Background: Patients with encephalopathy heralded by a prolonged seizure as the initial symptom often have abnormal subcortical white matter on diffusion-weighted MRI (DWI). Objective: To determine if these patients share other common features. Methods: Patients with encephalopathy heralded by a prolonged seizure and followed by the identification of abnormal subcortical white matter on MRI were collected retrospectively. Their clinical, laboratory, and radiologic data were reviewed. Results: Seventeen patients were identified, ages 10 months to 4 years. All had a prolonged febrile seizure (longer than 1 hour in 12 patients) as their initial symptom. Subsequent seizures, most often in clusters of complex partial seizures, were seen 4 to 6 days after the initial seizure in 16 patients. Outcome ranged from almost normal to severe mental retardation. MRI performed within 2 days of presentation showed no abnormality. Subcortical white matter lesions were observed on DWI between 3 and 9 days in all 17 patients. T2-weighted images showed linear high intensity of subcortical U fibers in 13 patients. The lesions were predominantly frontal or frontoparietal in location with sparing of the perirolandic region. The diffusion abnormality disappeared between days 9 and 25, and cerebral atrophy was detected later than 2 weeks. Three patients having only frontal lesions had relatively good clinical outcome. Conclusions: Although the pathophysiologic mechanism remains unknown, these patients seem to have a distinctive encephalopathy syndrome. MRI is helpful in establishing the diagnosis of this encephalopathy.

Summary: Objective: Multiple tubers in patients with tuberous sclerosis complex (TSC) often are responsible for drug‐resistant epilepsy. The complexity of the epileptic network formed by multiple tubers complicates localization of the epileptogenic zone that is needed to design a surgical treatment strategy. High frequency oscillations (HFOs) on intracranial video‐electroencephalography (IVEEG) may be a valuable surrogate marker for the localization of the epileptogenic zone. The purpose of this study was to test the hypothesis that high occurrence rate (OR) of interictal HFOs can guide the localization of the epileptogenic zone.Methods: We analyzed the OR of interictal HFOs at 80–200 Hz (ripples) and >200 Hz (fast ripples, FRs). We divided OR of interictal HFOs between high and low rates by thresholding. We analyzed the correlation between seizure outcomes using Engel classification and the resection ratio of the seizure onset zone (SOZ), and high‐OR HFOs using ordinal logistic regression analysis.Results: We collected 10 patients. The seizure outcomes resulted in Engel classification I in three patients, II in four, III in one, and IV in two. High‐OR ripples (5–57 [mean 29] channels, 1–4 [2.8] lobes) and high‐OR FRs (9–66 [mean 27] channels, 1–4 [2.6] lobes) were widely distributed. The resection ratio of SOZ did not show statistically significant correlation with the seizure outcome. The resection ratio of high‐OR ripples showed statistically significant correlation with the seizure outcome (p = 0.038). The resection ratio of high‐OR FRs showed statistically significant correlation with the seizure outcome (p = 0.048).Significance: The multiple extensive zones with high‐OR HFOs suggest a complex and widespread epileptic network in patients with TSC. In a subset of TSC patients with drug‐resistant epilepsy, resection of cortex with both interictal high‐OR FRs and ripples on IVEEG correlated with a good seizure outcome.

Purpose: Genetic mutations of the cyclin‐dependent kinase‐like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe‐to‐profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. Methods: A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG‐binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. Key Findings: One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. Significance: We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients.

Summary: Purpose:  The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome.Methods:  Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for >24 h in association with infectious symptoms.Key Findings:  There were seven boys and eight girls. A mutation of the SCN1A gene was present in nine (truncation in six and missense in three). The frequency of seizures during the 3 months before the onset of acute encephalopathy was monthly in seven children and none in three. The median age at the onset of acute encephalopathy was 44 months (range 8–184 months). All children had status epilepticus followed by coma as the initial manifestation. Two different distributions of brain lesions were observed on diffusion‐weighted images during the acute phase: cerebral cortex–dominant lesions with or without deep gray matter involvement and subcortical‐dominant lesions. Four children died; nine survived with severe sequelae, and two had moderate sequelae.Significance:  We must be aware that acute encephalopathy is an important complication in children with Dravet syndrome, and associated with fulminant clinical manifestations and a poor outcome.