Clinical outcomes of intensive versus less intensive first-line chemotherapy for metastatic colorectal cancer.

Aims: Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Materials & methods: Data were collected from a medical claims database. The efficacy outcomes were: time to treatment failure, time to first subsequent therapy and overall survival. Results: The less intensive therapy group (n = 633) had higher median age, lower daily activity levels and shorter time to treatment failure, time to first subsequent therapy and overall survival than the intensive therapy group (n = 3829). Combination therapy with molecularly targeted agents and bevacizumab improved treatment efficacy outcomes in the intensive and less intensive groups, respectively. Conclusion: Patient age and daily activity levels were important factors for determining treatment intensity.

In this study we performed a real-world data analysis of treatment for advanced colorectal cancer that had spread to other parts of patients' bodies, by investigating the medical records of 4462 patients. We wanted to see how well different treatments worked and what kinds of patients received them. We found that the most important factors when choosing between different treatments were the patient's age and how well they could perform their everyday tasks. We found that using specialized medicines in the intensive treatment group, and a drug called bevacizumab in the less intensive group, resulted in better patient outcomes.

Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome.

Neonatal diabetes mellitus (NDM) with developmental delay and epilepsy is classified as developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. The majority of DEND syndrome are due to severely damaging variants of K-ATP channels, and few mitochondria-related genes have been reported. We report here two Japanese siblings who were clinically diagnosed with DEND syndrome in whom NARS2 compound heterozygous variants were detected. Patient 1 was a 3-year-old girl and presented with diabetes ketoacidosis at 3 months old. Patient 2 was a 1-year-old boy who presented with severe hyperglycemia and started insulin therapy at 3 days old. After the first episodes, they both presented with severe developmental delay, hearing loss and treatment-resistant epilepsy accompanied by progressive brain atrophy. Whole-exome sequencing revealed compound heterozygous NARS2 p.R159C and p.L217V variants, and the GATA4 p.P407Q variant in both patients. They were treated by mitochondrial supportive therapy of vitamin B1, L-carnitine, and coenzyme Q10. Patient 2 was withdrawn from insulin therapy at 6 months old. This is the first report of NDM in which variants of the NARS2 gene coding mitochondrial protein were detected. Genetic analysis including mitochondrial genes should be considered in patients with neonatal onset diabetes associated with neurogenic symptoms.

Abnormal Ca2+ Signals in Reactive Astrocytes as a Common Cause of Brain Diseases.

In pathological brain conditions, glial cells become reactive and show a variety of responses. We examined Ca2+ signals in pathological brains and found that reactive astrocytes share abnormal Ca2+ signals, even in different types of diseases. In a neuropathic pain model, astrocytes in the primary sensory cortex became reactive and showed frequent Ca2+ signals, resulting in the production of synaptogenic molecules, which led to misconnections of tactile and pain networks in the sensory cortex, thus causing neuropathic pain. In an epileptogenic model, hippocampal astrocytes also became reactive and showed frequent Ca2+ signals. In an Alexander disease (AxD) model, hGFAP-R239H knock-in mice showed accumulation of Rosenthal fibers, a typical pathological marker of AxD, and excessively large Ca2+ signals. Because the abnormal astrocytic Ca2+ signals observed in the above three disease models are dependent on type II inositol 1,4,5-trisphosphate receptors (IP3RII), we reanalyzed these pathological events using IP3RII-deficient mice and found that all abnormal Ca2+ signals and pathologies were markedly reduced. These findings indicate that abnormal Ca2+ signaling is not only a consequence but may also be greatly involved in the cause of these diseases. Abnormal Ca2+ signals in reactive astrocytes may represent an underlying pathology common to multiple diseases.

Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders.

Astrocytes are abundant cells in the brain that regulate multiple aspects of neural tissue homeostasis by providing structural and metabolic support to neurons, maintaining synaptic environments and regulating blood flow. Recent evidence indicates that astrocytes also actively participate in brain functions and play a key role in brain disease by responding to neuronal activities and brain insults. Astrocytes become reactive in response to injury and inflammation, which is typically described as hypertrophy with increased expression of glial fibrillary acidic protein (GFAP). Reactive astrocytes are frequently found in many neurological disorders and are a hallmark of brain disease. Furthermore, reactive astrocytes may drive the initiation and progression of disease processes. Recent improvements in the methods to visualize the activity of reactive astrocytes in situ and in vivo have helped elucidate their functions. Ca2+ signals in reactive astrocytes are closely related to multiple aspects of disease and can be a good indicator of disease severity/state. In this review, we summarize recent findings concerning reactive astrocyte Ca2+ signals. We discuss the molecular mechanisms underlying aberrant Ca2+ signals in reactive astrocytes and the functional significance of aberrant Ca2+ signals in neurological disorders.

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.

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.

Disease-relevant upregulation of P2Y1 receptor in astrocytes enhances neuronal excitability via IGFBP2.

Reactive astrocytes play a pivotal role in the pathogenesis of neurological diseases; however, their functional phenotype and the downstream molecules by which they modify disease pathogenesis remain unclear. Here, we genetically increase P2Y1 receptor (P2Y1R) expression, which is upregulated in reactive astrocytes in several neurological diseases, in astrocytes of male mice to explore its function and the downstream molecule. This astrocyte-specific P2Y1R overexpression causes neuronal hyperexcitability by increasing both astrocytic and neuronal Ca2+ signals. We identify insulin-like growth factor-binding protein 2 (IGFBP2) as a downstream molecule of P2Y1R in astrocytes; IGFBP2 acts as an excitatory signal to cause neuronal excitation. In neurological disease models of epilepsy and stroke, reactive astrocytes upregulate P2Y1R and increase IGFBP2. The present findings identify a mechanism underlying astrocyte-driven neuronal hyperexcitability, which is likely to be shared by several neurological disorders, providing insights that might be relevant for intervention in diverse neurological disorders.

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.

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.