Changes in interhemispheric coherence after total corpus callosotomy: a scalp EEG study in children with non-lesional generalized epilepsy.

PURPOSE: Coherence analysis in electroencephalography (EEG) allows measurement of the degree of consistency of amplitude between pairs of electrodes. Theoretically, disconnective epilepsy surgery should decrease coherence between corresponding areas. The study aimed to evaluate postoperative changes in interhemispheric coherence values after corpus callosotomy (CC). METHODS: Non-lesional, drug-resistant, generalized epilepsy patients who underwent total CC were retrospectively collected. To evaluate coherence, we divided the scalp interictal EEG into "baseline" and "discharge" states after excluding periods with artifacts. Interhemispheric coherence values were obtained between eight pairs of symmetrically opposite scalp electrodes in six different frequency bands. We analyzed both pre- and postoperative EEG sessions and calculated the percentage of difference (POD) in coherence values. RESULTS: We collected 13 patients and analyzed 2496 interhemispheric coherence values. Preoperative coherence values differed significantly between baseline and discharge states (p = 0.0003), but postoperative values did not (p = 0.11). For baseline state, coherence values were decreased after CC and median POD was - 22.3% (p < 0.0001). Delta frequency showed the most decreased POD (-44.3%, p = 0.0009). Median POD was lowest in the Fp1-Fp2 pair of electrodes. For discharge state, coherence values were decreased after CC and median POD was - 24.7% (p < 0.0001). Delta frequency again showed the most decreased POD (-55.9%, p = 0.0016). Median POD was lowest in the F7-F8 pair. CONCLUSION: After total CC, interhemispheric coherence decreased significantly in both baseline and discharge states. The most decreased frequency band was the delta band, which may be used as a representative frequency band in future studies.

[A case of West syndrome with a deletion at chromosome 2q24.3-q31.3].

A male infant suffered from partial seizures at four months of age, and developed West syndrome at eight months of age. ACTH therapy was effective for the West syndrome. However, partial seizures recurred at 14 months of age, which could not be sufficiently controlled with an anti-epileptic drug. A characteristic facial appearance, great toe abnormalities, and developmental retardation were noted. An interstitial deletion of 2q was detected by chromosomal G-banding and array comparative genomic hybridization (CGH) confirmed the deletion as arr 2q24.3q31.3 (166,303,447-180,982.972) ×1 (build19). He presented with clinical findings similar to those of the recently defined 2q31.1 deletion syndrome. The deletion extended to the SCN1A gene, a gene responsible for Dravet syndrome, mapped to the 2q24.3 region. No deletion was noted in the adjacent SCN2A gene. Thus, for interstitial deletions, detailed breakpoints should be identified by array CGH. The frequency of epilepsy varies with deletion ranges in the 2q24-q31 region, suggesting that deletions in the SCN1A gene deletion, as well as in the 2q31.1 region, are involved in the development of West syndrome.

Detecting copy-number variations in whole-exome sequencing data using the eXome Hidden Markov Model: an 'exome-first' approach.

Whole-exome sequencing (WES) is becoming a standard tool for detecting nucleotide changes, and determining whether WES data can be used for the detection of copy-number variations (CNVs) is of interest. To date, several algorithms have been developed for such analyses, although verification is needed to establish if they fit well for the appropriate purpose, depending on the characteristics of each algorithm. Here, we performed WES CNV analysis using the eXome Hidden Markov Model (XHMM). We validated its performance using 27 rare CNVs previously identified by microarray as positive controls, finding that the detection rate was 59%, or higher (89%) with three or more targets. XHMM can be effectively used, especially for the detection of >200 kb CNVs. XHMM may be useful for deletion breakpoint detection. Next, we applied XHMM to genetically unsolved patients, demonstrating successful identification of pathogenic CNVs: 1.5-1.9-Mb deletions involving NSD1 in patients with unknown overgrowth syndrome leading to the diagnosis of Sotos syndrome, and 6.4-Mb duplication involving MECP2 in affected brothers with late-onset spasm and progressive cerebral/cerebellar atrophy confirming the clinical suspect of MECP2 duplication syndrome. The possibility of an 'exome-first' approach for clinical genetic investigation may be considered to save the cost of multiple investigations.

