Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2.

Background and objectives: To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes. Methods: A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge. Results: Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P < 0.01). Discussion: Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.

Acute encephalopathy with biphasic seizures and late reduced diffusion: Predictive EEG findings.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4-6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs. METHODS: We studied the electroencephalograms (EEGs) of children <6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep. RESULTS: The EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035). CONCLUSIONS: EEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.

Splenial Lesions in Benign Convulsions With Gastroenteritis Associated With Rotavirus Infection.

OBJECTIVE: To investigate clinical risk factors for acute magnetic resonance imaging (MRI) abnormalities in patients with benign convulsions with mild gastroenteritis or benign infantile epilepsy. STUDY DESIGN: We investigated clinical and diffusion-weighted imaging findings in 32 patients with benign convulsions with mild gastroenteritis and 22 patients with benign infantile epilepsy who underwent MRI within seven days of seizure onset between 2010 and 2015. RESULTS: Diffusion-weighted imaging showed signal hyperintensity in the splenium of the corpus callosum in seven patients with benign convulsions with mild gastroenteritis, but no abnormalities in patients with benign infantile epilepsy. Patients with benign convulsions with mild gastroenteritis with splenial lesions showed a higher rate of rotavirus detection from feces (P = 0.006), higher serum level of C-reactive protein (P = 0.04), and shorter interval between seizure onset and MRI (P = 0.002) than patients with benign convulsions with mild gastroenteritis without splenial lesions. Multivariate analysis revealed rotavirus infection as a significant risk factor for splenial lesions on diffusion-weighted imaging in patients with benign convulsions with mild gastroenteritis (P = 0.02). CONCLUSIONS: Splenial lesions are often seen during acute period in patients with benign convulsions with mild gastroenteritis. Rotavirus infection is a risk factor for splenial lesions in patients with benign convulsions with mild gastroenteritis, suggesting the role of rotavirus to cause edema in the corpus callosum. From our observations, benign convulsions with mild gastroenteritis with a splenial lesion on diffusion-weighted imaging suggests good outcomes, and extensive evaluation of these patients may be unnecessary.

The effects of co-medications on lamotrigine clearance in Japanese children with epilepsy.

PURPOSE: Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy. METHODS: A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)). RESULTS: The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration. CONCLUSION: LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range.

Manifestations and characteristics of congenital adrenal hyperplasia-associated encephalopathy.

BACKGROUND: This study aimed to clarify the characteristics of acute encephalopathic episodes in patients with congenital adrenal hyperplasia (CAH), which we termed "CAH-associated encephalopathy (CAHE)." METHODS: This retrospective study was conducted using a questionnaire as a nationwide survey of patients with CAH with acute encephalopathy and related episodes. RESULTS: Fifteen patients were recruited on the bases of clinical data that supported a diagnosis of CAHE. Fourteen patients displayed seizures at onset, and 12 patients exhibited refractory seizures. Deep coma lasting >24h was noted in 12 patients. Neuroimaging studies revealed some heterogeneous features. Diffuse or focal edematous lesions in the cerebrum, which produce high signal intensity on diffusion-weighted magnetic resonance imaging or low density on computer tomography, were found in the acute period in all 15 patients. In the chronic period, 14 patients survived, 11 of whom had some degree of neurological sequelae. Moreover, various degrees of cerebral shrinkage were observed in 11 of 14 surviving patients. Surprisingly, there were no abnormal neuroimaging findings in the basal ganglia, brainstem, and cerebellum in any patient. CONCLUSION: Our results indicated that patients with CAH have a risk of developing CAHE, and thus, they should be followed closely because not only status epilepticus or deep coma but also minor symptoms, such as fever and nausea, may lead to CAHE. Because CAHE may feature some heterogeneous encephalopathic episodes, further validation is needed to clarify its etiology.

The magnetic resonance imaging spectrum of Pelizaeus-Merzbacher disease: A multicenter study of 19 patients.

