Exploration of urine metabolic biomarkers for new-onset, untreated pediatric epilepsy: A gas and liquid chromatography mass spectrometry-based metabolomics study.

OBJECTIVE: The discovery of objective indicators for recent epileptic seizures will help confirm the diagnosis of epilepsy and evaluate therapeutic effects. Past studies had shortcomings such as the inclusion of patients under treatment and those with various etiologies that could confound the analysis results significantly. We aimed to minimize such confounding effects and to explore the small molecule biomarkers associated with the recent occurrence of epileptic seizures using urine metabolomics. METHODS: This is a multicenter prospective study. Subjects included pediatric patients aged 2 to 12 years old with new-onset, untreated epilepsy, who had had the last seizure within 1 month before urine collection. Controls included healthy children aged 2 to 12 years old. Those with underlying or chronic diseases, acute illnesses, or recent administration of medications or supplements were excluded. Targeted metabolome analysis of spot urine samples was conducted using gas chromatography (GC)- and liquid chromatography (LC)-tandem mass spectrometry (MS/MS). RESULTS: We enrolled 17 patients and 21 controls. Among 172 metabolites measured by GC/MS/MS and 41 metabolites measured by LC/MS/MS, only taurine was consistently reduced in the epilepsy group. This finding was subsequently confirmed by the absolute quantification of amino acids. No other metabolites were consistently altered between the two groups. CONCLUSIONS: Urine metabolome analysis, which covers a larger number of metabolites than conventional biochemistry analyses, found no consistently altered small molecule metabolites except for reduced taurine in epilepsy patients compared to healthy controls. Further studies with larger samples, subjects with different ages, expanded target metabolites, and the investigation of plasma samples are required.

Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma.

West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity.

Incidence and risk factors of acute encephalopathy with biphasic seizures in febrile status epilepticus.

OBJECTIVE: To clarify the incidence and risk factors of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in pediatric patients with febrile status epilepticus (FSE). METHODS: We retrospectively surveyed patients with FSE (≥20 min and ≥40 min) who were younger than 6 years by mailing a questionnaire to 1123 hospitals in Japan. The survey period was 2 years. We then collected clinical data on patients with prolonged febrile seizures (PFS) ≥40 min and those with AESD, and compared clinical data between the PFS and AESD groups. RESULTS: The response rate for the primary survey was 42.3%, and 28.0% of hospitals which had applicable cases responded in the secondary survey. The incidence of AESD was 4.3% in patients with FSE ≥20 min and 7.1% in those with FSE ≥40 min. In the second survey, a total of 548 patients had FSE ≥40 min (AESD group, n = 93; PFS group, n = 455). Univariate analysis revealed significant between-group differences in pH, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, NH3, procalcitonin (PCT), uric acid, blood urea nitrogen, creatinine (Cr), and lactate. Multivariate analysis using stratified values showed that high PCT was an only risk factor for AESD. A prediction score of ≥3 was indicative of AESD, as determined using the following indexes: HCO3- < 20 mmol/L (1 point), Cl <100 mEq/L (1 point), Cr ≥0.35 mg/dL (1 point), glucose ≥200 mg/dL (1 point), and PCT ≥1.7 pg/mL (2 points). The scoring system had sensitivity of 84.2% and specificity of 81.0%. CONCLUSION: Incidence data and prediction scores for AESD will be useful for future intervention trials for AESD.

Different pharmacoresistance of focal epileptic spasms, generalized epileptic spasms, and generalized epileptic spasms combined with focal seizures.