[Clinical evaluation of six patients with anti-NMDAR encephalitis].

OBJECTIVE: We examined the clinical course and the prognosis of patients with anti-NMDAR encephalitis. METHODS: We retrospectively evaluated the patients who has distinctive clinical features as anti-NMDAR encephalitis based on their medical records. RESULTS: There were two male and four female patients with anti-NMDAR encephalitis. They were aged between 13 and 16 years. One of the six, 14 years female patient was negative for anti-NMDAR antibody. All four female patients with anti-NMDAR encephalitis had an ovarian tumor. Neurocognitive dysfunction and epilepsy remained in one female patient with right temporal lobe lesion and one male patient with celebellar abnormalities had mild mental impairment. In three patients including two patients who were examined abdominal MRI for the first time after recovery from the encephalitis, overian tumors became apparent during follow-up. In one of other patients, overian tumors had a tendency to increase in size after recovery. CONCLUSION: Sequellae were seen in two cases that have abnormalities in brain MRI. As to ovarian tumor, it was considered to be necessary to checkup pelvic MRI for at least four years after the onset of encephalitis.

Abnormal axonal development and severe epileptic phenotype in Dynamin-1 (DNM1) encephalopathy.

Dynamin-1 (DNM1) is involved in synaptic vesicle recycling, and DNM1 mutations can lead to developmental and epileptic encephalopathy. The neuroimaging of DNM1 encephalopathy has not been reported in detail. We describe a severe phenotype of DNM1 encephalopathy showing characteristic neuroradiological features. In addition, we reviewed previously reported cases who have DNM1 pathogenic variants with white matter abnormalities. Our case presented drug-resistant seizures from 1 month of age and epileptic spasms at 2 years of age. Brain MRI showed no progression of myelination, progression of diffuse cerebral atrophy, and a thin corpus callosum. Proton magnetic resonance spectroscopy showed a decreased N-acetylaspartate peak and diffusion tensor imaging presented with less pyramidal decussation. Whole-exome sequencing revealed a recurrent de novo heterozygous variant of DNM1. So far, more than 50 cases of DNM1 encephalopathy have been reported. Among these patients, delayed myelination occurred in two cases of GTPase-domain DNM1 encephalopathy and in six cases of middle-domain DNM1 encephalopathy. The neuroimaging findings in this case suggest inadequate axonal development. DNM1 is involved in the release of synaptic vesicles with the inhibitory transmitter GABA, suggesting that GABAergic neuron dysfunction is the mechanism of refractory epilepsy in DNM1 encephalopathy. GABA-mediated signaling mechanisms play important roles in axonal development and GABAergic neuron dysfunction may be cause of white matter abnormalities in DNM1 encephalopathy.

Preoperative interhemispheric coherence as a potential predictive marker for seizure outcome after total corpus callosotomy in nonlesional generalized epilepsy: a scalp EEG study.