PURPOSE: We retrospectively evaluated the imaging spectrum of Pelizaeus-Merzbacher disease (PMD) in correlation with the clinical course and genetic abnormality. METHODS: We collected the magnetic resonance imaging (MRI) findings of 19 genetically proven PMD patients (all males, aged 0-29years old) using our integrated web-based MRI data collection system from 14 hospitals. The patterns of hypomyelination were determined mainly by the signals of the cerebrum, corticospinal tract, and brainstem on T2-weighted images (T2WI). We assessed the degree of myelination age on T1-weighted images (T1WI) and T2WI independently, and we evaluated cerebellar and callosal atrophy. The clinical severity and genetic abnormalities (causal mutations of the proteolipid protein gene PLP1) were analyzed together with the imaging findings. RESULTS: The clinical stage tended to be more severe when the whole brainstem, or corticospinal tract in the internal capsule showed abnormally high intensity on T2WI. Diffuse T2-high signal of brainstem was observed only in the patients with PLP1 point mutation. Myelination age "before birth" on T1WI is a second manifestation correlated with the clinically severe phenotypes. On the other hand, eight patients whose myelination ages were > 4months on T1WI were associated with mild clinical phenotypes. Four of them showed almost complete myelination on T1WI with a discrepancy in myelination age between T1WI and T2WI. A random and patchy pattern of myelination on T2WI was noted in one patient with PLP1 point mutation. Advanced myelination was observed in three of the seven followed-up patients. Four patients had atrophy of the cerebellum, and 17 patients had atrophy of the corpus callosum. CONCLUSION: Our multicenter study has demonstrated a wide variety of imaging findings of PMD. Signal intensity of brainstem and corticospinal tract of internal capsule would be the points to presume clinical severity in PMD patients. The spectrum of MRI findings should be kept in mind to diagnose PMD and to differentiate from other demyelinating leukodystrophies.

Clinical and neuroimaging findings in children with posterior reversible encephalopathy syndrome.

OBJECTIVE: To clarify the clinical and radiological spectrum of posterior reversible encephalopathy syndrome (PRES) in children, and to identify the prognostic factors. METHODS: The records of 40 children with PRES were reviewed. Acute clinical symptoms, MRI including apparent diffusion coefficient (ADC) maps in the acute and follow-up periods and neurological sequelae, including epilepsy, were noted. RESULTS: Age at onset ranged from 2 to 16 years. Underlying disorders were hematological or neoplastic disorders (n = 20), renal diseases (n = 14) and others (n = 6). In the acute period, 31 patients had seizures, 25 had altered consciousness, 11 had visual disturbances and 10 had headache. Of 29 patients who had ADC maps in the acute period, 13 had reduced diffusivity as shown by ADC within PRES lesions. Of 26 patients with follow-up MRI, 13 had focal gliosis or cortical atrophy. No patients had motor impairment, and four patients had focal epilepsy. No clinical variables were associated with focal gliosis or cortical atrophy on follow-up MRI, but lesional ADC reduction in the acute period was prognostic for focal gliosis or cortical atrophy on follow-up MRI (p = 0.005). CONCLUSIONS: To the best of our knowledge, this is the largest cohort study to date involving PRES in children. Acute symptoms in pediatric patients are similar to those reported in adults, but altered consciousness was more frequent in children. Lesional ADC reduction in the acute period was common and was a good predictor of later, irreversible MRI lesions.

SIL1, a causative cochaperone gene of Marinesco-Söjgren syndrome, plays an essential role in establishing the architecture of the developing cerebral cortex.

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 mutations in abnormal corticogenesis of MSS. SIL1-silencing caused neuronal migration delay during corticogenesis ex vivo. While RNAi-resistant SIL1 rescued the defects, three MSS-causing SIL1 mutants tested did not. These mutants had lower affinities to HSPA5 in vitro, and SIL1-HSPA5 interaction as well as HSPA5 function was found to be crucial for neuronal migration ex vivo. Furthermore time-lapse imaging revealed morphological disorganization associated with abnormal migration of SIL1-deficient neurons. These results suggest that the mutations prevent SIL1 from interacting with and regulating HSPA5, leading to abnormal neuronal morphology and migration. Consistent with this, when SIL1 was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed. Taken together, abnormal neuronal migration and interhemispheric axon development may contribute to MR in MSS.

Genotype-phenotype correlations in alternating hemiplegia of childhood.