OBJECTIVE: Among standard treatments for infantile spasms, adrenocorticotropic hormone (ACTH) is reported as the best treatment, but ACTH is ineffective in one-half of the patients. To establish precision medicine, we examined pharmacoresistance of focal epileptic spasms (ES), generalized ES, and generalized ES combined with focal seizures, diagnosed based on the revised seizure classification of ILAE in 2017. METHODS: We conducted a retrospective nationwide study in Japan on the long-term seizure outcome of ES. Long-term seizure outcome was evaluated by seizure-free rate, seizure-free period, and Kaplan-Meier curve. Seizure-free was defined as seizure control for longer than 2 months. RESULTS: From the medical history of 501 patients, 325 patients had generalized ES only (GES group) at the start of the first treatment, 125 patients had generalized ES after focal seizure onset (FS-GES group), seven patients had focal ES after focal seizure onset (FS-FES group), and 24 patients had generalized ES combined with focal seizures after focal seizure onset (FS-GES + FS group). Seizure-free period of ES (generalized ES and focal ES) [mean (95% confidence interval)] was 2.7 (0.0-5.4) months in GES group, 1.1 (0.1-2.2) months in FS-GES group, 1.0 (0.2-1.9) months in FS-GES + FS group, and 0.1 (-0.2-0.5) months in FS-FES group. Seizure-free rate, seizure-free period, and Kaplan-Meier curve of generalized ES were almost the same in GES group and FS-GES group, with characteristics of superior response to ACTH. Mean seizure-free period of generalized ES combined with focal seizures was significantly shorter in FS-GES + FS group than in GES group. Mean seizure-free period of focal ES in FS-FES group was extremely short with exceedingly early relapse. SIGNIFICANCE: Pharmacoresistance was different in generalized ES, focal ES, and generalized ES combined with focal seizures. ES with focal features or with focal seizures may have focal lesions, thus consider surgical options earlier in the course.

Case Report: High-Gamma Oscillations on an Ictal Electroencephalogram in a Newborn Patient With Hypoxic-Ischemic Encephalopathy.

Fast oscillations (FOs) >40 Hz in electroencephalograms (EEGs) are associated with ictogenesis and epileptogenesis in adults and children with epilepsy. However, only a few previous studies showed FOs in neonates. Reported frequencies of such neonatal FOs were in the low-gamma (<60 Hz) band and, therefore, they were not high compared to those in pediatric patients. We herein report a newborn patient with severe hypoxic-ischemic encephalopathy (HIE), who showed pathological FOs with a frequency in the high-gamma band. She was born at a gestational age of 39 weeks 4 days by emergency cesarean section because of non-reassuring fetal status. She had focal motor seizures involving unilateral upper and lower limbs lasting for tens of seconds on days 0, 1, 4, 5, 8, and 9 and subclinical seizures on days 4-11. Phenobarbital (PB) was intravenously administered on days 0, 2, 4, 5, and 6. We found FOs that were superimposed on the ictal delta activities using visual inspection and time-frequency analysis on 8-11 days of age. Among them, we detected high-gamma (71.4-100 Hz) oscillations that appeared to be temporally independent of low-gamma activities in the ictal EEG on 11 days of age. To the best of our knowledge, this is one of the earliest reports showing pathological FOs with a frequency of >60 Hz in the high-gamma band in human neonatal seizures, which were previously observed in animal studies. Further studies are needed to elucidate the pathophysiology of ictal FOs in neonatal seizures.