OBJECTIVE: Corpus callosotomy (CC) is one of the palliative epilepsy surgical procedures available for nonlesional generalized epilepsy, but it is more invasive than other palliative surgical procedures. The main challenge is proper selection of suitable patients for CC. Coherence analysis is a method for evaluating brain connectivity, but the correlation between preoperative coherence and surgical outcomes has not previously been clarified. The authors aimed to evaluate correlations between preoperative interhemispheric coherence and surgical outcome in patients with nonlesional generalized epilepsy. METHODS: This retrospective study investigated patients with nonlesional generalized epilepsy who underwent total CC. The authors collected data for patients with good seizure outcome (Oguni classification A or B) and bad seizure outcome (Oguni classification D). For coherence analysis, the authors selected a period without interictal discharges. Preoperative interhemispheric coherence values from 8 pairs of symmetrically opposite scalp electrodes were computed across 5 frequency bands. Then, the authors evaluated correlations between coherence and surgical outcomes. RESULTS: Forty patients were included (19 males and 21 females). The mean (range) age at the time of surgery was 5.1 (1-18) years. Seizure outcomes were good in 15 patients and bad in the other 25 patients. Age at onset of epilepsy, duration of epilepsy before surgery, age at time of surgery, and presence of epileptic spasm did not differ significantly between patients with good and bad seizure outcomes (p = 0.36, p = 0.14, p = 0.10, and p = 0.20, respectively). Significant correlations were identified between higher Fp1-Fp2 interhemispheric coherence values in the delta, theta, and alpha frequency bands and bad surgical outcomes (p = 0.0397, p = 0.0322, and p = 0.0476, respectively). The receiver operating characteristic curves of the Fp1-Fp2 coherence values in these frequency bands showed areas under the curve of 67%, 69%, and 67%, respectively. The optimal cutoff values for Fp1-Fp2 interhemispheric coherence to predict surgical outcomes were 55.6 for delta (66.7% sensitivity and 72.0% specificity), 55.9 for theta (60.0% sensitivity and 76.0% specificity), and 50.3 for alpha (53.3% sensitivity and 84.0% specificity). CONCLUSIONS: This is the first study to identify potential predictive factors for surgical outcomes based on preoperative interhemispheric coherence in nonlesional generalized epilepsy. Higher coherence between Fp1-Fp2 in the delta, theta, and alpha frequencies correlated with bad seizure outcome after CC.

Characteristics of malignant brain tumor-associated epileptic spasms.

Although epilepsy is the most common comorbidity of brain tumors, epileptic spasms rarely occur. Brain tumors associated with epileptic spasms are mostly low-grade gliomas. To date, few studies in the literature have reported on malignant (Grades 3-4) brain tumors associated with epileptic spasms. Thus, we aimed to investigate the characteristics of malignant brain tumor-associated epileptic spasms. We retrospectively reviewed patients with malignant brain tumors and epileptic spasms in our institution. Data on demographics, tumor histology, magnetic resonance imaging, epileptic spasm characteristics, electroencephalography, and treatment responsiveness were also collected. Six patients were included. In all cases, the brain tumors occurred in infancy in the supratentorial region and epileptic spasm onset occurred after the completion of brain tumor treatment. Anti-seizure medication did not control epileptic spasms; two patients were seizure-free after epileptic surgery. Although all patients had developmental delays caused by malignant brain tumors and their treatment, developmental regression proceeded after epileptic spasm onset. Two patients who achieved seizure-free status showed improved developmental outcomes after cessation of epileptic spasms. This is the first report of the characteristics of malignant brain tumor-associated epileptic spasms. Our report highlights a difficulties of seizure control and possibillity of efficacy of epileptic surgery in this condition. In malignant brain tumor-associated epileptic spasms, it is important to proceed with presurgical evaluation from an early stage, bearing in mind that epileptic spasms may become drug-resistant.

Higher incidence of acute symptomatic seizures in probable antibody-negative pediatric autoimmune encephalitis than in major antibody-positive autoimmune encephalitis.

Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p < 0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings.

Total callosotomy ameliorates epileptic activity and improves cognitive function in a patient with Miller-Dieker syndrome.

