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.

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.

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.