE and RECA.

Factors associated with the development of epilepsy in very low birth weight infants.

BACKGROUND: The survival rate of very low birth weight (VLBW) infants has recently improved. However, the occurrence of and factors associated with epilepsy in VLBW infants remain unknown. This study aimed to clarify the incidence, characteristics, and factors associated with epilepsy development in VLBW infants. METHODS: All VLBW infants admitted to our hospital between 2012 and 2017 were included in this study. VLBW infants with a follow-up period of <1 year were excluded. Chromosomal abnormalities, brain anomalies, severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and hypoxic ischemic encephalopathy (HIE) were considered to be risk factors. RESULTS: Epilepsy occurred in 21/526 (4.0%) VLBW infants. Chromosomal abnormalities, brain anomalies, severe IVH, cystic PVL, HIE, neonatal seizures, advanced maternal age, maternal diabetes mellitus, no administration of antenatal corticosteroids, and low Apgar scores at 1 and 5 min were associated with a risk of epilepsy. The median time to epilepsy onset was 8 months (range: 0-59 months), and the onset occurred within 2 years in 15/21 patients (71.4%) and within 4 years in 18/21 patients (85.7%). VLBW infants with risk factors developed epilepsy earlier and at a significantly higher rate than those without risk factors. Among infants who had risk factors and who developed epilepsy, 86.7% did so within 2 years of age, compared to 33.3% of those who developed epilepsy but did not have risk factors. CONCLUSION: These findings regarding factors associated with a risk of development of epilepsy and temporal feature of epilepsy may contribute to the development of monitoring and treatment protocols for epilepsy in VLBW infants.

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. METHODS: The rolandic epilepsy group consisted of 10 children (mean age 5y 6mo, SD 1y 1mo, median age 5y 5mo; six males, four females). The ABPE group comprised five children (mean age 5y, SD 1y 2mo, median age 4y 5mo; three males, two females). We recorded the number of spikes, the locations of spikes, and the duration of the spike activity. The Wechsler Intelligence Scale for Children-Third Edition or the Wechsler Preschool and Primary Scale of Intelligence, depending on age, was administered to all children at the onset of seizures and every year thereafter. The diagnosis of attention-deficit-hyperactivity disorder was made according to the DSM-IV. RESULTS: Significant correlations were found between atypical clinical features and extended periods of high-frequency paroxysmal EEG abnormalities (>24mo after onset; p<0.01) and frontal EEG focus (>10mo after onset; p<0.003). INTERPRETATION: A combination of spike rate and extended periods of high-frequency paroxysmal EEG abnormalities may predict the evolution of atypical rolandic epilepsy.