Miller-Dieker syndrome (MDS) is characterized by facial abnormalities and lissencephaly and is caused by a microdeletion in the region containing the LIS1 gene at chromosome 17p13.3. We report a case in which postnatal neuroimaging revealed severe lissencephaly. A 9-month-old boy presented with infantile spasms syndrome. Because of the refractory course of seizures and continued poor vitality, total corpus callosotomy was performed at 28 months of age. Intraoperative electroencephalogram (EEG) showed that the bilateral synchronous epileptiform discharges disappeared immediately after the disconnection. Postoperatively, the epileptic spasms (ES) in clusters disappeared, and single ES followed by focal seizures became the main symptom. The patient smiled more and became more responsive to stimuli. Postoperative scalp interictal EEG showed desynchronized multifocal spike and wave discharges with a marked decrease in the bilateral synchronous spike and wave discharges. Our findings suggest that the corpus callosum is involved in the mechanism ES in clusters in MDS-associated lissencephaly, and total callosotomy could be a therapeutic option.

Location-based selection of the surgical approach to preserve the hippocampus in lesion-associated temporal lobe epilepsy.

BACKGROUND AND OBJECTIVES: Surgical resections for lesions associated with intractable temporal lobe epilepsy (TLE) offers good seizure outcomes.However, the necessity of hippocampectomy in addition to lesionectomy is controversial, especially when the hippocampus is not involved by the lesion. Lesionectomy alone, preserving the hippocampus by an appropriate surgical approach, might offer good seizure outcomes while maintaining neurocognitive function. In the present study, the aims were to examine the surgical strategy for lesions associated with TLE and to present how to select surgical approaches to preserve the hippocampus. METHODS: A total of 22 consecutive lesion-associated TLE patients who underwent lesionectomy alone were retrospectively reviewed. The surgical approach, transsylvian, transorbital, subtemporal, supracerebellar transtentorial, or transcortical approach, was selected based on the location of the lesion. Postoperative seizure outcomes were classified by the Engel classification. Neurocognitive outcomes were assessed before and after surgery if possible. The pathology, the extent of resection, and lesion recurrence were reviewed. RESULTS: The transsylvian approach was selected in six patients, the transorbital approach in one patient, the subtemporal approach in three patients, the supracerebellar transtentorial approach in five patients, and the transcortical approach in seven patients. Eighteen of 22 (81.8 %) patients achieved Engel's class I or II good seizure outcomes. No patients had neurocognitive deterioration after surgery. Twelve patients had various types of brain tumors, and ten patients had non-tumorous lesions. Gross total resection was achieved in 21 patients. All patients had no recurrence. CONCLUSION: For patients with lesion-associated TLE, lesionectomy alone by the appropriate surgical approach offers satisfactory seizure outcomes while preserving hippocampus.

Efficacy and safety of ketamine for pediatric and adolescent super-refractory status epilepticus and the effect of cerebral inflammatory conditions.

OBJECTIVE: To investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology. METHODS: This retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups. RESULTS: The median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8-15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration. CONCLUSIONS: Ketamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.

Comparing late-onset epileptic spasm outcomes after corpus callosotomy and subsequent disconnection surgery between post-encephalitis/encephalopathy and non-encephalitis/encephalopathy.

OBJECTIVE: We aimed to analyze the efficiency of corpus callosotomy (CC) and subsequent disconnection surgeries in patients with late-onset epileptic spasms (LOES) by comparing post-encephalitis/encephalopathy (PE) and non-encephalitis/encephalopathy (NE). We hypothesized these surgeries can control potential focal onset epileptic spasms (ES) in the NE group but not in the PE group. METHODS: We retrospectively included 23 patients (12 with PE and 11 with NE) who initially underwent CC and subsequent disconnection surgeries (five NE). We compared the clinical courses, seizure types, MRI, video-EEG, epilepsy surgery, and seizure outcomes between the two groups. RESULTS: The median age of LOES onset in the PE group was 2.8 (range 1.0-10.1 years) and 2.9 years (range 1.1-12.6) in the NE group. Bilateral MRI abnormalities were observed in both groups (PE, n = 12; NE, n = 3; P < 0.05). The PE group presented ES alone (n = 2), ES + focal seizures (FS) (n = 3), ES + generalized seizures (GS) (n = 3), and ES + FS + GS (n = 4) in addition to stimulus-induced startle seizures (SS) (n = 8) (mean 3.1 seizure types/patient). The NE group presented ES alone (n = 1), ES + FS (n = 2), and ES + FS + GS (n = 8) (mean 2.7 seizure types/patient). In the PE group, CC stopped ES (n = 1) and SS (n = 1) and achieved <50% SS (n = 3). In the NE group, CC achieved immediate ES-free status (n = 2) and < 50% ES (n = 1), and additional disconnection surgeries subsided all seizure types (n = 3) based on lateralized interictal/ictal EEG findings. LOES was significantly remitted by surgery in the NE group (6/11 [55%]) compared with the PE group (1/12 [8%]) (P < 0.05). SIGNIFICANCE: LOES is a drug-resistant, focal/generalized/unknown onset ES. Lateralization of ES in NE could be achieved after CC and eliminated by further disconnection surgeries because of potential focal onset ES. LOES in PE had little benefit from CC for generalized onset ES. However, CC might reduce SS in patients in the PE group with multiple seizure types.