OBJECTIVE: Clinical severity of alternating hemiplegia of childhood (AHC) is extremely variable. To investigate genotype-phenotype correlations in AHC, we analyzed the clinical information and ATP1A3 mutations in patients with AHC. METHODS: Thirty-five Japanese patients who were clinically diagnosed with AHC participated in this study. ATP1A3 mutations were analyzed using Sanger sequencing. Detailed clinical information was collected from family members of patients with AHC and clinicians responsible for their care. RESULTS: Gene analysis revealed 33 patients with de novo heterozygous missense mutations of ATP1A3: Glu815Lys in 12 cases (36%), Asp801Asn in 10 cases (30%), and other missense mutations in 11 cases. Clinical information was compared among the Glu815Lys, Asp801Asn, and other mutation groups. Statistical analysis revealed significant differences in the history of neonatal onset, gross motor level, status epilepticus, and respiratory paralysis in the Glu815Lys group compared with the other groups. In addition, 8 patients who did not receive flunarizine had severe motor deteriorations. CONCLUSIONS: The Glu815Lys genotype appears to be associated with the most severe AHC phenotype. Although AHC is not generally seen as a progressive disorder, it should be considered a disorder that deteriorates abruptly or in a stepwise fashion, particularly in patients with the Glu815Lys mutation.

Characteristics of epilepsy occurring in the first four months.

INTRODUCTION: Epilepsies with an onset during the early infantile period are relatively rare and their characteristics are not well recognized. The aim of this study was to determine the clinical characteristics of epilepsies with an onset during the early infantile period. METHODS: Clinical information on 73 patients with the onset of epilepsy within the first four months was collected from hospitals affiliated with Nagoya University. Patients were categorized into three groups: the idiopathic (20 patients), cryptogenic (19 patients), and symptomatic groups (34 patients). RESULTS: Fourteen (70%) of the 20 patients in the idiopathic group, nine (47%) of the 19 patients in the cryptogenic group, and 10 (29%) of the 34 patients in the symptomatic group had their first seizure within the first month of life. All patients in the idiopathic group, 12 patients (63%) in the cryptogenic group, and 18 patients (53%) in the symptomatic group had partial seizures (PS) alone throughout their clinical course. Four patients in the cryptogenic group and nine in the symptomatic group had PS at the onset, but evolved into spasms later. All patients in the idiopathic group, 13 patients (68%) in the cryptogenic group, and 13 patients (38%) in symptomatic group had experienced no seizures for at least one year at the time of the last follow-up. CONCLUSIONS: In patients with non-idiopathic epilepsy, an age-dependent evolution of seizure types was often observed. Recognition of this subgroup of patients could be important for the identification of appropriate candidates for early epilepsy surgery.

[Survival analysis for patients with severe motor and intellectual disabilities following tracheotomy].

To investigate the survival rate and causes of death in patients with severe motor and intellectual disabilities (SMIDs) that necessitated tracheotomy, we retrospectively analyzed 90 patients who underwent tracheotomy between 1990 and 2009. Indications for tracheotomy in these patients were upper airway obstruction (44 patients), recurrent aspiration pneumonia (28 patients), retained secretions (23 patients), prolonged mechanical ventilation (18 patients), chronic respiratory failure (9 patients), central respiratory failure (5 patients), and gastroesophageal reflux (8 patients). Most of the patients underwent tracheotomy at the age of 0-5 years or 10-19 years. As of April 1, 2010, 28 patients had died. The survival rate was 0.91 at 1 year, 0.74 at 5 years, 0.59 at 10 years, 0.54 at 15 years, and 0.40 at 19 years after tracheotomy. Massive tracheal bleeding due to development of tracheo-innominate artery fistulas occurred in 5 patients, and 4 of them died. They were thirteen years of age or older when they underwent tracheotomy, and developed fistulas after 2 weeks or later. In contrast, 7 patients at high risk for fistula formation, including those that had developed severe tracheomalacia associated with granulation or warning hemorrhages, underwent preventive resection of the innominate artery, and all of them had survived. It is important to regularly evaluate patients with SMIDs who have undergone tracheotomy by using bronchofiberscopy to identify risk factors for tracheoinnominate artery fistulas, a preventable cause of death.

A wide spectrum of clinical and brain MRI findings in patients with SLC19A3 mutations.

BACKGROUND: SLC19A3 (solute carrier family 19, member 3) is a thiamin transporter with 12 transmembrane domains. Homozygous or compound heterozygous mutations in SLC19A3 cause two distinct clinical phenotypes, biotin-responsive basal ganglia disease and Wernicke's-like encephalopathy. Biotin and/or thiamin are effective therapies for both diseases. METHODS: We conducted on the detailed clinical, brain MRI and molecular genetic analysis of four Japanese patients in a Japanese pedigree who presented with epileptic spasms in early infancy, severe psychomotor retardation, and characteristic brain MRI findings of progressive brain atrophy and bilateral thalami and basal ganglia lesions. RESULTS: Genome-wide linkage analysis revealed a disease locus at chromosome 2q35-37, which enabled identification of the causative mutation in the gene SLC19A3. A pathogenic homozygous mutation (c.958G > C, [p.E320Q]) in SLC19A3 was identified in all four patients and their parents were heterozygous for the mutation. Administration of a high dose of biotin for one year improved neither the neurological symptoms nor the brain MRI findings in one patient. CONCLUSION: Our cases broaden the phenotypic spectrum of disorders associated with SLC19A3 mutations and highlight the potential benefit of biotin and/or thiamin treatments and the need to assess the clinical efficacy of these treatments.