Phenotypes of SMA patients retaining SMN1 with intragenic mutation.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous deletion or intragenic mutation of the SMN1 gene. It is well-known that high copy number of its homologous gene, SMN2, modifies the phenotype of SMN1-deleted patients. However, in the patients with intragenic SMN1 mutation, the relationship between phenotype and SMN2 copy number remains unclear. METHODS: We have analyzed a total of 515 Japanese patients with SMA-like symptoms (delayed developmental milestones, respiratory failures, muscle weakness etc.) from 1996 to 2019. SMN1 and SMN2 copy numbers were determined by quantitative polymerase chain reaction (PCR) method and/or multiplex ligation-dependent probe amplification (MLPA) method. Intragenic SMN1 mutations were identified through DNA and RNA analysis of the fresh blood samples. RESULTS: A total of 241 patients were diagnosed as having SMA. The majority of SMA patients showed complete loss of SMN1 (n = 228, 95%), but some patients retained SMN1 and carried an intragenic mutation in the retaining SMN1 (n = 13, 5%). Ten different mutations were identified in these 13 patients, consisting of missense, nonsense, frameshift and splicing defect-causing mutations. The ten mutations were c.275G > C (p.Trp92Ser), c.819_820insT (p.Thr274Tyrfs*32), c.830A > G (p.Tyr277Cys), c.5C > T (p.Ala2Val), c.826 T > C (p.Tyr276His), c.79C > T (p.Gln27*), c.188C > A (p.Ser63*), c.422 T > C (p.Leu141Pro), c.835-2A > G (exon 7 skipping) and c.835-3C > A (exon 7 skipping). It should be noted here that some patients with milder phenotype carried only a single SMN2 copy (n = 3), while other patients with severe phenotype carried 3 SMN2 copies (n = 4). CONCLUSION: Intragenic mutations in SMN1 may contribute more significantly to clinical severity than SMN2 copy numbers.

Hypertensive Cerebral Hemorrhage in a Patient with Turner Syndrome Caused by Deletion in the Short Arm of the X Chromosome.

Turner syndrome is a chromosomal disorder usually caused by complete deletion of an X chromosome, with deletion in the short arm of the X chromosome being a rare cause of the condition. Patients with Turner syndrome commonly develop hypertension, and associated vascular complications such as aortic dissection or cerebral hemorrhage have been reported. Cerebral hemorrhage in Turner syndrome is a rare complication, and only a few reports have been published. In these reports, all patients have XO karyotypes or a mosaic type as the cause of Turner syndrome, while no other Turner syndrome types have been documented. In this report, we present for the first time a patient with Turner syndrome caused by deletion in the short arm of the X chromosome who experienced hypertensive hemorrhage as a late complication.

Manifestation of both emetic seizures and sylvian seizures in the same patients with benign partial epilepsy.

PURPOSE: Benign childhood epilepsy with centro-temporal spikes (BECTS) and Panayiotopoulos syndrome (PS) have different pathophysiologies and show different types of seizures, yet they overlap in some important respects. In an attempt to understand the ways in which they differ from each other and overlap each other, we performed a detailed investigation on patients who had both characteristic types of seizure manifestations, namely, sylvian seizures and emetic seizures. SUBJECTS AND METHODS: We recruited consecutive subjects from the EEG database of outpatients who had visited our hospital between 2008 and 2010 and who had been diagnosed with BECTS or PS. As a result, 45 patients with BECTS and 50 patients with PS were selected from the database. Viewing the clinical records of these 95 patients, five patients were selected who had experienced both sylvian seizures and emetic seizures. Next, the clinical features and EEG findings of these five patients were retrospectively observed at the date of investigation: October 1, 2011. RESULTS: We found that all the patients showed rolandic spikes when they had sylvian seizures, and occipital spikes or multifocal spikes when they had emetic seizures. We also report in detail on one patient who showed two different types of ictal EEG patterns: one of which started in the occipital area and the other of which was located in the rolandic area. CONCLUSION: Based on these findings, we conclude that widespread cortical hyperexcitability that includes the occipital area is necessary to produce the autonomic seizure manifestations seen in PS.

High-frequency EEG activity in epileptic encephalopathy with suppression-burst.