[Clinical study of patients undergoing paperless electroencephalography in emergency room].

Fifty-eight patients who visited the emergency room of our center with febrile convulsions and impaired consciousness, and underwent paperless electroencephalography soon after arrival. They consisted of 25 male and 33 female children, ranging in age from 5 months to 15 years and 4 months, with a mean age of 4 years and 10 months. The final diagnoses were poor responsiveness associated with fever and febrile delirium in 5 patients, febrile convulsions in 26, encephalitis/encephalopathy in 24, convulsions associated with mild gastroenteritis in 2, and aseptic meningitis in 1. The appearance of spindle wave within 24 hours after admission was considered to be a favorable prognostic factor, whereas generalized high-amplitude delta waves without fast-wave components and dysrhythmic flat basic waves were considered poor prognostic factors. We conclude that bed-side paperless electroencephalography is useful for the evaluation of changes in the brain function and course of treatment.

[Usefulness of 123I-iomazenil SPECT in pediatric patients with neurological disease].

This study examined the usefulness of 123I-iomazenil SPECT (IMZ-SPECT), a type of brain scintigram that focuses on the central benzodiazepine receptor in order to determine its distribution and the function of inhibitory neurons. IMZ-SPECT has been used for the detection of epileptogenic foci, especially when surgical intervention is considered. Interictal study by IMZ-SPECT is widely available at numerous institutions and its usefulness has been confirmed in patients with not only focal cortical dysplasia and hippocampal sclerosis, but also tuberous sclerosis and neuronal migration disorders, even when magnetic resonance image fails to demonstrate any abnormal findings. When interpreting scintigrams, the developmental dynamic change of the central benzodiazepine receptor in childhood and the duration of the benzodiazepine exposure period should be taken into consideration. It is expected that IMZ-SPECT will be used in various neurological disorders other than epilepsy in the future allow medical services to be provided based on findings in the inhibitory synaptic system obtained with IMZ-SPECT.

Effect of higher body temperature and acute brain edema on mortality in hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe subtype of acute encephalopathy with a poor prognosis. The factors associated with acute neurological outcomes in patients with HSES remain unclear. This study aimed to determine the clinical features, laboratory and radiological findings, and treatments that determine the acute outcomes of HSES. METHODS: Forty children with HSES registered in a database of Osaka City General Hospital between 1995 and 2020 were included in this observational study. We retrospectively collected data on clinical features, laboratory and radiological items, and treatments. We divided acute neurological outcomes into two groups: the non-death and death groups in 1 week. Correlations were assessed between these items and acute neurological outcomes. RESULTS: Twenty-seven and 13 patients comprised the non-death and death groups, respectively. Univariate logistic regression analysis showed that higher body temperature, presence of hemorrhagic episode, elevated lactate level, high glucose level in the cerebrospinal fluid, and brain edema at initial computed tomography (CT) were correlated with the death group. Regarding treatments, barbiturate therapy, intravenous immunoglobulin, and intravenous methylprednisolone were significantly initiated in the non-death group. The multivariate logistic regression model showed higher body temperature (odds ratio [OR], 4.210 [1.409-12.584]; p = 0.010) and brain edema on initial head CT (OR, 46.917 [3.995-550.976]; p = 0.002) were independent factors. CONCLUSIONS: Higher body temperature and brain edema at the onset of HSES were associated with acute outcomes. The results of this study may be useful for treatment planning and acute outcomes in patients with HSES.