Prolonged EEG depression in term and near-term infants with hypoxic ischemic encephalopathy and later development of West syndrome.

PURPOSE: This study was performed to clarify the relationship between prolonged depression of electroencephalography (EEG) in term and near-term infants with hypoxic ischemic encephalopathy (HIE) and the later development of West syndrome (WS). METHODS: We investigated 17 term and near-term infants with HIE. Inclusion criteria were as follows: ≥35 weeks of gestation, clinical signs of HIE, magnetic resonance imaging (MRI) lesions corresponding to HIE, assessment of outcome at >18 months of age, depression of EEG, and serial EEG examinations. The 17 infants were divided into the following two groups: Group A (n = 4) with prolonged EEG depression over 21 days of age, and group B (n = 13) with disappearance of EEG depression by 21 days of age. RESULTS: WS developed in all four infants in group A, but in only one of 13 infants in group B. WS occurred significantly more frequently in group A than in group B. For the prediction of subsequent development of WS, prolonged EEG depression over 21 days of age showed sensitivity of 0.80 and specificity of 1.0. In both groups, abnormal irregular faster waves with or without EEG depression were seen in 11 infants between 2 and 28 days of age. They had no significant relationship with WS, but were significantly related to an adverse developmental outcome. CONCLUSIONS: Prolonged depression of EEG over 21 days of age in term or near-term infants with HIE is a valuable predictor of the later development of WS.

Nationwide survey (incidence, clinical course, prognosis) of Rasmussen's encephalitis.

PURPOSE: Rasmussen's encephalitis (RE) is a progressive and catastrophic epileptic disorder caused by chronic localized encephalitis. We performed a nationwide survey of RE to assess the clinical picture, treatment effect, and prognosis of Japanese RE patients. SUBJECTS & METHODS: The subjects were 27 patients (male:12; female:15) from 13 medical facilities. All of them satisfied the clinical and neuroimaging criteria for RE, including 14 pathologically proven cases. RESULTS: They were divided into the childhood-onset rapidly progressive type (CORP, n=19), and late-onset slowly progressive type (LOSP, n=8). The mean age at epilepsy onset was 4 years and 4 months in CORP, and 16 years in LOSP. The mean period between the onset age of epilepsy and development of frequent seizures was 1 year and 4 months in the former, and 3 years and 4 months in the latter. The immunomodulatory treatment including high-dose steroid (n=14) and high-dose intravenous immunoglobulin therapies (IVIgG, n=12) achieved more than a 50% reduction in the seizure frequency in 5 (36%) and 4 (33%) patients, respectively. Eight and seven patients underwent focal cortical resection and functional hemispherectomy, leading to significant improvement in 5 of the 8 patients and excellent seizure control in all 7 patients, respectively. CONCLUSION: Although the high-dose steroid and IVIG therapies may have alleviated the exacerbation of seizures in those with RE, they could not halt the disease progression. Functional hemispherectomy is still the only curative therapy for RE, despite the fact that the early introduction of this procedure remains controversial.

Chronologic changes in neonatal EEG findings in periventricular leukomalacia.

OBJECTIVE: This study sought to clarify chronologic changes in neonatal electroencephalographic (EEG) findings in periventricular leukomalacia (PVL). METHODS: We obtained serial EEG findings for all premature infants who were admitted to our hospital at gestational age of < or =33 weeks between 1997 and 2006. EEG recordings were obtained on days 1 to 4, 5 to 14, 15 to 28, 29 to 56, and 57 to 84. Abnormal EEG findings were classified as acute-stage abnormalities (ASAs) or chronic-stage abnormalities (CSAs) and were subclassified as mild, moderate, or severe. PVL was classified as noncystic, localized cystic, or extensive cystic. The final diagnosis of PVL was made through neurologic assessment and MRI findings at 24 months. RESULTS: Fifty-five infants were diagnosed as having PVL, including 23 with noncystic PVL, 9 with localized cystic PVL, and 23 with extensive cystic PVL. ASAs were observed most frequently on days 1 to 4 and were observed rarely thereafter in all groups. CSAs were observed most frequently on days 5 to 14, were most severe on days 5 to 14, and then resolved within 1 to 2 months in all groups. CSAs in patients with extensive cystic PVL were more severe and persisted longer, compared with other groups. ASA and CSA severity was correlated with PVL severity. CONCLUSIONS: EEG findings in PVL differed according to the severity of PVL and the time of recording. To detect PVL, > or =2 EEG recordings are recommended, 1 within 48 hours after birth, to detect ASAs, and 1 in the second week of life, to detect CSAs.