OBJECTIVE: We explored high-frequency activity in the suppression-burst (SB) pattern of interictal electroencephalogram (EEG) in early infantile epileptic encephalopathy including Ohtahara syndrome (OS) and early myoclonic encephalopathy (EME) to investigate the pathophysiological characteristics of SB. METHODS: Subjects included six patients with the SB EEG pattern related to OS or EME (Group SB). The results were evaluated in comparison to tracé alternant (TA) observed during the neonatal period in nine patients to rule out possible nonspecific relationships between high-frequency activity and periodic EEG patterns (Group TA). EEG was digitally recorded with a sampling rate of 500Hz and the analysis was performed in each of the particular bipolar channel-pairs. We visually selected 20 typical consecutive burst sections and 160 inter-burst sections for comparison from the sleep record of each patient and performed the time-frequency analysis. We investigated the maximum frequencies of power enhancement in each derivation in both groups. RESULTS: In Group SB, a significant increase in power at a frequency of 80-150Hz was observed in association with the bursts, particularly in the bilateral parieto-occipital derivations, in all patients. In Group TA, on the contrary, no significant increase in high-frequency power was found. The maximum frequencies of power enhancement were significantly higher in Group SB than in Group TA (p<0.001 by repeated-measures ANOVA). CONCLUSION: Interictal high frequencies of up to 150Hz were detected in the suppression-burst EEG patterns in epileptic encephalopathy in early infancy. Further studies will be necessary to identify the role of the interictal high-frequency activity in the pathophysiology of such early epileptic encephalopathy.

Five pediatric cases of ictal fear with variable outcomes.

PURPOSE: Ictal fear is an uncommon condition in which fear manifests as the main feature of epileptic seizures. The literature has suggested that ictal fear is generally associated with poor seizure outcomes. We wanted to clarify the variability in seizure outcome of children with ictal fear. SUBJECTS AND METHODS: We identified five pediatric patients with ictal fear who were followed up on at Okayama University Hospital between January 2003 and December 2012. We retrospectively reviewed their clinical records and EEG findings. RESULTS: The onset age of epilepsy ranged from 8 months to 9 years and 10 months. The common ictal symptoms were sudden fright, clinging to someone nearby, and subsequent impairment of consciousness, which were often accompanied by complex visual hallucinations and psychosis-like complaints. Ictal fear, in four patients, was perceived as a nonepileptic disorder by their parents. Ictal electroencephalograms (EEG) of ictal fear were obtained in all patients. Three showed frontal onset, while the other two showed centrotemporal or occipital onsets. Two patients were seizure free at last follow-up, while seizures persisted in the other three. A patient with seizure onset during infancy had a favorable outcome, which was considered to be compatible with benign partial epilepsy with affective symptoms. CONCLUSION: Ictal fear is not always associated with a symptomatic cause or a poor seizure outcome. It is quite important to make a correct diagnosis of ictal fear as early as possible to optimize treatment.

Inhalation of 10% carbon dioxide rapidly terminates Scn1a mutation-related hyperthermia-induced seizures.

The aim of this study was to assess the anticonvulsant effect of carbon dioxide (CO2) on Scn1a mutation-related febrile seizures. We examined physiological changes in the blood gas levels after the induction of hyperthermia-induced seizures (HISs), which were associated with the Scn1a missense mutation. We determined the efficacy of inhalation of 5% or 10% CO2 to treat HISs. HISs were evoked in Scn1a mutant and wild-type (WT) rats by hot water baths. To determine the anticonvulsant effect of CO2 inhalation, rats were placed in a chamber filled with air or mixed gas containing 5% CO2 or 10% CO2 for 3 min, immediately after the induction of HISs. We also analyzed the blood gas levels at the end of inhalation of CO2. Hot water bathing induced a significant reduction in the partial pressure of CO2 (pCO2) and respiratory alkalosis in the WT and Scn1a mutant rats. HISs were evoked in 100% of the Scn1a mutant rats within 5 min, but in none of the WT rats. The Scn1a mutant rats demonstrated a higher HISs susceptibility associated with respiratory alkalosis than the WT rats. Inhalation of 10% CO2 shortened the seizure duration from 62.6±12.1 s to 15.5±1.0 s. Blood gas analysis after the inhalation of 10% CO2 demonstrated an elevated pCO2 level and respiratory acidosis. Inhalation of 10% CO2 demonstrated a potent and fast-acting anticonvulsant effect against HISs.

High-frequency EEG oscillations in hyperthermia-induced seizures of Scn1a mutant rats.