Late relapse of anti-N-methyl-d-aspartate receptor encephalitis with amusia and transiently reduced uptake in 123I-iomazenil single-photon emission computed tomography.

INTRODUCTION: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has a high relapse rate at approximately 10-20%. Most relapses occur within 2 years from onset, and 5 years after onset is rare. We report a case of anti-NMDAR encephalitis relapse with amusia 10 years after the initial encephalitis and discuss the usefulness of 123I-iomazenil single-photon emission computerized tomography (IMZ-SPECT) for its diagnosis. CASE: A 13-year-old left-handed girl presented with a depressed level of consciousness and focal to bilateral tonic-clonic seizures. Cerebrospinal fluid (CSF) analysis showed a mildly increased white blood cell count, elevated neopterin levels, and positive oligoclonal bands. Brain MRI was normal. IMZ-SPECT revealed reduced uptake in the right frontoparietal region. She received intravenous pulse methylprednisolone (IVMP) and high-dose intravenous immunoglobulin for autoimmune encephalitis; her symptoms resolved without neurological deficits. At 23 years old, she had mild right-sided numbness, dysarthria, amusia, and tonic-clonic seizures. Although the CSF analysis and brain MRI were normal, IMZ-SPECT revealed reduced uptake, indicating a relapse of encephalitis. IVMP administration resolved the symptoms. After discharge, the initial and relapse CSF analysis revealed anti-NMDAR antibodies. CONCLUSION: An anti-NMDAR encephalitis relapse 10 years after onset has never been reported. IMZ-SPECT may help in the diagnosis of anti-NMDAR encephalitis.

Longitudinal electroencephalogram findings predict acute neurological and epilepsy outcomes in patients with hemorrhagic shock and encephalopathy syndrome.

OBJECTIVE: Hemorrhagic shock and encephalopathy syndrome (HSES) is a severe subtype of acute encephalopathy with a poor prognosis. The association between electroencephalogram (EEG) findings and neurological outcomes in patients with HSES, including the onset of epilepsy, remains unclear. METHODS: Thirty-two children with HSES registered in a database of Osaka City General Hospital between 2003 and 2018 were included in this study. The EEG findings which consisted of continuity, reactivity, state change, voltage, rhythmic and periodic patterns, and electrographic or electroclinical seizures, in the onset phase were evaluated for patient outcome. Patients who avoided acute death were investigated for epilepsy by a longitudinal EEG. Seizure types were determined by ictal video recordings. RESULTS: We analyzed EEG findings in the onset phase of 30 patients. Severely to extremely abnormal EEG pattern (deteriorated continuity more than discontinuous pattern, presence of generalized abnormal low voltage slow wave, and presence of generalized rhythmic and periodic patterns) in the onset phase correlated with poor outcome (p = 0.0024). Subsequently, 9/23 patients (39%) developed epilepsy, of which a total of eight had epileptic spasms. A significant correlation between interictal epileptic discharges and the development of epilepsy was observed as early as within three months (p = 0.0003). CONCLUSIONS: EEG pattern in the onset phase may be useful to predict the neurological prognosis in the acute stage. Moreover, this study demonstrated that longitudinal EEG findings after the acute phase of HSES were significantly related to the development of epilepsy. EEG findings are useful for predicting acute prognosis and epilepsy in patients with HSES.