Callosal lesions and delirious behavior during febrile illness.

We retrospectively reviewed electroencephalography and magnetic resonance imaging findings for 21 children exhibiting delirious behavior during febrile illness. Among these, five patients had transient callosal lesions with or without white matter lesions on diffusion-weighted images. We compared the clinical characteristics, duration, and components of delirious behavior, the duration and severity of reduced consciousness, and EEG findings among patients with or without callosal lesions. No significant differences were detected in these items according to the presence or absence of callosal lesions. Adding insight into the pathogenesis of this condition, our study revealed that callosal lesions are not uncommon in patients exhibiting delirious behavior during febrile illness.

Encephalopathy with a reversible splenial lesion is associated with hyponatremia.

We have encountered several patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) associated hyponatremia. In order to better understand this phenomenon, Na levels were evaluated in a series of patients with MERS. Na was 131.8+/-4.1 mmol/l (mean+/-SD, range 121-140) in 30 patients with MERS; 138.3+/-2.7 mmol/l (range 134-144) in age-matched 21 patients with upper respiratory infection; 136.6+/-2.5 mmol/l (range 132-140) in nine patients with other type of encephalopathy; and 136.2+/-2.6 mmol/l (range 132-140) in 17 patients with febrile seizures. Twenty-five of the thirty patients with MERS had Na<136 mmol/l. There were significant differences between the Na levels of patients with MERS and those with other groups. It is not possible, from the clinical perspective, to completely separate MERS from hyponatremic encephalopathy or to rule out hyponatremia as a contributing factor of MERS.

The spectrum of acute encephalopathy with reduced diffusion in the unilateral hemisphere.

We describe the clinical, EEG, and MRI features of children with reduced diffusion in the unilateral hemispheres. Seven patients with reduced diffusion in the subcortical white matter of the unilateral hemisphere alone were identified. Their median age was 32 months. Human herpesvirus 6 infection was virologically proven in 2 patients and human herpesvirus 7 in 1. The initial neurological symptom was a prolonged seizure in 4, a brief seizure in 2, and delirious behavior in 1. Three patients had biphasic clinical course. Laboratory tests were unremarkable in most patients. MRI showed no abnormal findings during the acute phase, whereas reduced diffusivity in the unilateral hemisphere was seen during the subacute phase. EEG during the acute phase demonstrated marked slowing in the affected hemisphere in 1 patient, mild slowing in 4, and relatively low voltage in 1. No patients died, but 6 patients had various degrees of neurological sequelae. Acute encephalopathy with reduced diffusion in the unilateral hemisphere may be one of the representative phenotypes of acute encephalopathy.

Ictal electroencephalographic findings of neonatal seizures in preterm infants.

The aim of this study is to clarify the characteristics of ictal EEG findings of neonatal seizures in preterm infants. Seizures associated with ictal EEG changes were recognized in nine infants with gestational age of less than 37 weeks. Propagation, migration, shifting, changes in morphology of ictal EEG discharges were evaluated. Seizure manifestation was divided into the following categories; motor seizure, apneic seizure, automatic seizure and seizure without clinical symptoms. The types of the seizures were motor seizures in five infants, apneic in two, automatic in one and those without clinical symptoms in five. All seizures were of focal onset. The foci of seizures were temporal in six infants, occipital in two, central in one, and frontal in one. The morphology of ictal discharges was low voltage spikes or sharp waves in six infants, spikes in two, theta waves in one and high-voltage spiky theta in one. The propagation of ictal discharges was focal in five infants and regional in five. The migration of ictal discharges was observed in two infants and a shift in two. There was no clear relation between seizure manifestation and ictal EEG foci, duration of seizures and morphology or propagation of ictal discharges.