We examined high-frequency oscillations (HFOs) in the ictal cortical EEGs of hyperthermia-induced seizures in a rat model of febrile seizures with an SCN1A mutation as a means of investigating the pathophysiological mechanisms underlying the generation of febrile seizures. We used 13 male homozygous Scn1a-N1417H mutant rats (F344/NSlc-Scn1a(Kyo811)) and 10 wild-type control rats. Generalized tonic-clonic seizures were induced in all mutant rats, and HFOs with frequencies ranging from 200 to 400 Hz were found to precede spikes during the clonic phases of these seizures in the ictal EEGs. The proportion of all spikes in each seizure that were associated with HFOs increased with age. In time-frequency spectra of the EEG data, the HFOs had a mean peak frequency of 301.1 ± 65.4 Hz (range: 156.3-468.8Hz) and a mean peak power of 24.6 ± 3.8 dB (range: 11.4-33.4 dB); the peak power increased with age. Regarding the wild-type rats, a brief seizure without unmistakable HFOs was exceptionally induced in only one rat. The generation mechanism of febrile seizures is still an unanswered question. The detection of HFOs from the ictal EEGs of hyperthermia-induced seizures may provide a cue to answering this open question, although in this research we were unable to provide sufficient evidence to prove that the generation of HFOs depended on the mutation.

Effects of intravenous diazepam on high-frequency oscillations in EEGs with CSWS.

High-frequency oscillations (HFOs) associated with continuous spike-waves during slow-wave sleep (CSWS) are speculated to be linked to the disturbance of higher brain function. We intended to investigate the generative mechanisms of HFOs in CSWS by clarifying the effects of intravenous injection (IV) of diazepam (DZP), an agonist for the gamma-aminobutyric acid A (GABAA) receptor in the GABAergic interneuron system, in patients who had previously been treated with IV DZP. The subjects were three patients with epilepsy with CSWS. For each patient, EEG data before and after IV DZP were separated into consecutive 5-min sections. Time-frequency power spectral analysis was performed on the spikes of each section, and peak-power and frequency of detected high-frequency spectral spots were compared before and after IV DZP. Spectral spots with peak-frequencies at 85.9-121.1Hz in the ripple band were revealed in all three patients. Although the amplitudes of the spikes largely returned to the baseline levels 20-25min after IV DZP, the recovery of the peak-power levels of HFOs lagged behind that of the spike amplitudes, and the power levels of HFOs were lower than the baseline data within 25min after the injection of DZP. No consistent changes were found regarding the spectral frequencies of HFOs. The dissociation of the effect of IV DZP in terms of recovery when comparing spike-amplitudes and the power of HFOs may correspond to an already suggested difference in the pathophysiological mechanisms that generate the spikes and HFOs.

Amplitude-integrated EEG colored according to spectral edge frequency.

OBJECTIVE: To improve the interpretability of figures containing an amplitude-integrated electroencephalogram (aEEG), we devised a color scale that allows us to incorporate spectral edge frequency (SEF) information into aEEG figures. Preliminary clinical assessment of this novel technique, which we call aEEG/SEF, was performed using neonatal and early infantile seizure data. METHODS: We created aEEG, color density spectral array (DSA), and aEEG/SEF figures for focal seizures recorded in seven infants. Each seizure was paired with an interictal period from the same patient. After receiving instructions on how to interpret the figures, eight test reviewers examined each of the 72 figures displaying compressed data in aEEG, DSA, or aEEG/SEF form (12 seizures and 12 corresponding interictal periods) and attempted to identify each as a seizure or otherwise. They were not provided with any information regarding the original record. RESULTS: The median number of correctly identified seizures, out of a total of 12, was 7 (58.3%) for aEEG figures, 8 (66.7%) for DSA figures and 10 (83.3%) for aEEG/SEF figures; the differences among these are statistically significant (p=0.011). All reviewers concluded that aEEG/SEF figures were the easiest to interpret. CONCLUSION: The aEEG/SEF data presentation technique is a valid option in aEEG recordings of seizures.