A pediatric case of autoimmune glial fibrillary acidic protein astrocytopathy with unique brain imaging patterns and increased cytokines/chemokines.

BACKGROUND: Autoimmune anti-glial fibrillary acidic protein (GFAP) astrocytopathy represents a new spectrum of autoimmune inflammatory central nervous system disorders. In recent years, there have been an increasing number of reports on pediatric patients with this disease other than those in Japan. CASE REPORT: A 6-year-old previously healthy boy presented with fever persisting for approximately 10 days, consciousness disturbance, anorexia, and hyponatremia (Na, 121 mEq/L). Even after appropriate correction of hyponatremia, consciousness disturbance was prolonged and was accompanied by gait disturbance, visual hallucinations, and autonomic dysfunction (bradycardia and urinary dysfunction). On a plain MRI, T2-weighted and fluid-attenuated inversion recovery images showed abnormal hyperintense lesions in the bilateral basal ganglia, thalamus, and periventricular white matter. The cerebrospinal fluid was positive for anti-GFAP antibody before treatment, and cytokines/chemokines were increased. He received three courses of intravenous methylprednisolone, followed by gradually tapered oral prednisolone for 6 months, without relapse after 1 year of observation. CONCLUSION: In cases of autoimmune encephalitis with prolonged consciousness disturbance, hyponatremia, urinary dysfunction, and MRI findings with hyperintensities in the bilateral basal ganglia, thalamus, and periventricular white matter, anti-glial fibrillary acidic protein antibodies should be examined.

Possible critical region associated with late-onset spasms in 17p13.1-p13.2 microdeletion syndrome: a report of two new cases and review of the literature.

17p13.1-2 microdeletion syndrome is a congenital anomaly syndrome with characteristic facial features and multiple malformations. The prevalence of epilepsy with 17p13.1-2 microdeletion is low, with only one case reported for late-onset spasms. Late-onset spasms is one of the rare epilepsy syndromes and one of the developmental epileptic encephalopathies requiring urgent treatment. We experienced two cases of 17p13.1-2 microdeletion syndrome, one of which presented with epileptic spasms in cluster at 18 months of age. EEG showed symmetrical hypsarrhythmia during interictal periods and a paroxysmal fast wave superimposed on widespread slow waves during seizures, leading to the diagnosis of late-onset spasms. Another case had no epilepsy. Comparing the extent of deletion in the two cases with that of previous reports, the involvement of the USP6 gene was suspected. However, the accumulation of additional case reports is needed to confirm the genetic involvement in late-onset spasms.

A case of bilateral limbic and recurrent unilateral cortical encephalitis with anti-myelin oligodendrocyte glycoprotein antibody positivity.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody can be detected not only in acute disseminated encephalomyelitis or optic neuritis but also in limbic or cortical encephalitis. However, no previous reports have demonstrated a relapsing case of these two types of encephalitis. CASE REPORT: An 11-year-old girl presented with fever, headache, abnormal behavior, focal impaired awareness seizures (FIAS) on the left side, and MRI hyperintensities in the bilateral amygdala, hippocampus, and right posterior temporal cortex. The symptoms were alleviated with two courses of intravenous methylprednisolone (IVMP) and one course of immunoglobulin. At 16 years of age, the patient returned with left-sided headache and MRI hyperintensities in the left temporal, parietal, and insular cortices, which improved after 3 courses of IVMP. Oral prednisolone (PSL) was tapered over 6 months, when FIAS reappeared on the right side of the body. MRI showed recurrence in the same regions as in the second episode. She received 3 courses of IVMP, followed by gradually tapered PSL without relapse for 1.5 year. Anti-MOG antibodies were positive in both serum and the cerebrospinal fluid prior to treatment in all three episodes. CONCLUSION: Our results revealed that anti-MOG antibody-related bilateral limbic and unilateral cortical encephalitis can manifest with a variety of phenotypes over time in the same patient.