High-frequency oscillations in idiopathic partial epilepsy of childhood.

PURPOSE: We explored high-frequency oscillations (HFOs) in scalp sleep electroencephalography (EEG) studies of patients with idiopathic partial epilepsy (IPE) of childhood in order to obtain a better understanding of the pathologic mechanisms underlying IPE. METHODS: The subjects were 45 patients, including 32 with benign childhood epilepsy with centrotemporal spikes (BCECTS) and 13 with Panayiotopoulos syndrome (PS). A total of 136 EEG records were investigated through temporal expansion and filtering of traces and time-frequency spectral analysis. KEY FINDINGS: HFOs with frequency of 93.8-152.3 Hz (mean 126.2 ± 13.6 Hz) in the band of ripples were detected in association with spikes in 97 records (71.3%). Time from last seizure to the EEG recording was significantly shorter in those with spike-related HFOs than in the EEG recordings with spikes without HFOs (p = 0.006). Although time from last seizure reflects age, age at the time of recording was not significantly different between EEG studies with and without HFOs. Peak-power values of the high-frequency spots in time-frequency spectra were significantly negatively correlated with time from last seizure (R(2) = 0.122, p < 0.001) but not with age at the time of recording. Peak frequencies of the high-frequency spectral spots were not significantly correlated with age at the time of recording or with time from last seizure. SIGNIFICANCE: The close relationship between the generation of spike-related HFOs and the period of active seizure occurrence indicated that HFOs may tell us more about epileptogenicity in IPE than the spikes themselves. Because there is a spectrum of pediatric epileptic disorders extending from the benign end of BCECTS to the encephalopathic end of epilepsy with continuous spike-waves during slow-wave sleep (CSWS), and HFOs that have already been detected in association with CSWS were more prominent than HFOs in IPE, intense spike-related HFOs may indicate poor prognosis.

Scalp-recorded high-frequency oscillations in childhood sleep-induced electrical status epilepticus.

Because high-frequency oscillations (HFOs) may affect normal brain functions, we examined them using electroencephalography (EEG) in epilepsy with continuous spike-waves during slow-wave sleep (CSWS), a condition that can cause neuropsychological regression. In 10 children between 6 and 9 years of age with epilepsy with CSWS or related disorders, we investigated HFOs in scalp EEG spikes during slow-wave sleep through temporal expansion of the EEG traces with a low-cut frequency filter at 70 Hz as well as through time-frequency power spectral analysis. HFOs (ripples) concurrent with spikes were detected in the temporally expanded traces, and the frequency of the high-frequency peak with the greatest power in each patient's spectra ranged from 97.7 to 140.6 Hz. This is the first report on the detection of HFOs from scalp EEG recordings in epileptic patients. We speculate that epileptic HFOs may interfere with higher brain functions in epilepsy with CSWS.

Spectral analysis of EEG gamma rhythms associated with tonic seizures in Lennox-Gastaut syndrome.

PURPOSE: EEG gamma rhythms, which are found in association with epileptic spasms in infants with West syndrome, were explored in the ictal EEGs of tonic seizures in older patients with Lennox-Gastaut syndrome (LGS) to investigate the pathophysiology of the disease. METHODS: The subjects were 20 patients with LGS (11 males, 9 females; age range: 3 years 1 month to 29 years 3 months) who had at least one digitally recorded tonic seizure with minimal artifacts. A time-frequency analysis was applied to each patient's ictal EEG data. RESULTS: A total of 54 seizures were analyzed, excluding spasms in clusters. The ictal EEGs of the tonic seizures showed only diffuse desynchronization in 10 seizures, and desynchronization followed by rhythmic activity in 21. The ictal discharges started as rhythmic activity of varying amplitude without initial desynchronization in 23 seizures. In a total of 25 seizures from 13 patients, gamma rhythms with frequencies ranging from 43 to 101.6Hz were detected by temporal expansion of the ictal EEG traces and spectral analysis. In 24 (96%) of these seizures, gamma rhythms were observed at seizure onset corresponding to visually identified desynchronization. In the remaining seizure, gamma rhythms were found in association with transient suppression of high-amplitude rapid discharges. CONCLUSION: The detection of gamma rhythms in the ictal EEGs of tonic seizures indicated that some tonic seizures might have generative mechanisms in common with epileptic spasms, and that these mechanisms are possibly related to desynchronization at seizure onset.

Spectral characteristics of EEG gamma rhythms associated with epileptic spasms.

To elucidate the pathophysiology of epileptic spasms, unaveraged time-frequency spectra of spasm-associated EEG gamma rhythms were investigated in 15 patients with West syndrome or related disorders. Using these unaveraged spectra, we were able to investigate in detail various aspects of the structure of ictal gamma rhythms that could not be examined using averaged spectra. The characteristics of the ictal gamma peaks (peak frequency, power, duration, and the number of peaks in each brain-region for each spasm) were statistically evaluated with respect to their differences among the brain regions and over the time-course of the clusters. Our findings were as follows: (1) Gamma peaks were clearly detected in most spectra and generally had a similar pattern in each spasm, which repeated in clusters. (2) The mean frequency of gamma peaks was 69.2+/-16.8Hz, and the number of peaks in each brain region of each spasm was 1.83+/-1.16. (3) The occipitoparietal gamma peaks had significantly greater power and longer duration than the frontocentral peaks. (4) The frequency of the gamma peaks was higher in the mid phase of clusters than in the ending, and it tended to have a positive correlation with its latency from the preceding beta peak. An analysis of the ictal gamma rhythms might give some insight into the generative mechanism of spasms.

Rasmussen encephalitis associated with SCN 1 A mutation.

Mutations in the SCN 1 A gene, encoding the neuronal voltage-gated sodium channel alpha1 subunit, cause SMEI, GEFS+, and related epileptic syndromes. We herein report the R1575C-SCN 1 A mutation identified in a patient with Rasmussen encephalitis. R1575C were constructed in a recombinant human SCN 1 A and then heterologously expressed in HEK293 cells along with the human beta1 and beta2 sodium channel accessory subunits. Whole-cell patch-clamp recording was used to define biophysical properties. The R1575C channels exhibited increased channel availability and an increased persistent sodium current in comparison to the wild-type. These defects of electrophysiological properties can result in neuronal hyperexitability. The seizure susceptibility allele may influence the pathogenesis of Rasmussen encephalitis in this case.

Epilepsy development in infancy with epileptic discharges.

As a part of the study to prevent West syndrome (WS) by early treatment, we assessed what kind of epilepsy developed in infants who showed epileptic discharges in early infancy. EEG examinations were performed on 116 infants born from 1997 to September 2004, both before and after 3 months of corrected age (CA). We divided 45 infants who showed epileptic discharges in early infancy into two groups according to the existence of periventricular leukomalacia (PVL) and retrospectively performed the course observation at the survey point on April 1 in 2005. Out of 45 infants showing epileptic discharges in early infancy, 26 developed WS. Compared with infants without PVL, infants with PVL were more likely to develop WS than infants without PVL. Furthermore, infants with PVL were more likely to develop WS than other types of epilepsy. Namely, 11 out of 17 infants with PVL developed WS at the survey point. All infants with WS showed initial epileptic discharges before 5 months of corrected age (CA), and most of them (except for five) had initial epileptic discharges before 3 months of CA. There were two infants who once developed hypsarrhythmia on EEG; however, after starting VPA therapy, they did not develop WS with the improvement of EEG findings, and one was presented here in detail. We proposed that preterm infants with PVL who showed epileptic discharges before 3 months of CA should be treated by antiepileptic drugs to prevent the onset of WS syndrome.